本申请是申请日为2006年4月21日、发明名称为“用于犬科动物中呼吸系统疾病控制的物质和方法”的中国专利申请201310335954.3的分案申请。
相关申请的参考
本申请要求2005年4月21日申请的美国临时申请序号60/673,443的优先权,将该临时申请完整(包括任何附图、表、核酸序列、氨基酸序列和图)引入本文作为参考。
发明背景
“狗舍咳嗽”或者感染性气管支气管炎(itb)是狗中的急性、传染性呼吸系统感染,其特征主要是咳嗽(fordetal,1998)。犬itb被认为是世界上狗的最普遍的感染性呼吸系统疾病,并且当狗在高密度群体环境如狗舍中居住时,爆发可以达到流行性比例。多数爆发是由于直接的狗-狗接触或者呼吸系统分泌物的气雾化(fordetal,1998)。临床病征由细菌和病毒的一种或者组合感染引起,所述细菌和病毒可以在上呼吸道和下呼吸道的上皮组织中建群。犬科动物副流感病毒(cpiv)和支气管博德特氏菌(bordetellabronchiseptica)细菌是从受侵袭的狗分离的最常见的生物,但是几种其他病毒,如犬科动物瘟热病毒(cdv)和犬科动物腺病毒-1和-2(cav-1,cav-2),以及细菌如链球菌(streptococcussp.)、pasteurellamulticoda和大肠杆菌(escherichiacoli)可以影响临床过程和结果(fordetal,1998)。尽管在高密度群体中爆发最有效和快速发生,具有高的发病率,但是并发的呼吸系统感染和死亡是不常见的。尽管可以发生威胁生命的继发性细菌性肺炎,但是多数itb病例是自身限制性的并且在没有任何治疗下消退(fordetal,1998)。
在1992年7月,推测为“狗舍咳嗽”的呼吸系统感染在新英格兰(newengland)、佛罗里达(florida)、西弗吉尼亚(westvirginia)、威斯康辛(wisconsin)、堪萨斯(kansas)、科罗拉多(colorado)、俄克拉荷马(oklahoma)和亚利桑那州(arizona)的几个灵
在1998年下半年到1999年上半年,在美国的竞赛灵
在2003年3月-4月,在美国东部的灵
没有公开的报导记载在1992、1998-1999或2003年在竞赛灵
病毒从一个宿主物种传染到另一个是流感病毒的生态学和流行病学的关键特征(webster,1998)。流感病毒的物种间传染的两个基本机制是可能的(websteretal.,1992;lipatovetal.,2004)。一种是基本上未变的病毒从一个物种直接转移到另一个物种。该机制的实例包括最近的家禽流感病毒的h5n1亚型对人的感染(subbaraoetal.,1998;peirisetal.,2004;guanetal.,2004)和可能地1918年的大流行,称作西班牙流感(reidetal.,2004)。第二种机制是流感病毒基因组的区段化性质的结果。用来自不同物种的病毒共感染宿主可以导致区段化病毒基因的重排列,和产生能够感染其他物种的重组体。例如,鸟类和人流感病毒之间基因重排列产生的新的病毒在1957和1968年导致人类流感大流行(websteretal.,1992;lipatovetal.,2004;kawaokaetal.,1989)。
未改变的流感病毒从自然宿主物种向不同物种的多数直接传播是最终事件,因为在新物种的个体之间的持续传播不能发生。多种病毒-宿主相互作用是复制和水平传播所必须的并且为流感病毒在新的宿主中的永续性提供了强大的屏障(webbyetal.,2004)。因此,流感病毒的新的宿主特异性谱系的建立是不常见的并且仅仅在驯养的家禽、猪、马和人类中发生(websteretal.,1992;lipatovetal.,2004)。
因为流感病毒感染的严重性质,所以仍然需要诊断、预防和治疗流感病毒感染的方法。
发明概述
本发明涉及分离的流感病毒,其能够感染犬科动物和在犬科动物中引起呼吸系统疾病。本发明还涉及用于诱导针对本发明的流感病毒的免疫应答的组合物和方法。本发明还涉及用于鉴定本发明的病毒和和诊断本发明的病毒对动物的感染的组合物和方法。
附图简述
本专利或者申请文件含有至少一副彩图。专利局将根据请求和在支付了必要的费用后提供具有彩图的本专利或专利申请公布的拷贝。
图1a-1b显示了血凝素基因之间的系统发生关系。图1a显示了来自代表性犬、人、鸟类、猪和马分离群,包括作为外类群的a/budgerigar/hokkaido/1/77(h4)的ha基因树。图1b显示了使用a/duck/ukraine/63(h3)作为外类群,犬流感病毒ha基因与同一时期的和较老的马ha基因的树。通过近邻连接方法从核苷酸序列推论出系统树并且显示了≥90%的自展分析值。条形表示核苷酸改变数目/水平树枝的单位长度。
图2a-2b显示了在肺中流感h3抗原的免疫组织化学检测。用针对ha血凝素的小鼠单克隆抗体检测肺组织切片并通过免疫过氧化物酶反应检测结合(褐色沉淀)。图2a显示了来自具有自发疾病的灵
图3显示了在死于与流感病毒感染有关的出血性肺炎的灵
图4a-4b显示了在h3血凝素基因中的系统发生关系。图4a显示了犬科动物流感病毒ha基因与同一时期的和较老的马ha基因的系统树。图4b显示了犬科动物流感病毒ha蛋白质与同一时期的和较老的马ha基因的系统树。通过近邻连接方法从基因或者氨基酸序列推论出系统树并且显示了≥80%的自展分析值。条形表示氨基酸改变数目/水平树枝的单位长度。
图5显示了在死于与流感病毒感染有关的肺炎的狗的肺中支气管和支气管腺的上皮细胞中流感病毒h3蛋白质。上图:支气管中纤毛上皮细胞的糜烂。组织用h&e染色。下图:在支气管(左)和支气管腺(右)上皮细胞的细胞质中流感病毒h3蛋白质。将组织用针对流感病毒h3的单克隆抗体染色,通过免疫过氧化物酶反应检测(褐色沉淀)并用苏木精复染。
图6a-6d显示了从扩增10倍连续体外稀释的转录的rna标准得到的h3和基质基因(图6a和图6b)的扩增图。通过起始rna浓度的对数值对从每次稀释得到的阈值循环数(ct)作图,构造h3和基质基因(图6c和图6d)的标准曲线。
图7显示用10倍连续稀释的病毒原种(包括a/wyoming/3/2003和a/canine/fl/242/2003)测试directigenflua的灵敏性。紫色三角形指示阳性结果。
序列简述
seqidno:1是可以根据本发明使用的编码pb2蛋白质的犬科动物流感病毒(florida/43/04)的核苷酸序列。
seqidno:2是seqidno:1编码的氨基酸序列。
seqidno:3是可以根据本发明使用的编码pb1蛋白质的犬科动物流感病毒(florida/43/04)的核苷酸序列。
seqidno:4是seqidno:3编码的氨基酸序列。
seqidno:5是可以根据本发明使用的编码pa蛋白质的犬科动物流感病毒(florida/43/04)的核苷酸序列。
seqidno:6是seqidno:5编码的氨基酸序列。
seqidno:7是可以根据本发明使用的编码ns蛋白质的犬科动物流感病毒(florida/43/04)的核苷酸序列。
seqidno:8是seqidno:7编码的氨基酸序列。
seqidno:9是可以根据本发明使用的编码np蛋白质的犬科动物流感病毒(florida/43/04)的核苷酸序列。
seqidno:10是seqidno:9编码的氨基酸序列。
seqidno:11是可以根据本发明使用的编码na蛋白质的犬科动物流感病毒(florida/43/04)的核苷酸序列。
seqidno:12是seqidno:11编码的氨基酸序列。
seqidno:13是可以根据本发明使用的编码ma蛋白质的犬科动物流感病毒(florida/43/04)的核苷酸序列。
seqidno:14是seqidno:13编码的氨基酸序列。
seqidno:15是可以根据本发明使用的编码ha蛋白质的犬科动物流感病毒(florida/43/04)的核苷酸序列。
seqidno:16是seqidno:15编码的氨基酸序列。
seqidno:17是可以根据本发明使用的编码pb2蛋白质的犬科动物流感病毒(fl/242/03)的核苷酸序列。
seqidno:18是seqidno:17编码的氨基酸序列。
seqidno:19是可以根据本发明使用的编码pb1蛋白质的犬科动物流感病毒(fl/242/03)的核苷酸序列。
seqidno:20是seqidno:19编码的氨基酸序列。
seqidno:21是可以根据本发明使用的编码pa蛋白质的犬科动物流感病毒(fl/242/03)的核苷酸序列。
seqidno:22是seqidno:21编码的氨基酸序列。
seqidno:23是可以根据本发明使用的编码ns蛋白质的犬科动物流感病毒(fl/242/03)的核苷酸序列。
seqidno:24是seqidno:23编码的氨基酸序列。
seqidno:25是可以根据本发明使用的编码np蛋白质的犬科动物流感病毒(fl/242/03)的核苷酸序列。
seqidno:26是seqidno:25编码的氨基酸序列。
seqidno:27是可以根据本发明使用的编码na蛋白质的犬科动物流感病毒(fl/242/03)的核苷酸序列。
seqidno:28是seqidno:27编码的氨基酸序列。
seqidno:29是可以根据本发明使用的编码ma蛋白质的犬科动物流感病毒(fl/242/03)的核苷酸序列。
seqidno:30是seqidno:29编码的氨基酸序列。
seqidno:31是可以根据本发明使用的编码ha蛋白质的犬科动物流感病毒(fl/242/03)的核苷酸序列。
seqidno:32是seqidno:31编码的氨基酸序列。
seqidno:33是seqidno:16中显示的ha蛋白质的成熟形式,其中已经除去了n-末端16个氨基酸的信号序列。
seqidno:34是seqidno:32中显示的ha蛋白质的成熟形式,其中已经除去了n-末端16个氨基酸的信号序列。
seqidno:35是可以根据本发明使用的寡核苷酸。
seqidno:36是可以根据本发明使用的寡核苷酸。
seqidno:37是可以根据本发明使用的寡核苷酸。
seqidno:38是可以根据本发明使用的寡核苷酸。
seqidno:39是可以根据本发明使用的寡核苷酸。
seqidno:40是可以根据本发明使用的寡核苷酸。
seqidno:41是可以根据本发明使用的寡核苷酸。
seqidno:42是可以根据本发明使用的寡核苷酸。
seqidno:43是可以根据本发明使用的寡核苷酸。
seqidno:44是可以根据本发明使用的寡核苷酸。
seqidno:45是可以根据本发明使用的寡核苷酸。
seqidno:46是可以根据本发明使用的寡核苷酸。
seqidno:47是可以根据本发明使用的编码pb2蛋白质的犬科动物流感病毒(miami/2005)的核苷酸序列。
seqidno:48是seqidno:47编码的氨基酸序列。
seqidno:49是可以根据本发明使用的编码pb1蛋白质的犬科动物流感病毒(miami/2005)的核苷酸序列。
seqidno:50是seqidno:49编码的氨基酸序列。
seqidno:51是可以根据本发明使用的编码pa蛋白质的犬科动物流感病毒(miami/2005)的核苷酸序列。
seqidno:52是seqidno:51编码的氨基酸序列。
seqidno:53是可以根据本发明使用的编码ns蛋白质的犬科动物流感病毒(miami/2005)的核苷酸序列。
seqidno:54是seqidno:53编码的氨基酸序列。
seqidno:55是可以根据本发明使用的编码np蛋白质的犬科动物流感病毒(miami/2005)的核苷酸序列。
seqidno:56是seqidno:55编码的氨基酸序列。
seqidno:57是可以根据本发明使用的编码na蛋白质的犬科动物流感病毒(miami/2005)的核苷酸序列。
seqidno:58是seqidno:57编码的氨基酸序列。
seqidno:59是可以根据本发明使用的编码ma蛋白质的犬科动物流感病毒(miami/2005)的核苷酸序列。
seqidno:60是seqidno:59编码的氨基酸序列。
seqidno:61是可以根据本发明使用的编码ha蛋白质的犬科动物流感病毒(miami/2005)的核苷酸序列。
seqidno:62是seqidno:61编码的氨基酸序列。
seqidno:63是可以根据本发明使用的编码pb2蛋白质的犬科动物流感病毒(jacksonville/2005)的核苷酸序列。
seqidno:64是seqidno:63编码的氨基酸序列。
seqidno:65是可以根据本发明使用的编码pb1蛋白质的犬科动物流感病毒(jacksonville/2005)的核苷酸序列。
seqidno:66是seqidno:65编码的氨基酸序列。
seqidno:67是可以根据本发明使用的编码pa蛋白质的犬科动物流感病毒(jacksonville/2005)的核苷酸序列。
seqidno:68是seqidno:67编码的氨基酸序列。
seqidno:69是可以根据本发明使用的编码ns蛋白质的犬科动物流感病毒(jacksonville/2005)的核苷酸序列。
seqidno:70是seqidno:69编码的氨基酸序列。
seqidno:71是可以根据本发明使用的编码np蛋白质的犬科动物流感病毒(jacksonville/2005)的核苷酸序列。
seqidno:72是seqidno:71编码的氨基酸序列。
seqidno:73是可以根据本发明使用的编码na蛋白质的犬科动物流感病毒(jacksonville/2005)的核苷酸序列。
seqidno:74是seqidno:73编码的氨基酸序列。
seqidno:75是可以根据本发明使用的编码ma蛋白质的犬科动物流感病毒(jacksonville/2005)的核苷酸序列。
seqidno:76是seqidno:75编码的氨基酸序列。
seqidno:77是可以根据本发明使用的编码ha蛋白质的犬科动物流感病毒(jacksonville/2005)的核苷酸序列。
seqidno:78是seqidno:77编码的氨基酸序列。
seqidno:79是可以根据本发明使用的寡核苷酸。
seqidno:80是可以根据本发明使用的寡核苷酸。
seqidno:81是可以根据本发明使用的寡核苷酸。
seqidno:82是可以根据本发明使用的寡核苷酸。
seqidno:83是可以根据本发明使用的寡核苷酸。
seqidno:84是可以根据本发明使用的寡核苷酸。
seqidno:85是可以根据本发明使用的寡核苷酸。
seqidno:86是可以根据本发明使用的寡核苷酸。
seqidno:87是可以根据本发明使用的寡核苷酸。
seqidno:88是可以根据本发明使用的寡核苷酸。
发明详述
本发明涉及分离的流感病毒,其能够感染犬科动物和引起呼吸系统疾病。在一个实施方案中,本发明的流感病毒包含编码具有seqidno:2、4、6、8、10、12、14、16、18、20、22、24、26、28、30、32、33、34、48、50、52、54、56、58、60、62、64、66、68、70、72、74、76或78任一个所示的氨基酸序列的蛋白质或者其功能和/或免疫原性片段或者变体的多核苷酸。在一个特定实施方案中,所述多核苷酸包含seqidno:1、3、5、7、9、11、13、15、17、19、21、23、25、27、29、31、47、49、51、53、55、57、59、61、63、65、67、69、71、73、75或77中任一个所示的核苷酸序列,或者其片段或者变体。在特定实施方案中,本发明的流感病毒是亚型h3。根据本文描述的方法,可以从受感染的狗分离病毒并在细胞或者蛋中培养。在示例的实施方案中,流感病毒是甲型流感病毒。
本发明还涉及包含本发明的流感病毒的一种或多种基因或者基因组区段的全部或者部分的多核苷酸。在一个实施方案中,本发明的多核苷酸包含流感血凝素(ha)基因、神经氨酸酶(na)基因、核蛋白(np)基因、基质蛋白(ma或者m)基因、聚合酶碱性(pb)蛋白基因、聚合酶酸性(pa)蛋白基因、非结构(ns)蛋白基因,或者这些基因任一种的功能片段或者变体。在特定实施方案中,本发明的多核苷酸包含血凝素(ha)基因或者其功能片段或者变体。在另一实施方案中,ha基因编码血凝素蛋白质,其与马h3共有序列的氨基酸序列相比,具有如下一个或多个:83位的丝氨酸;222位的亮氨酸;328位的苏氨酸;和/或483位的苏氨酸。在一个实施方案中,ha基因编码具有seqidno:16、32、62或78中所示的氨基酸序列的多肽,或者其功能和/或免疫原性片段或者变体。在一个特定实施方案中,ha基因包含seqidno:15、31、61或77中所示的核苷酸序列。
在一个实施方案中,本发明的多核苷酸编码具有seqidno:2、4、6、8、10、12、14、16、18、20、22、24、26、28、30、32、33、34、48、50、52、54、56、58、60、62、64、66、68、70、72、74、76或78的任一个中所示的氨基酸序列的多肽,或者其功能和/或免疫原性片段或者变体。在特定实施方案中,编码seqidno:2、4、6、8、10、12、14、16、18、20、22、24、26、28、30、32、33、34、48、50、52、54、56、58、60、62、64、66、68、70、72、74、76或78中所示的氨基酸序列的多核苷酸分别包含seqidno:1、3、5、7、9、11、13、15、17、19、21、23、25、27、29、31、47、49、51、53、55、57、59、61、63、65、67、69、71、73、75或77中所示的核苷酸序列,或者编码seqidno:2、4、6、8、10、12、14、16、18、20、22、24、26、28、30、32、33、34、48、50、52、54、56、58、60、62、64、66、68、70、72、74、76或78的任一项的功能和/或免疫原性片段或者变体的序列。从而,本发明涉及多核苷酸序列,其包含seqidno:1、3、5、7、9、11、13、15、17、19、21、23、25、27、29、31、47、49、51、53、55、57、59、61、63、65、67、69、71、73、75或77的任一项中所示的核苷酸序列,或者seqidno:1、3、5、7、9、11、13、15、17、19、21、23、25、27、29、31、47、49、51、53、55、57、59、61、63、65、67、69、71、73、75或77的任一项的片段或者变体,包括简并变体。在一个特定实施方案中,本发明的多核苷酸可以包含:seqidno:3的核苷酸1-2271;seqidno:5的核苷酸1-2148;seqidno:7的核苷酸1-657;seqidno:9的核苷酸1-1494;seqidno:11的核苷酸1-1410;seqidno:13的核苷酸1-756;seqidno:15的核苷酸1-1695;seqidno:19的核苷酸1-2271;seqidno:21的核苷酸1-2148;seqidno:23的核苷酸1-657;seqidno:25的核苷酸1-1494;seqidno:29的核苷酸1-756;seqidno:31的核苷酸1-1695;seqidno:47的核苷酸1-2277;seqidno:49的核苷酸1-2271;seqidno:51的核苷酸1-2148;seqidno:53的核苷酸1-690;seqidno:55的核苷酸1-1494;seqidno:57的核苷酸1-1410;seqidno:59的核苷酸1-756;seqidno:61的核苷酸1-1695;seqidno:63的核苷酸1-2277;seqidno:65的核苷酸1-2271;seqidno:67的核苷酸1-2148;seqidno:69的核苷酸1-690;seqidno:71的核苷酸1-1494;seqidno:73的核苷酸1-1410;seqidno:75的核苷酸1-756;和seqidno:77的核苷酸1-1695。在本发明的范围内预期的病毒多核苷酸和多肽序列的核苷酸和氨基酸序列已经保存在genbank,检索号为dq124147到dq124161和dq124190,将其公开引入本文作为参考。
本发明还涉及本发明的流感病毒的多核苷酸编码的多肽。本发明还涉及主题多肽的功能和/或免疫原性片段和变体。预期的多肽包括本发明的流感病毒的ha蛋白、na蛋白、ns蛋白、核蛋白、聚合酶碱性蛋白、聚合酶酸性蛋白,和基质蛋白。在一个示例的实施方案中,本发明的多肽具有seqidno:2、4、6、8、10、12、14、16、18、20、22、24、26、28、30、32、33、34、48、50、52、54、56、58、60、62、64、66、68、70、72、74、76或78任一项所示的氨基酸序列,或者其功能和/或免疫原性片段或变体。
本发明还涉及包含本发明的多核苷酸序列的多核苷酸表达构建体。在一个实施方案中,本发明的表达构建体包含多核苷酸序列,该多核苷酸序列编码包含seqidno:2、4、6、8、10、12、14、16、18、20、22、24、26、28、30、32、33、34、48、50、52、54、56、58、60、62、64、66、68、70、72、74、76或78任一项所示的氨基酸序列的多肽,或者其功能和/或免疫原性片段或变体。在特定实施方案中,编码seqidno:2、4、6、8、10、12、14、16、18、20、22、24、26、28、30、32、33、34、48、50、52、54、56、58、60、62、64、66、68、70、72、74、76或78中所示的氨基酸序列的多核苷酸分别包含seqidno:1、3、5、7、9、11、13、15、17、19、21、23、25、27、29、31、47、49、51、53、55、57、59、61、63、65、67、69、71、73、75或77的任一个中所示的核苷酸序列,或者编码seqidno:2、4、6、8、10、12、14、16、18、20、22、24、26、28、30、32、33、34、48、50、52、54、56、58、60、62、64、66、68、70、72、74、76或78任一个的功能和/或免疫原性片段或变体的序列。从而,本发明涉及包含多核苷酸序列的表达构建体,所述多核苷酸序列包含seqidno:1、3、5、7、9、11、13、15、17、19、21、23、25、27、29、31、47、49、51、53、55、57、59、61、63、65、67、69、71、73、75或77的任一个中所示的核苷酸序列,或者seqidno:1、3、5、7、9、11、13、15、17、19、21、23、25、27、29、31、47、49、51、53、55、57、59、61、63、65、67、69、71、73、75或77任一个的片段或者变体,包括简并变体。在优选实施方案中,本发明的表达构建体提供了本发明的有效连接的多核苷酸的过表达。
本发明的表达构建体一般包括在预计的宿主细胞中有功能的调节元件,在所述宿主细胞中将表达该表达构建体。从而,本领域技术人员可以选择用于例如人类宿主细胞、哺乳动物宿主细胞、昆虫宿主细胞、酵母宿主细胞、细菌宿主细胞、和植物宿主细胞的调节元件。在一个实施方案中,调节元件是在犬科动物细胞中有功能的调节元件。调节元件包括启动子、转录终止序列、翻译终止序列、增强子、和多聚腺苷酸化元件。如本文所用的,术语“表达构建体”指核酸序列的组合,其提供了有效连接的核酸序列的转录。如本文所用的,术语“有效连接”指所述的元件的并列,其中所述元件处于允许它们以它们预期的方式发挥功能的关系中。通常,有效连接的元件为邻接的关系。
本发明的表达构建体可以包含有效连接到编码本发明多肽的多核苷酸序列的启动子序列。使用本领域中已知的标准技术,可以将启动子掺入多核苷酸中。在本发明的表达构建体中可以使用启动子的多个拷贝或者多个启动子。在优选实施方案中,启动子与表达构建体中转录起始位点的距离可以与它与天然遗传环境中转录起始位点的距离相同。在该距离中允许一定的变化而不实质性降低启动子活性。在表达构建体中通常包括转录起始位点。优选地,与本发明的表达构建体结合的启动子提供了本发明的有效连接的多核苷酸的过表达。
与本发明的表达构建体用于真核细胞中的启动子可以是病毒或者细菌来源的。病毒启动子包括,但不限于,巨细胞病毒(cmv)基因启动子、sv40早期或者晚期启动子,或者劳斯肉瘤病毒(rsv)基因启动子。细胞来源的启动子包括,但不限于,结蛋白基因启动子和肌动蛋白基因启动子。适于与本发明的表达构建体用于酵母细胞的启动子包括,但不限于,3-磷酸甘油酸酯激酶启动子、甘油醛-3-磷酸脱氢酶启动子、金属硫蛋白启动子、醇脱氢酶-2启动子,和己糖激酶启动子。
如果在植物细胞中提供或者向植物细胞中导入表达构建体,那么可以使用植物病毒启动子,如花椰菜花叶病毒(camv)35s(包括增强的camv35s启动子(见,例如,美国专利号5,106,739和an,1997))或者camv19s启动子。可以用于植物中表达构建体的其他启动子包括,例如,prolifera启动子、ap3启动子、热休克启动子、根癌农杆菌(a.tumefaciens)的t-dna1'-或2'-启动子、多聚半乳糖醛酸酶启动子、来自牵牛花的查耳酮合酶a(chs-a)启动子、烟草pr-1a启动子、泛蛋白启动子、肌动蛋白启动子、alca基因启动子、pin2启动子(xuetal.,1993)、玉米wipi启动子、玉米trpa基因启动子(美国专利号5,625,136)、玉米cdpk基因启动子、和rubiscossu启动子(美国专利号5,034,322)。根特异的启动子,如美国专利号6,455,760或美国专利号6,696,623或公布的美国专利申请号20040078841;20040067506;20040019934;20030177536;20030084486;或20040123349中描述的任一种启动子序列可以用于本发明的表达构建体。组成性启动子(如camv、泛蛋白、肌动蛋白或者nos启动子)、发育调节的启动子和诱导型启动子(如可以通过热、光、激素或者化学品诱导的那些启动子)也预期用于本发明的多核苷酸表达构建体。也可以使用组织特异性启动子,例如,果实特异性启动子,如番茄的e8启动子(检索号:af515784;goodetal.(1994))。也可以使用种子特异性启动子,如来自β-菜豆蛋白基因(例如,菜豆的)或者大豆球蛋白基因(例如,大豆的)的启动子,和其他启动子。
对于在原核系统中表达,本发明的表达构建体可以包含启动子,如碱性磷酸酶启动子、色氨酸(trp)启动子、λpl启动子、β-内酰胺酶启动子、乳糖启动子、phoa启动子、t3启动子、t7启动子、或者tac启动子(deboeretal.,1983)。
本发明的表达构建体可以任选含有转录终止序列、翻译终止序列、编码信号肽的序列,和/或增强子元件。转录终止区可以通常从真核生物或者病毒基因序列的3’非翻译区得到。转录终止序列可以位于编码区的下游以提供有效终止。信号肽序列是通常存在于蛋白质的氨基末端的短氨基酸序列,其负责有效连接的成熟多肽重定位到多种不同的翻译后细胞目的地,从特定细胞器隔室到蛋白质作用部位和细胞外环境。通过使用有效连接的信号肽序列将基因产物靶向预期的细胞和/或细胞外目的地预期用于本发明的多肽。典型的增强子是顺式作用元件,其增加基因转录并且可以包括在表达构建体中。典型的增强子元件是本领域中已知的,并且包括,但不限于,camv35s增强子元件、巨细胞病毒(cmv)早期启动子增强子元件,和sv40增强子元件。增强基因表达的内含子介导的增强子元件也是本领域中已知的。这些元件必须存在于转录区内并且是方向依赖性的。
指导从表达构建体转录的mrna的多聚腺苷酸化的dna序列也可以包括在表达构建体中,并且包括,但不限于,章鱼碱合酶或者胭脂氨酸合酶信号。
表达构建体还可以包括一种或多种显性选择标记基因,包括,例如,编码抗生素抗性和/或除草剂抗性用于选择转化细胞的基因。抗生素抗性基因可以提供对一种或多种下面的抗生素的抗性:潮霉素、卡那霉素、博来霉素、g418、链霉素、巴龙霉素、新霉素和大观霉素。通过新霉素磷酸转移酶(nptii)可以提供卡那霉素抗性。除草剂抗性基因可以提供对膦丝菌素乙酰转移酶或者草甘膦的抗性。用于细胞转化筛选的其他标记包括,但不限于,编码β-葡糖醛酸糖苷酶(gus)、β-半乳糖苷酶、萤光素酶、胭脂氨酸合成酶、氯霉素乙酰转移酶(cat)、绿色荧光蛋白(gfp)或者增强的gfp的基因(yangetal.,1996)。
本发明还涉及包含编码本发明多肽的本发明的多核苷酸序列的多核苷酸载体。可以在本发明的表达构建体或者多核苷酸的5’和3’末端包括独特的限制酶位点以允许插入到多核苷酸载体中。如本文所用的,术语“载体”指任一遗传元件,包括例如,质粒、粘粒、染色体、噬菌体、病毒等等,其当与适当的控制元件结合时能够复制并且可以在细胞之间转移多核苷酸序列。载体含有允许载体在所选的宿主细胞中复制的核苷酸序列。许多载体可以用于表达和/或克隆,并且包括,但不限于,pbr322、puc系列、m13系列、pgem系列、和pbluescript载体(stratagene,lajolla,caandpromega,madison,wi)。
本发明还涉及寡核苷酸探针和引物,如聚合酶链式反应(pcr)引物,其可以与本发明多核苷酸的编码或非编码序列杂交。本发明的寡核苷酸探针可以用于检测流感病毒核酸序列的方法中。本发明的寡核苷酸引物可以用于pcr方法和涉及核酸扩增的其他方法中。在优选实施方案中,本发明的探针或引物可以与本发明的多核苷酸在严格条件下杂交。本发明的探针和引物可以任选包含检测标记或者报道分子,如荧光分子、酶、放射性部分,等等。本发明的探针和引物对于使用它们的方法或测定法可以是任何合适的长度。通常,本发明的探针和引物将长为10到500个或者更多核苷酸。在本发明的范围内预期长为10到20、21到30、31到40、41到50、51到60、61到70、71到80、81到90、91到100或101个或更多核苷酸的探针和引物。在一个实施方案中,探针和引物长为9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29或30个核苷酸的任一个。本发明的探针和引物可以与所述多核苷酸序列具有完全(100%)的核苷酸序列同一性,或者序列同一性可以小于100%。例如,探针或引物和序列之间的序列同一性可以为99%、98%、97%、96%、95%、90%、85%、80%、75%、70%或者任一其他百分数序列同一性,只要该探针或引物可以在严格条件下与本发明的多核苷酸的核苷酸序列杂交。本发明的示例的探针和引物包括具有seqidno:35、seqidno:36、seqidno:37、seqidno:38、seqidno:39、seqidno:40、seqidno:41、seqidno:42、seqidno:43、seqidno:44、seqidno:45和seqidno:46的任一个中所示的核苷酸序列,或者seqidno:35-46的任一个的功能片段或者变体的那些探针和引物。
如本文所用的,术语“核酸”、“多核苷酸”和“寡核苷酸”指单链或者双链形式的脱氧核糖核苷酸、核糖核苷酸或者混合的脱氧核糖核苷酸和核糖核苷酸聚合物,并且除非另外限制,将包括天然核苷酸的已知的类似物,其可以以类似于天然存在的核苷酸的方式发挥功能。多核苷酸序列包括可以转录成rna的dna链序列和可以翻译成蛋白质的rna链。本发明的任一核酸、多核苷酸或者寡核苷酸的互补序列也预期在本发明的范围内。多核苷酸序列还包括全长序列以及衍生自全长序列的较短的序列。本发明还包括序列与本文公开的多核苷酸互补的那些多核苷酸。本发明的多核苷酸和多肽可以以纯化或者分离的形式提供。
因为遗传密码的简并性,多种不同的多核苷酸序列可以编码本发明的多肽。在lewin(1985)中描述了显示所有可能的三联体密码子(并且其中u也代表t)和每个密码子编码的氨基酸的表格。此外,本领域技术人员完全能够产生编码与本发明的多肽相同或者基本相同的多肽的备选的多核苷酸序列。这些简并变体和备选多核苷酸序列在本发明的范围内。如本文使用的,对“基本上相同”的序列的引用指编码氨基酸替代、缺失、添加或者插入的序列,其不实质上改变本发明的多核苷酸编码的多肽的功能和/或免疫原性活性。
本发明还涉及编码本发明多肽的本发明的多核苷酸的变体。变体序列包括那些序列,其中该序列的一个或多个核苷酸已经被替代、缺失和/或插入。可以替代dna的天然核苷酸的核苷酸具有碱基部分,其可以包括,但不限于,次黄苷、5-氟尿嘧啶、5-溴尿嘧啶、次黄嘌呤、1-甲基鸟嘌呤、5-甲基胞嘧啶,和三苯甲基化碱基。序列中核苷酸的糖部分还可以是经修饰的并且包括,但不限于,阿拉伯糖、木酮糖和己糖。此外,可以用乙酰基、甲基和/或硫代基团修饰核苷酸的腺嘌呤、胞嘧啶、鸟嘌呤、胸腺嘧啶和尿嘧啶碱基。使用本领域中已知的标准技术可以制备和测试含有核苷酸替代、缺失、和/或插入的序列。
本发明的范围内还预期与本发明的多肽中那些特别示例或者天然存在的氨基酸不同的氨基酸替代。例如,非天然氨基酸可以替代多肽的氨基酸,只要具有替代氨基酸的多肽基本上保留与没有替代的氨基酸的多肽相同的功能活性。非天然氨基酸的实例包括,但不限于,鸟氨酸、瓜氨酸、羟脯氨酸、高丝氨酸、苯基甘氨酸、牛磺酸、碘代酪氨酸、2,4-二氨基丁酸、α-氨基异丁酸、4-氨基丁酸、2-氨基丁酸、γ-氨基丁酸、ε-氨基己酸、6-氨基己酸、2-氨基异丁酸、3-氨基丙酸、正亮氨酸、正缬氨酸、肌氨酸、高瓜氨酸、半胱磺酸、τ-丁基甘氨酸、τ-丁基丙氨酸、苯基甘氨酸、环己基丙氨酸、β-丙氨酸、氟-氨基酸、设计者氨基酸,如β-甲基氨基酸、c-甲基氨基酸、n-甲基氨基酸、和一般的氨基酸类似物。非天然氨基酸还包括具有衍生的侧基的氨基酸。此外,蛋白质中的任一氨基酸可以为d(右旋)型或者l(左旋)型。本发明的范围内还包括本发明多肽的蛋白质序列的等位基因变体。
氨基酸可以一般以下面的类别分类:非极性的、不带电的极性的、碱性的和酸性的。保守替代(其中具有一个类别氨基酸的本发明的多肽用相同类别的另一氨基酸替代)落入本发明的范围内,只要具有替代的多肽仍然保留与不具有该替代的多肽基本上相同的功能活性。编码序列中具有一个或多个氨基酸替代的多肽的多核苷酸包括在本发明的范围内。下面的表11提供了属于每个类别的氨基酸的实例列表。在表12中定义了单字母氨基酸缩写。
使用本领域中已知的标准方法可以产生本发明的流感病毒多肽的片段和变体并且使用本领域中已知的标准技术测试功能或者免疫原性的存在。例如,为了测试本发明的神经氨酸酶多肽的片段和/或变体,可以测定酶促活性。从而,普通技术人员可以容易制备和测试本发明多肽的片段和变体,并确定该片段或变体是否相对于全长或者非变异多肽保持活性。
本发明范围内预期的多核苷酸和多肽也可以按照与本文特别示例的本发明的那些序列的更具体的同一性和/或相似性范围定义。序列同一性将通常大于60%,优选大于75%,更优选大于80%,甚至更优选大于90%,并且可以大于95%。与本文示例的序列相比,序列的同一性和/或相似性可以为49、50、51、52、53、54、55、56、57、58、59、60、61、62、63、64、65、66、67、68、69、70、71、72、73、74、75、76、77、78、79、80、81、82、83、84、85、86、87、88、89、90、91、92、93、94、95、96、97、98或99%。除非另外指出,如本文使用的,两个序列的百分比序列同一性和/或相似性可以使用karlin和altschul(1990)的,如在karlin和altschul(1993)中改进的算法确定。这种算法整合到altschuletal.(1990)的nblast和xblast程序中。可以用nblast程序,得分=100,字长=12进行blast搜索,以得到具有所希望的百分比序列同一性的序列。为了得到用于比较目的的缺口比对,可以使用如altschuletal.(1997)的gappedblast。当利用blast和gappedblast程序时,可以使用各自程序(nblast和xblast)的默认参数。见ncbi/nih网站。
本发明还预期这样的多核苷酸分子,其具有与本文示例的多核苷酸序列足够同源的序列,从而允许与该序列在标准的严格条件和标准方法(maniatisetal.,1982)下杂交。如本文使用的,杂交的“严格”条件指这样的条件,其中通常在6xsspe,5xdenhardt溶液,0.1%sds,0.1mg/ml变性dna中低于dna杂交分子的解链温度(tm)20-25℃下过夜进行。通过下面的公式描述解链温度tm(beltzetal.,1983):
tm=81.5c+16.6log[na+]+0.41(%g+c)-0.61(%甲酰胺)-600/双链体长度(以碱基对计)。
通常如下进行洗涤:
(1)在1xsspe,0.1%sds中室温下洗涤两次,每次15分钟(低严格洗涤)。
(2)在0.2xsspe,0.1%sds中tm-20℃下洗涤一次15分钟(中等严格洗涤)。
本发明还涉及本发明的流感病毒的基因编码的病毒蛋白质和肽。在一个实施方案中,病毒蛋白是成熟ha蛋白。在特定实施方案中,成熟的ha蛋白包含下面的一个或多个:82位的丝氨酸;221位的亮氨酸;327位的苏氨酸;和/或482位的苏氨酸。在示例的实施方案中,成熟的ha蛋白质具有seqidno:33或seqidno:34中所示的氨基酸序列,或者seqidno:33或seqidno:34的功能和/或免疫原性片段或变体。在另一实施方案中,病毒蛋白是na蛋白、ns蛋白、pb蛋白、pa蛋白、或者ma蛋白。本发明的病毒蛋白质和肽可以用于产生特异结合所述蛋白质或肽的抗体。本发明的病毒蛋白质和肽还可以用作疫苗组合物中的免疫原。
本发明还涉及用于诱导针对流感病毒的免疫应答的组合物和方法,所述流感病毒能够感染易感的宿主动物和引起呼吸系统疾病。本发明可以用于在易感的宿主动物中诱导针对任一亚型的流感病毒的免疫应答。例如,流感病毒可以是h1、h2、h3、h4、h5、h6、h7、h8、h9、h10、h11、h12、h13、h14、h15或h16的ha亚型,和n1、n2、n3、n4、n5、n6、n7、n8或n9的na亚型。在一个实施方案中,ha亚型是h3或者h5。在另一实施方案中,na亚型是n7或者n8。在特定实施方案中,诱导针对亚型h3n8的流感病毒的免疫应答。在一个实施方案中,宿主动物是犬科动物。犬科动物包括野生的、动物园的和驯养的犬科动物,如狼、郊狼和狐狸。犬科动物还包括狗,尤其驯养的狗,如纯种和/或杂种陪伴狗、表演狗、役用狗、放牧狗、猎狗、守卫狗、警犬、赛犬和/或实验用狗。在特定实施方案中,宿主动物是驯养的狗,如灵
如本文所用的,本发明的疫苗或者免疫原性组合物可以包含无细胞的完整病毒,包括减毒的或者失活的病毒,或者病毒的部分,包括亚病毒颗粒(包括“分离疫苗”,其中处理病毒体以除去一些或者全部病毒脂类)、病毒蛋白质(包括个体蛋白质和多种蛋白质的大分子复合体)、多肽、和肽,以及病毒感染的细胞系,或者这些任一种的组合。包含病毒感染的细胞系的疫苗或者免疫原性组合物可以包含多种细胞系,每种用不同的病毒毒株感染。
本发明的疫苗或者免疫原性组合物还包含重组的基于病毒载体的构建体,其可以包含例如编码本发明的流感病毒的ha蛋白、na蛋白、核蛋白、聚合酶碱性蛋白、聚合酶酸性蛋白,和/或基质蛋白的基因。可以用于制备重组载体/病毒构建体的任何合适的病毒载体预期用于本发明。例如,来自腺病毒、禽痘、疱疹病毒、牛痘、金丝雀痘、昆虫痘、猪痘、西尼罗病毒和本领域已知的其他病毒的病毒载体可以用于本发明的组合物和方法中。可以使用本领域中已知的标准遗传工程技术构建编码和表达组分的重组多核苷酸载体。此外,本文描述的多种疫苗组合物可以单独使用和相互组合使用。例如,动物的初次免疫可以使用重组的基于载体的构建体,其具有单个或者多个毒株组分,然后用包含失活病毒或者失活的病毒感染的细胞系的疫苗组合物二次加强。使用本发明的疫苗组合物的其他免疫方案是本领域技术人员显而易见的并且预计在本发明的范围内。
本发明还涉及重排列病毒,其包含本发明的流感病毒的至少一种基因或者基因组区段和来自本发明的不同的流感病毒或者来自不同于本发明病毒的流感病毒的病毒基因或者基因组区段的剩余部分。通过本发明的供体流感病毒的核酸与受体流感病毒的核酸的遗传重排列,然后选择包含供体病毒的核酸的重排列病毒,可以产生重排列病毒。产生和分离重排列病毒的方法是本领域中公知的(fieldsetal.,1996)。在一个实施方案中,本发明的重排列病毒包含人类、鸟类、猪或者马流感病毒的基因或者基因组区段。本发明的重排列病毒可以包括来自供体和受体流感病毒的核酸的任一组合,只要重排列病毒包含来自本发明的供体流感病毒的至少一个基因或者基因组区段。在一个实施方案中,受体流感病毒可以是马流感病毒。
病毒蛋白质的天然的、重组的或者合成的多肽,和其肽片段也可以用作根据本发明方法的疫苗组合物。在一个实施方案中,来自多种毒株的病毒多肽可以组合在疫苗组合物中并且用于接种宿主动物。例如,基于来自至少两种不同毒株的本发明的流感病毒的病毒ha蛋白质的多肽可以组合在疫苗中。该多肽可以与一种毒株同源或者可以包含“杂合”或“嵌合”多肽,其氨基酸序列来自结合或者连接来自至少两种不同毒株的多肽。制备病毒多肽的步骤是本领域公知的。例如,使用固相合成方法(merrifield,1963)可以合成病毒多肽和肽。使用重组dna技术也可以产生病毒多肽和肽,其中编码病毒蛋白质或者肽的多核苷酸分子在宿主细胞,如细菌、酵母或者哺乳动物细胞系中表达,并且使用本领域的标准技术纯化表达的蛋白质。
本发明的疫苗组合物还包括裸核酸组合物。在一个实施方案中,核酸可以包含编码本发明的流感病毒的ha和/或na蛋白质的核苷酸序列。核酸接种的方法是本领域中已知的并且描述于例如美国专利号6,063,385和6,472,375。核酸可以为质粒或者基因表达盒的形式。在一个实施方案中,将核酸包裹在脂质体中提供,将所述脂质体施用于动物。
可以为根据本发明使用的疫苗组合物和免疫原,如多肽和核酸提供可药用载体或者稀释剂。可以根据制备药学上有用的组合物的已知方法配制用于本发明的化合物和组合物。在本领域技术人员公知和容易得到的许多来源中详细描述了制剂。例如,e.w.martin,eastonpennsylvania,mackpublishingcompany,19thed.,1995的remington’spharmaceuticalscience描述了可以用于本发明的制剂。通常,将配制本发明的组合物使得有效量的免疫原与合适的载体组合以便促进组合物的有效施用。用于本发明方法中的组合物还可以为多种形式。这些包括例如,固体、半固体和液体剂型,如片剂、丸剂、粉剂、液体溶液剂或混悬剂、栓剂、注射液和灌注液,和喷雾剂。优选的形式取决于预期的施用方式和治疗应用。组合物还优选包括本领域技术人员已知的常规的可药用载体和稀释剂。用于本发明肽模拟物的载体或稀释剂的实例包括,但不限于,水、盐水、油,包括矿物油、乙醇、二甲基亚砜、明胶、环糊精、硬脂酸镁、葡萄糖、纤维素、糖、碳酸钙、甘油、氧化铝、淀粉和等同的载体和稀释剂,或者这些任一种的混合物。本发明免疫原的制剂还可以包含悬浮剂、保护剂、润滑剂、缓冲剂、防腐剂和稳定剂。为了提供施用此类剂量用于所希望的治疗性治疗,本发明的药物组合物将有利地包含基于包括载体或稀释剂的总组合物的重量按重量计约0.1%到45%,特别1到15%的一种或多种免疫原。
通过本领域公知的方法可以制备本发明的疫苗和免疫原性组合物。例如,通常将疫苗或者免疫原制备为注射剂,例如,液体溶液剂或者混悬剂。以与剂量制剂相容的方式和在受体中治疗有效和免疫原性的量施用疫苗或者免疫原。本领域技术人员可以容易地确定具体疫苗或者免疫原制剂的最佳剂量和施用模式。
还可以以多抗原肽(map)构建体的形式提供本发明的肽和/或多肽。已经在tam(1988)描述了map构建体的制备。map构建体利用赖氨酸残基的核心基质,其上合成多个拷贝的免疫原(posnettetal.,1988)。可以根据本发明的方法制备并在疫苗组合物中施用多种map构建体,每种含有相同或者不同的免疫原。在一个实施方案中,为map构建体提供一种或多种佐剂和/或与一种或多种佐剂一起施用。还产生了本发明的流感多肽并且作为包含一种或多种多肽的大分子蛋白质结构施用。公布的美国专利申请us2005/0009008描述了产生作为流感病毒疫苗的病毒样颗粒的方法。
根据本发明的方法,将本文描述的疫苗和免疫原性组合物施用于易感宿主,通常犬科动物,并且更通常为驯养的狗,以诱导保护性免疫以抵抗病毒对宿主随后的攻击或者感染的有效量和方式施用。在一个实施方案中,宿主动物是犬科动物。犬科动物包括野生的、动物园的和驯养的犬科动物,如狼、郊狼和狐狸。犬科动物还包括狗,尤其驯养的狗,如纯种和/或杂种陪伴狗、表演狗、役用狗、放牧狗、猎狗、守卫狗、警犬、赛犬和/或实验用狗。在特定实施方案中,宿主动物是驯养的狗,如灵
使用本领域中已知的方法,可以将疫苗制剂中的病毒和病毒感染的细胞失活或者减毒。例如,通过暴露于低聚甲醛、福尔马林、苯酚、紫外线、高温等等可以失活或者减毒完整病毒和受感染的细胞。疫苗剂量中无细胞的完整病毒的量将通常为约0.1mg到约5mg,更通常约0.2mg到约2mg。包含病毒感染的细胞系的疫苗制剂的剂量将通常含有每剂约106到约108个细胞,更通常每剂约5x106到约7.5x107个细胞。用于动物的剂量中蛋白质或肽免疫原的量可以从约0.1μg到10000μg,或约1μg到5000μg,或约10μg到1000μg,或约25μg到750μg,或约50μg到500μg,或100μg到250μg,取决于接受剂量的动物的大小、年龄等等。
本发明的免疫原性或者疫苗组合物,如病毒或者病毒感染的细胞或者病毒蛋白质或肽可以与佐剂组合,通常刚好在施用前组合。设想用于疫苗制剂的佐剂包括苏氨酰基胞壁酰二肽(mdp)(byarsetal.,1987)、皂苷、cornebacteriumparvum、弗氏完全佐剂和弗氏不完全佐剂、铝,或者这些任一种的混合物。适于用于本发明的方法和疫苗的多种其他佐剂,如明矾,是本领域中公知的,并且设想用于本发明。
本发明还涉及特异结合本发明的蛋白质或者肽的抗体。本发明的抗体包括单克隆和多克隆抗体组合物。优选地,本发明的抗体是单克隆抗体。在本发明中设想完整抗体和其抗原结合片段。从而,例如,合适的抗原结合片段包括fab2、fab和fv抗体片段。本发明的抗体可以用可检测部分,如荧光分子标记(例如,萤光素或者酶)。
本发明还涉及用于检测和鉴定本发明的流感病毒和诊断本发明的流感病毒对动物的感染的方法和组合物。本发明的方法包括检测来自动物的生物样品中犬科动物流感的存在。样品中犬科动物流感的检测可用于诊断动物中的犬科动物流感。该信息又可以提供基于区分随时间存在的犬科动物流感的水平来预后动物的能力,并且可以帮助选择动物的治疗剂和治疗,和帮助监测疗法。该方法还提供了确立在测试的动物中不存在犬科动物流感的能力。
检测动物中犬科动物流感的能力允许评估不同的地理位置中犬科动物流感的爆发。该信息还允许早期检测从而可以隔离受感染的动物,以限制疾病的传播,和允许早期干预治疗选择。此外,得到该信息可以为准备治疗许多患病动物的医学人员提供指导,包括装备药材供应,和如果可以得到,疫苗。
在一个实施方案中,本发明的方法涉及从受试动物,如犬科动物收集生物样品。生物样品可以是任一种生物样品,包括细胞、组织、毛发、全血、血清、血浆、乳头抽吸物、肺灌洗液、脑脊液、唾液、汗液和泪液。
动物受试样品可以来自怀疑具有犬科动物流感病毒的动物,无论该动物是否显示出疾病症状。还可以提供对照样品或者从已知没有犬科动物流感的动物收集。可以提供额外的对照例如,以减少假阳性和假阴性结果,和证实测定中的试剂主动检测犬科动物甲型流感病毒。
除了检测生物样品中犬科动物流感的存在或不存在,本发明中使用的检测方法可以检测犬科动物流感病毒中的突变,如核酸序列的改变,其可以由环境、药物治疗、遗传操作或者突变、损伤、食物的改变、衰老或者动物的任何其他的特征引起。突变还可以导致犬科动物甲型流感变得抵抗以前有效的药物,或者使得病毒感染和在不同物种的动物或者人类中繁殖。例如,已经表明鸟类甲型流感病毒感染其他动物和人。
在用于检测动物中流感病毒的一个实施方案中,通过收集高质量的样品、它们快速运输到检测设施、和在实验室检验前合适的保存方便了诊断。在含有受感染的细胞和分泌物的样品中最佳地检测到病毒。在一个实施方案中,在临床症状发作后前3天内采集用于直接检测病毒抗原和/或核酸和/或病毒分离的样品。多种类型的样本适于诊断上呼吸道的病毒感染,包括,但不限于,鼻拭子、鼻咽拭子、鼻咽抽吸物、鼻洗液和喉咙拭子。除了拭子外,还可以采集组织或者血清的样品,并且还可以进行侵入性步骤。
在一个实施方案中,收集呼吸系统样品并以1-5ml病毒运送培养基运输。满足多种病毒的回收的多种培养基可通过商业途径获得。向运送培养基中加入临床样品。还可以用病毒运送培养基运送鼻或者鼻咽拭子。运送培养基的一个实例是10克小牛肉浸汁和2克牛白蛋白级分v,加入到无菌蒸馏水至400m。也可以加入抗生素,如0.8ml硫酸庆大霉素溶液(50mg/ml)和3.2ml两性霉素b(250μg/ml)。优选通过过滤消毒培养基。鼻洗液,如无菌盐水(0.85%nacl)也可以用于收集呼吸系统病毒的样品。
在一个实施方案中,在临床症状发生后不久,优选不迟于7天内,从急性期动物的1-5ml量的全血收集血清。还例如在症状发生后约14天收集恢复期血清样品。在中和试验中,血清样品可以用于检测抗呼吸系统病毒的抗体。
在一个实例中,可以在一定期限内(例如,每天一次,每周一次,每月一次,每半年一次或者每年一次)从个体动物收集样品。在一定时期内从个体动物得到多个样品可以用于验证来自更早检测的结果,和/或鉴定对特定治疗,例如,对所选的治疗药物的应答或者抗性。
本发明的方法可以用于检测来自动物的受试样品中一种或多种病理物质的存在,和每种病理物质的水平。可以使用用于检测病理物质的任何方法,包括但不限于,抗体测定法,包括酶联免疫吸附测定(elisa)、间接荧光抗体(ifa)检测、血细胞凝集,和血细胞凝集抑制(hi)测定法,和蛋白质印迹。也可以使用已知的细胞培养方法。使用细胞培养物的免疫荧光或者细胞培养基(上清液)的hi测定法,可以进一步鉴定阳性培养物。
此外,可以使用检测核酸(dna或者rna)或者蛋白质的方法。此类方法包括,但不限于,聚合酶链式反应(pcr)和逆转录酶(rt)pcr测试和实时测试,和定量核酸酶保护测定法。可利用通过商业途径可获得的测试试剂盒用于进行这些测定法。例如,qiagen(valencia,ca)出售一步rt-pcr试剂盒,和病毒rna提取试剂盒。
在一个实施方案中,该方法利用对本发明的病毒或病毒蛋白质特异的抗体。在特定实施方案中,利用对本发明病毒的ha蛋白质特异的抗体。在一个实施方案中,使用对本发明病毒的np蛋白质特异的抗体。从动物得到合适的样品,如来自鼻或者鼻咽区域的样品,并从中分离病毒或者病毒蛋白质。然后对病毒组分筛选对蛋白质,如本发明病毒的ha或者np特异的抗体的结合。在另一实施方案中,从动物得到血清样品(或者其他含有抗体的样品)并对血清筛选结合本发明病毒的蛋白质的抗体的存在。例如,可以进行elisa测定,其中平板壁具有结合到壁的ha和/或np蛋白质,或者其肽片段。然后将平板壁与来自受试动物的血清或者抗体接触。动物中特异结合ha和/或np蛋白质的抗体的存在表明该受试动物受到或者已经受到本发明的流感病毒的感染。
在一个实施方案中,通过测定生物样品中抗病理物质的抗体的存在或不存在,检测病理物质的存在。在动物受感染后可以在血液检验中检测到抗体之前,需要一定的时间(例如,数月)。抗体一旦形成,通常持续许多年,甚至在成功地治疗该疾病之后。发现针对犬科动物甲型流感病毒的抗体不能指出感染是最近的还是在过去的某个时间。
还可以用液体进行抗体测试。抗体测定法包括酶联免疫吸附测定(elisa)、间接荧光抗体(ifa)测定法,和蛋白质印迹。优选地,使用多种测定法,如elisa或者ifa,接着通过蛋白质印迹进行抗体测试。在两步方法中,使用elisa或者ifa测定法,接着通过蛋白质印迹进行抗体测定法。认为elisa是比ifa更可靠和更准确的测定法,但是如果不能利用eilsa,那么可以使用ifa。蛋白质印迹测试(其是更特异的测试)也可以在所有动物中进行,尤其在那些在elisa或者ifa测定中检测为阳性或者临界阳性(含糊的)的动物中进行。
可以用于检测流感病毒的其他基于抗体的测试包括血细胞凝集抑制测定法。如所述的使用鸡或者火鸡红细胞(burlesonetal.,1992)和kendaletal.,1982),可以检测来自动物的生物样品中的血细胞凝集活性。在一个实施方案中,将本发明的流感或者ha蛋白或者肽与含有血清或者抗体的测试样品接触。然后加入来自动物如鸟的红细胞(rbc)。如果存在抗ha的抗体,那么rbc将不凝集。如果不存在抗ha的抗体,那么在ha存在下,rbc将凝集。对标准血细胞凝集抑制测定法的变更和修改是本领域中已知的并且设想在本发明的范围内。
通过从样品如鼻或者鼻咽拭子分离病毒,可以确定动物的感染。使用标准方法,包括细胞培养和鸡胚接种,可以进行病毒分离。
在进一步的实施方案中,可以用基于核酸的测定法检测本发明的病毒。在一个实施方案中,从动物得到核酸样品并将该核酸进行pcr,如果该核酸含有对本发明的流感病毒特异的序列,那么使用的引物将产生扩增产物。在特定实施方案中,在测定中将rt-pcr用于本发明病毒。在示例的实施方案中,用实时rt-pcr测定本发明的流感病毒。pcr、rt-pcr和实时pcr方法是本领域中已知的并且已经在美国专利号4,683,202;4,683,195;4,800,159;4,965,188;5,994,056;6,814,934;和saikietal.(1985);sambrooketal.(1989);leeetal.(1993);和livaketal.(1995)中。在一个实施方案中,pcr测定法使用对流感基质(ma)基因和/或ha基因特异的寡核苷酸。还可以对扩增产物测序以确定该产物是否具有本发明的流感病毒的序列。其他基于核酸的测定法可以用于检测和诊断本发明病毒的病毒感染并且设想此类测定法在本发明的范围内。在一个实施方案中,将含有核酸的样品进行基于pcr的扩增,使用正向和反向引物,其中所述引物对病毒多核苷酸或者基因序列特异。如果样品中的核酸是rna,那么可以进行rt-pcr。对于实时pcr,将可检测的探针与引物一起使用。
对许多循环流感病毒的血凝素(ha)基因特异的引物组是已知,并且正在被不断开发出来。流感病毒基因组是单链rna,并且必须使用逆转录酶(rt)聚合酶进行dna拷贝(cdna)。例如,使用rt-pcr对rna基因组的扩增需要一对寡核苷酸引物,其通常基于甲型流感病毒亚型的已知的ha序列和神经氨酸酶(nm)-1设计。可以选择引物使得它们将特异扩增仅一种病毒亚型的rna。使用亚型特异的引物产生的dna可以通过分子遗传学技术如测序进一步分析。试验优选用阳性对照进行,或者产物通过测序并与已知序列比较来验证。不存在目标pcr产物(即,“阴性”结果)不能排除病毒的存在。然后可以在几小时内从临床拭子或者感染的细胞培养物得到结果。甲型流感病毒的pcr和rt-pcr试验由fouchieretal.,2000和maertzdorfetal.,2004描述。
本发明还涉及筛选对本发明的病毒具有抗病毒活性的化合物或药物的方法。在一个实施方案中,将本发明的病毒感染的细胞与受试化合物或者药物接触。然后测定接触后病毒的量或者病毒活性。可以选择显示出抗病毒活性的那些化合物或者药物用于进一步评估。
本发明还涉及用本发明的流感病毒感染的分离的细胞。在一个实施方案中,所述细胞是犬科动物细胞,如犬科动物肾上皮细胞。
本发明还涉及用编码本发明多肽的本发明多核苷酸转化的细胞。优选地,在本发明的表达构建体中提供所述多核苷酸序列。更优选地,所述表达构建体提供了在细胞中过表达有效连接的本发明的多核苷酸。在一个实施方案中,用多核苷酸序列转化细胞,所述多核苷酸序列包含编码seqidno:2、4、6、8、10、12、14、16、18、20、22、24、26、28、30、32、33、34、48、50、52、54、56、58、60、62、64、66、68、70、72、74、76或78的任一个中显示的氨基酸序列,或者其功能片段或者变体的序列。在特定实施方案中,用编码seqidno:2、4、6、8、10、12、14、16、18、20、22、24、26、28、30、32、33、34、48、50、52、54、56、58、60、62、64、66、68、70、72、74、76或78中所示的氨基酸序列的多核苷酸转化的细胞分别包含seqidno:1、3、5、7、9、11、13、15、17、19、21、23、25、27、29、31、47、49、51、53、55、57、59、61、63、65、67、69、71、73、75或77中所示的核苷酸序列,或者编码seqidno:2、4、6、8、10、12、14、16、18、20、22、24、26、28、30、32、33、34、48、50、52、54、56、58、60、62、64、66、68、70、72、74、76或78的任一个的功能片段或者变体的序列。从而,本发明涉及用包含seqidno:1、3、5、7、9、11、13、15、17、19、21、23、25、27、29、31、47、49、51、53、55、57、59、61、63、65、67、69、71、73、75或77的任一个中所示的核苷酸序列或者seqidno:1、3、5、7、9、11、13、15、17、19、21、23、25、27、29、31、47、49、51、53、55、57、59、61、63、65、67、69、71、73、75或77的任一个的片段或者变体,包括简并变体的多核苷酸序列转化的细胞。
所转化的细胞可以是真核细胞,例如,植物细胞,包括原生质体,或者转化的细胞可以是原核细胞,例如,细菌细胞,如大肠杆菌或者枯草芽孢杆菌。动物细胞包括人细胞,哺乳动物细胞,部分犬科动物细胞、鸟类细胞和昆虫细胞。植物细胞包括,但不限于,双子叶植物细胞、单子叶植物细胞和针叶树细胞。
本发明还涉及表达和产生本发明的病毒蛋白或者多肽的转基因植物。本发明设想用本发明的多核苷酸转化或者经育种而含有本发明的多核苷酸的植物、植物组织和植物细胞。优选地,在植物、植物组织或者植物细胞中过表达本发明的多核苷酸。植物可以用于产生本发明的流感疫苗组合物并且可以通过植物的消费施用疫苗(见,例如,美国专利号5,484,719和6,136,320)。
本发明还涉及用于检测病毒或者诊断本发明的病毒感染的试剂盒。在一个实施方案中,试剂盒包含本发明的抗体,其特异结合本发明的流感病毒,或者其抗原性部分。在另一实施方案中,试剂盒包含本发明的一种或多种多肽或者肽。在特定实施方案中,所述多肽具有seqidno.2、4、6、8、10、12、14、16、18、20、22、24、26、28、30、32、33、34、48、50、52、54、56、58、60、62、64、66、68、70、72、74、76或78任一个中所示的氨基酸序列,或者其功能和/或免疫原性片段或变体。在另一实施方案中,试剂盒包含一种或多种本发明的多核苷酸或者寡核苷酸。在特定实施方案中,所述多核苷酸具有seqidno.1、3、5、7、9、11、13、15、17、19、21、23、25、27、29、31、47、49、51、53、55、57、59、61、63、65、67、69、71、73、75或77任一个中所示的核苷酸序列,或者其片段或者变体。试剂盒可以任选包含一种或多种对照抗体、对照多肽或者肽,和/或对照多核苷酸或者寡核苷酸。试剂盒的抗体、多肽、肽、多核苷酸和/或寡核苷酸可以在合适的容器或者包装中提供。
本申请还涉及杂种狗作为流感病毒感染和发病机理模型的用途。在一个实施方案中,对杂种狗接种本发明的流感病毒,如犬科动物流感病毒。任选地,接种后可以对狗施用治疗剂。在用病毒接种之前,还可以对狗施用组合物用于产生针对流感病毒的免疫应答。可以在接种之前和/或之后得到组织、血液、血清和其他生物样品并使用本领域中已知的方法检查病毒的存在和组织的发病机理,所述方法包括,但不限于,pcr、rt-pcr、核酸测序,和免疫组织化学。
本文公开的任一实施方案的任一元素可以与本文的任何其他元素或者实施方案组合,并且特别设想此类组合在本发明的范围内。
本文提及或者引用的所有专利、专利申请、临时申请和出版物都完整(包括所有图和表)引入本文作为参考,直到它们与本说明书的明确教导不一致的程度。
实施例1-6的材料和方法
从灵
从在赛跑狗舍中经历呼吸系统疾病爆发的临床上患病的或者正常的灵
灵
由佛罗里达大学兽医学院(universityoffloridacollegeofveterinarymedicine(ufcvm))的解剖病理学处(anatomicpathologyservice)对2004年1月在佛罗里达赛场的爆发中死亡的8只灵
犬科动物呼吸系统病原体的血清学试验
将配对的急性和恢复期血清样品递交给康耐尔大学兽医学院(cornelluniversitycollegeofveterinarymedicine)的动物健康诊断实验室(animalhealthdiagnosticlaboratory(ahdl)),对犬瘟热病毒、2型腺病毒和副流感病毒进行血清中和测定。抗体效价表达为抑制细胞培养物的病毒感染的血清的最终稀释度。血清转变表明病毒感染,将血清转变定义为急性和恢复期样品之间抗体效价升高≥4倍。没有检测到对这些病毒病原体的血清转变。
犬科动物细菌呼吸系统病原体的微生物试验
将配对的鼻拭子和死后组织递交给ufcvm的诊断临床微生物学/寄生虫学/血清学处(diagnosticclinicalmicrobiology/parasitology/serologyservice)用于细菌分离和鉴定。在非选择培养基以及选择博德特氏菌(bordetella)种(regan-lowe;remel)和支原体(mycoplasma)种(remel)的培养基上培养样品。在没有报告生长前,保持所有培养物21天。还将一些灵
从死后组织分离病毒
将冷冻的组织解冻并在10倍体积的补充0.5%牛血清白蛋白(bsa)和抗生素的极限必需培养基(mem)中匀浆。通过离心除去固体碎片并将上清液接种到培养的细胞或者10天龄的含胚的鸡蛋中。将来自死亡灵
rt-pcr、核苷酸测序和系统进化分析
使用rneasy试剂盒(qiagen,valencia,ca)根据生产商的使用说明,从组织培养物上清液或者尿囊液提取总rna。使用一步rt-pcr试剂盒(qiagen,valencia,ca)根据生产商的使用说明将总rna(10ng)逆转录成cdna。如以前描述的(klimovetal.,1992a),使用通用的基因特异性引物组进行cdna中8种流感病毒基因的编码区的pcr扩增。所得dna扩增子用作appliedbiosystems3100自动化dna测序仪上的自动化测序的模板,使用循环测序染料终止化学(abi)。用gcg
狗的实验接种
使用四只6个月龄的特定无病原体的小猎兔犬[2只雄性和2只雌性(libertyresearch)]。体检和基线血试验,包括全血细胞计数/微分、血清化学小组和尿分析确定动物是健康的。将它们养在试验动物照料评估和认证协会(associationforassessmentandaccreditationoflaboratoryanimalcare)认证的bsl2-增强型设施中。每天两次持续7天记录基线直肠温度。通过异丙酚(
病毒从实验接种的狗的脱落
通过离心澄清拭子运送培养基制备的肺匀浆物和拭子提取物的连续稀释液用补充0.5%bsa和抗生素的mem建立。如所述的(burlesonetal.,1992)使用单层mdck细胞在6孔组织培养板中进行噬菌斑测定。用含有0.8%琼脂糖和1.5ug/mltpck-胰蛋白酶的补充的mem覆盖接种的细胞单层。在固定和用结晶紫染色前,在含有5%co2的增湿的空气中37℃下培养细胞72小时。病毒浓度表达为每克组织或者每个拭子的噬斑形成单位(pfu)。
免疫组织化学
在bond-ritetm载玻片(richard-allanscientific,kalamazoo,mi)上封固来自灵
血细胞凝集抑制(hi)测定法
在37℃下用受体破坏酶(rde,denka)(1份血清:3份rde)温育血清样品16小时,然后在56℃热失活60分钟。在37℃下在mdck细胞中培养influenzaa/canine/fl/04(h3n8)病毒36-48小时。收获病毒培养上清液,通过离心澄清,并在-80℃保存。如以前描述的进行hi测定法(kendaletal.,1982)。简言之,将25μl中的4血凝单位病毒加入微量滴定孔中等体积的连续稀释的血清,并在室温温育30分钟。加入等体积的0.5%v/v火鸡红细胞并在30分钟后通过视觉评估血细胞凝集效价。将终点hi效价定义为完全抑制血细胞凝集的血清的最后稀释度。将血清转变定义为配对的急性和恢复期样品之间的hi效价≥4倍增加。将单个样品的血清阳性定义为≥1:32的hi抗体效价。
微量中和(mn)测定
通过如以前描述的mn测定法(roweetal.,1999)检测对a/canine/fl/04(h3n8)的中和血清抗体应答,只是在测定前对犬血清进行如上述的rde处理。将终点效价定义为得到病毒的100tcid5050%中和的血清的最高稀释度。将血清转变定义为配对的急性和恢复期样品之间mn效价≥4-倍增加。将单个样品的血清阳性定义为mn效价≥1:80。
下面是阐明实施本发明方法的实例。不应该将这些实施例理解为限制。除非另外指出,所有百分数都是按重量计并且所有溶剂混合物比例都是按体积计。
实施例1
在2004年1月,在florida赛场的2个狗舍中喂养的22只竞赛灵
两种临床综合征是明显的:较轻微的病,其特征是最初的发热和然后咳嗽10-14天(14只狗),随后恢复,或者过急性死亡,伴随着呼吸道中的出血(8只狗,死亡率为36%)。对8个死亡病例的6例进行了尸体剖检。所有狗都在肺、纵隔和胸膜腔中具有广泛的出血。对呼吸道的组织学检查揭示除了肺部出血外,所有狗都具有气管炎、支气管炎、细支气管炎和化脓性支气管肺炎(图3)。这些组织中上皮层和气道腔中浸润嗜中性粒细胞和巨噬细胞。将从这些狗制备的肺匀浆物接种到多种猴、人、牛和犬细胞系用于病毒培养。来自一条狗的肺匀浆物在胰蛋白酶存在下在培养的madin-darby犬肾上皮细胞(mdck)中引起细胞病变效应,并且细胞培养上清液凝集了鸡红细胞。通过商业elisa检测甲型和乙型流感病毒的核蛋白,和通过使用对甲型流感病毒的基质基因特异的引物进行pcr分析,提供甲型流感病毒的初步证据。此外,通过针对马甲型流感h3亚型的参照抗血清抑制了血细胞凝集活性,但是通过对人甲型流感亚型h1-h11和h13特异的抗血清没有抑制血细胞凝集活性(表3)。为了表征病毒的分子性质,我们测定了病毒基因组的8个rna区段的核苷酸序列。与已知的流感病毒基因的序列比较和系统进化分析表明犬分离群的8种基因与来自同时代的马甲型流感(h3n8)病毒最相似,它们与所述病毒的基因共有≥96-97%的序列同一性(图1a,表4)。相比,来自鸟类、猪和人甲型流感分离株的代表性基因与犬分离群具有≤94%同一性(表4)。这些数据将犬分离群a/canine/florida/43/04(canine/fl/04)鉴定为与马流感病毒的同时代谱系密切相关的甲型流感h3n8病毒。因为犬分离群的所有基因都是马流感病毒来源的,所以我们推断马流感病毒的整个基因组已经转移到狗。
实施例2
为了研究canine/fl/04在灵
实施例3
为了确定canine/fl/04-样病毒参与呼吸系统疾病爆发的病因,我们通过血细胞凝集抑制(hi)和微量中和法(mn)分析了来自11只病狗和16只无症状接触狗的急性和恢复期血清。在两种测定法中,在11只中的8只(73%)病狗中发生了血清转变,其定义为对canine/fl/04的抗体效价从急性到恢复期升高≥4-倍(表1)。在hi测定中,16只中的6只(38%)无症状接触狗中发生血清转变,而在mn测定法中,16只中的8只(50%)血清转变(表1)。血清转变数据表明canine/fl/04-样病毒对狗的感染,其与多数动物中呼吸系统疾病的发作在时间上吻合。
在与病狗一起喂养的额外的46只无症状狗的爆发后3个月,收集单个血清样品。其中,在两种测定法中43只(93%)为血清阳性。对于所测试的73只狗的总群体中,93%的在两种测定中为血清阳性,包括82%(9/11)只病狗和95%(59/62)健康接触狗。没有呼吸系统疾病史的狗中的高血清阳性率表明犬科动物流感病毒的多数感染是亚临床的并且提示病毒在狗中的有效传播。亚临床感染是否促进病毒的传播还是未知的。
实施例4
为了更好地理解canine/fl/04病毒感染狗的能力,用106.6半数组织培养感染量(tcid50)通过气管内和鼻内途径接种四只6月龄purpose-品种的小猎兔犬的每一只。所有狗在接种后前2天(p.i.)都发生发热(直肠温度≥39℃),但是在14天的观察期内没有一只显示出呼吸症状,如咳嗽或者鼻涕。通过用鼻或者口咽拭子定量病毒检查病毒脱落。4只狗的仅仅两只脱落可检测量的病毒。一只狗在接种后1和2天脱落病毒(每个拭子1.0-2.5log10pfu),而另一只狗在接种后连续四天脱落病毒(每个拭子1.4-4.5log10pfu)。在5p.i.对两只狗的尸体剖检揭示了类似于在灵
实施例5
为了研究在2004年1月爆发前,canine/fl/04-样流感病毒是否已经在佛罗里达的灵
实施例6
从2004年6月到8月,在佛罗里达、德克萨斯、阿拉巴马、阿肯色、西佛吉尼亚和堪萨斯州的14个赛场的几千只竞赛灵
一些赛场的官员估计他们至少80%的狗群体患有临床疾病。多数狗具有与2004年1月爆发中的狗类似的发热(≥39oc)和咳嗽的临床病征,但是许多狗也具有粘液脓性鼻涕。报导了多例死亡,但是不能确定准确的死亡率。
我们收集了位于4佛罗里达赛场的94只狗的配对的急性和恢复期血清:56%的这些狗对canine/fl/04的抗体效价升高≥4倍,100%为血清阳性的(表6)。来自西佛吉尼亚和堪萨斯州的29只狗的恢复期血清也具有抗canine/fl/04的抗体。我们从德克萨斯赛场的死于出血性支气管肺炎的灵
canine/fl/03、canine/fl/04和canine/tx/04的ha基因的系统进化分析表明它们组成单源群,具有有力的自引支持度,其与2002和2003年分离的马病毒的同时代h3基因明显不同(图1b)。其他7种基因组区段的系统发生分析和逐对核苷酸序列比较提示犬基因隔离为与马病毒谱系最密切相关的不同的亚谱系(数据未显示,和表4)。在ha中存在4个标记氨基酸改变也支持犬流感基因聚类为与马流感分离的单源群(表2)。与来自2003和2004年的血清学结果一起,这些数据与如下相一致:从马到狗的单个病毒传播事件和随后该病毒在灵
病毒ha是流感病毒的宿主物种特异性的关键决定子(suzukietal.,2000)。为了鉴定ha内可能与对犬科动物宿主的适应有关的残基,我们比较了犬ha的推导的氨基酸序列与同时代马病毒的那些氨基酸序列。在马和犬成熟ha共有氨基酸序列中有四个氨基酸不同:n83s、w222l、i328t和n483t(见表2)。犬病毒当与共有的马序列比较时具有氨基酸缺失。因此,ha马序列中的氨基酸位置7是ha犬序列中的位置6,ha马序列中的氨基酸位置29是ha犬序列中的位置28,ha马序列中的氨基酸位置82是ha犬序列中的位置82,等等。从而,四个替代的氨基酸在seqidno:33和seqidno:34中所示氨基酸序列的位置82、221、327和482。在共有序列位置83上丝氨酸对天冬酰胺的替代是未知功能重要性的改变,因为在来自其他物种的h3分子中发现多种极性残基。在接近h3ha的切割位点的共有序列位置328上的严格保守的异亮氨酸已经被苏氨酸替代。发病机理中宿主蛋白酶对ha切割的重要作用提示该改变值得进一步研究。在共有序列位置222上亮氨酸对色氨酸的替代是相当值得注意的,因为它代表与唾液酸结合口袋相邻的非保守改变,其可以调节受体功能(weisetal.,1988)。有趣的是,在222位的亮氨酸不是犬h3ha特有的,因为它通常被发现于h4、h8、h9和h12ha亚型中(nobusawaetal.,1991;kovacovaetal.,2002)。亮氨酸替代与对哺乳动物宿主的病毒特异性可能更相容,因为已经报导了亚型h4病毒对猪的感染(karasinetal.,2000)和亚型h9病毒对人和猪的感染(peirisetal.,1999)。在共有序列483位上天冬酰胺对苏氨酸的替代导致在ha2亚基中糖基化位点的丧失,该位点在所有ha亚型中保守(wagneretal.,2002)。尽管ha中这些氨基酸改变对于马病毒对狗的适应性的重要性还有待确定,但是以前已经观察到与物种间转移有关的类似的氨基酸改变(vinesetal.,1998;matrosovichetal.,2000)。在表19到25中显示了本发明的其他流感病毒蛋白质和马共有序列之间的氨基酸差异。
最初感染竞赛灵
全部哺乳动物流感病毒向不相关的哺乳动物物种的种间转移是罕见的事件。以前的研究已经提供了狗与人甲型流感(h3n2)病毒的暂时感染的有限的血清学或者病毒学证据,但不是血清学和病毒学证据两者(nikitinetal.,1972,kilbourne,etal.,1975;changetal.,1976;houseretal.,1980)。然而,没有犬科动物宿主中持续传播的证据。尽管充分记载了猪流感病毒从猪向人的直接转移(dacsoetal.,1984;kimuraetal.,1998;patriarcaetal.,1984;topetal.,1977),但是没有猪病毒在人宿主中适应的证据。在该报导中,我们提供了完整马甲型流感(h3n8)病毒向另一种哺乳动物物种狗的种间传播。犬病毒ha中独特的氨基酸替代,以及美国多个州中狗感染的血清学证据,提示该病毒适应了犬科动物宿主。因为狗是人类的主要陪伴动物,所以这些发现具有公共健康的牵连;狗可能提供新的甲型流感病毒向人类传播的新的来源。
a具有疾病的临床病征的狗的数目。
b与临床上患病狗接触喂养的无症状狗的数目。
c使用a/canine/florida/43/04病毒的血细胞凝集抑制(hi)测定法。
d使用a/canine/florida/43/04病毒的微量中和(mn)测定法。
e具有配对的急性和恢复期血清中抗体效价增加至少4倍的狗的百分比。
f在恢复期血清中具有阳性抗体效价(hi效价≥32:mn效价≥80)的狗的百分比。
g恢复期血清的几何平均抗体效价。
*成熟h3ha中的氨基酸残基(单字母代码)和位置。氨基酸代码是:a=丙氨酸,d=天冬氨酸,g=甘氨酸,i=异亮氨酸,k=赖氨酸,l=亮氨酸,m=甲硫氨酸,n=天冬酰胺,r=精氨酸,s=丝氨酸,t=苏氨酸,v=缬氨酸,w=色氨酸。
a对来自#43狗的病毒分离群的血细胞凝集抑制滴定度。
b在白鼬中产生多克隆抗血清,而在绵羊或山羊中产生所有其他抗血清。
aa/canine/florida/43/04(h3n8)基因与来自所述物种的流感病毒分离群的多数同源基因的百分比核苷酸和氨基酸(括号内)序列同一性,接着是它们的genbank序列数据库检索号。
b不可应用:在人或者猪病毒中从没有报道n8神经氨酸酶。
a从佛罗里达竞赛灵
b血清阳性狗的微量中和测定抗体效价,包括6只2003年血清阳性狗。
a使用a/canine/florida/43/04(h3n8)通过hi测试的临床上患病狗的数目。
b在急性和恢复期血清之间抗体效价升高≥4倍的狗的百分比。
c在恢复期血清中具有阳性抗体效价(hi效价>16)的狗的百分比。
d恢复期血清的几何平均抗体效价。
实施例7–11的材料和方法
犬组织
由佛罗里达大学兽医学院的解剖病理学处对6只杂种狗和一只宠物yorkshireterrier狗进行尸体剖检,所述杂种狗在2005年4月/5月流感爆发期间在佛罗里达东北部的收容所死亡,所述yorkshireterrier狗在2005年5月流感病毒爆发期间在佛罗里达东南部的兽医诊所中死亡。将组织用10%中性缓冲福尔马林固定,包埋在石蜡中,并用苏木精和伊红染色5-μm的切片用于组织病理学诊断。在病毒学分析之前,未固定的组织在-80℃保存。
从犬组织样品提取rna
将来自7只狗的每一只的冷冻的肺组织解冻并在补充0.5%牛血清白蛋白(bsa)(kendall,lifelinemedicalinc.,danbury,ct)和抗生素(庆大霉素和环丙沙星)的极限必需培养基(mem)中用一次性组织研磨机匀浆。使用商业试剂盒(
实时rt-pcr
使用含有rox作为被动参考染料的
在
mdck细胞中的病毒分离
解冻来自7只狗的每一只的冷冻的肺组织并在10倍体积的补充0.5%(bsa)和抗生素(庆大霉素和环丙沙星)的dulbecco改良的eagle培养基(dmem)中匀浆。离心除去固体残渣并将上清液接种到在补充1μg/mltpck-处理的胰蛋白酶(sigma-aldrichcorp.,st.louis,mo)和抗生素(庆大霉素和环丙沙星)的dmem中培养的madin-darby犬肾(mdck)细胞上。细胞在含有5%co2的湿润空气中37℃下在25cm2瓶中生长。每天观察培养物的形态学改变并在接种后5天收获。通过离心澄清收获的培养物并如对于最初接种所述的将上清液接种到新鲜的mdcm细胞上;对通过血细胞凝集或者rt-pcr没有显示流感病毒证据的样品进行两次额外的传代。使用0.5%火鸡细胞如以前描述(burleson,f.etal.,1992;kendal,p.etal.,1982)的测定澄清的上清液中的血细胞凝集活性。如下述进行rt-pcr。
含胚的鸡蛋中的病毒分离
如上文关于mdck细胞的接种所述的从冷冻的肺组织制备匀浆。将匀浆(0.2ml)接种到10天龄含胚的鸡蛋的尿膜囊中。在35℃培育48小时后,在4℃过夜冷冻鸡蛋,然后收获尿囊液。使用0.5%火鸡血红细胞如以前描述的(burleson,f.etal.,1992;kendal,p.etal.,1982)测定澄清的上清液中的血细胞凝集活性。如下文描述的进行rt-pcr。对最初接种后没有显示出流感病毒证据的样品用含胚的蛋进行两次额外传代。
rt-pcr、核苷酸测序和系统进化分析
使用
血细胞凝集抑制(hi)测定
将血清样品与受体破坏酶(rde,denkaseikenco.,ltd.,tokyo,japan)(1份血清:3份rde)在37℃温育16小时,然后在56℃热失活30分钟。流感a/canine/jacksonville/05(h3n8)病毒在37℃下5%co2中在mdck细胞中生长72小时。收获病毒培养上清液,通过离心澄清,并在-80℃保存。hi测定中使用的所有其他病毒都生长在10天龄的含胚的鸡蛋中,从其收集尿囊液并在-80℃保存。如以前描述的(kendal,p.etal.,1982)进行hi测定。简言之,向96孔塑料板中等体积的连续稀释的血清中加入25μl4凝血单位的病毒并在室温下温育30分钟。加入等体积的0.5%火鸡红细胞并在30分钟后通过视觉估计血细胞凝集效价。将终点hi效价定义为完全抑制血细胞凝集的血清的最后稀释度。
实施例7─临床病例
在2005年4月和5月,在佛罗里达东北部的收容所中喂养的狗中发生了以前描述的呼吸系统疾病爆发(crawford,p.c.etal.,2005)。该爆发涉及3个月至9岁年龄的至少58条狗,并且包括纯种狗以及杂种狗。最常见的临床病征是脓性鼻分泌物和咳嗽7到21天。在具有临床疾病≥7天的43条狗中,41条对canine/fl/04(h3n8)的hi抗体效价为32到>1024。至少10条狗发展成肺炎,其中6条被实施安乐死。这6条杂种狗包括3条雄性和3条雌性,年龄为4个月到3岁。在安乐死时临床病征的持续时间为2到10天。在尸体剖检时,这些狗具有肺充血和水肿。对呼吸道的组织学检查揭示了鼻炎、气管炎、支气管炎、细支气管炎和化脓性支气管肺炎。在气管、支气管、细支气管和支气管腺中存在上皮细胞坏死和糜烂。呼吸系统组织被嗜中性粒细胞和巨噬细胞浸润。
在2005年5月,在佛罗里达东南部的一个兽医诊所中40条宠物狗中发生呼吸系统疾病爆发。最常见的临床病征是脓性鼻分泌物和咳嗽10到30天。在40条狗中,17条对于canine/fl/04(h3n8)是血清阳性的,hi抗体效价范围为32到>1024。在可以得到配对的急性和恢复期血清的10条狗中发生了血清转变。三条狗发展为肺炎。一条狗为9岁的雄性yorkshireterrier,在临床病征发作后3天死亡。该狗具有气管支气管炎、肺水肿和充血,和严重的支气管肺炎。类似于6条收容所的狗,在组织中有上皮细胞坏死和气道糜烂和嗜中性粒细胞浸润。
实施例8─实时rt-pcr和病毒分离
通过定量实时rt-pcr测定法分析来自7条狗的肺组织,所述测定法检测甲型流感的m基因和犬h3n8甲型流感病毒的h3基因。来自所有7条狗的肺对于甲型流感m基因和犬流感h3基因都是阳性的(表8)。在mdck细胞中传代3次后,从在肺炎3天后死亡的收容所狗的肺分离亚型h3n8病毒。该病毒称作a/canine/jacksonville/05(h3n8)(canine/jax/05)。在含胚的鸡蛋中传代2次后,从肺炎3天后也死亡的宠物狗的肺回收甲型流感亚型h3n8病毒。将该病毒称作a/canine/miami//05(h3n8)(canine/miami/05)。
实施例9─犬甲型流感h3n8分离群的遗传学分析
canine/jax/05和canine/miami/05的序列分析揭示它们的血凝素(ha)基因与从2004和2005年赛场的流感爆发期间死于肺炎的竞赛灵
实施例10─犬甲型流感病毒h3n8分离群的氨基酸分析
在所有6种犬分离群中都有保守氨基酸替代,其使得它们与同时代的马流感病毒不同(表9)。这些保守替代是i15m、n83s、w222l、i328t和n483t。成熟ha蛋白质的系统发生比较表明canine/jax/05、canine/miami/05和canine/iowa/05病毒与canine/tx/04分离群形成一个亚组(图4)。有3个氨基酸改变(l118v、k261n和g479e)使得该亚组与其他犬病毒不同(表9)。有两个氨基酸改变(f79l和g218e),其使得2005分离群与它们的canine/tx/04根不同。此外,来自非灵
实施例11─犬甲型流感h3n8分离群的抗原分析
使用较早的和同时代的马流感病毒和犬流感病毒的血清组,和在2005年从感染流感病毒的马和狗收集的血清进行血细胞凝集抑制(hi)试验(表10)。在该分析中还包括来自对canine/fl/04免疫的白鼬的血清。当用同时代的马病毒测试时,马血清中hi抗体效价比以前的分离群高8到16倍,但是当用犬病毒测试时降低至少4倍。犬血清不与较早的马病毒反应,但是当用同时代的马分离群和犬分离群测试时,抗体效价增加4倍。该结果也在来自对犬流感病毒免疫的白鼬的血清中观察到。这些血清反应性模式表明犬流感病毒和同时代的马流感病毒之间的抗原相似性,并且与系统发生分析相一致。抗canine/miami/05分离群的马、犬和白鼬血清中的抗体效价与2003和2004白鼬分离群的那些相似。然而,canine/jax/05分离群的效价低2到4倍。这提示canine/jax/05在抗原上与其他犬分离群不同,这可能与成熟ha中107位的单个氨基酸改变部分有关。
a在用抗原栏中所列出的马、犬或者白鼬血清和病毒进行的血细胞凝集抑制测定中测定的抗体效价。
b来自用canine/fl/04病毒免疫的血清。
实施例12-15的材料和方法
犬流感病毒接种物
通过用代表以前描述的(crawfordetal.,2005)最初分离群的第3代的a/canine/fl/43/04(h3n8)原种接种madin-darby犬肾(mdck)上皮细胞,制备病毒接种物。在补充1μg/mltpck-处理的胰蛋白酶(sigma-aldrichcorp.,st.louis,mo)和抗生素(庆大霉素和环丙沙星)的dulbecco极限必需培养基(dmem)中接种的mdck细胞在含有5%co2的湿润空气中37℃下生长在250cm2培养瓶中。每天观察培养物的形态改变并在接种后5天收获。通过离心澄清收获的培养物并在接种狗之前将上清液在-80℃保存。用上清液的等分试样通过reed和muench方法测定病毒效价。效价为107半数组织培养感染量(tcid50)的a/canine/florida/43/04(canine/fl/04)/ml。
实验接种
8条4个月龄的colony品种的杂种狗(marshallbioresources,northrose,ny)(4条雄性和4条雌性)用于佛罗里达大学机构动物管理和使用委员会批准的实验接种研究。狗的体重为13到17kg。在接种前,根据体检、基线血试验和记录体温两周,发现狗是健康的。根据对在到达实验室之时和2周后收集的配对血清样品进行的血清学试验,所有狗以前都没有接触犬流感病毒。通过静脉内注射异丙酚(
咽和直肠拭子采集
为了监视病毒脱落,在接种后0到6天,使用聚酯拭子(fisherscientificinternationalinc.,pittsburgh,pa)从每条狗每天两次收集口咽样品。将拭子置于含有0.5%牛血清白蛋白(bsa)的1ml无菌磷酸缓冲盐水(pbs)中。从第0到6天每天从每条狗收集直肠拭子。通过离心澄清拭子运送培养液,制备拭子提取物。使用directigentm商业免疫测定试剂盒(bd,franklinlakes,nj)根据生产商的使用说明,对拭子提取物的等分试样立即测试甲型流感病毒核蛋白。剩余的提取物在-80℃保存备用于其他的病毒学测定。
尸体剖检
在接种后第1天,通过静脉内接种
免疫组织化学
将脱石蜡并再水化的5-μm气管和肺组织切片封固在bond-ritetm载玻片(richard-allanscientific,kalamazoo,mi)上并随后用蛋白酶k(dakocytomationinc.,carpenteria,ca)处理,接着用过氧化物酶封闭试剂(
来自拭子和组织的rna提取物
将来自每条狗的肺和气管组织解冻并在补充0.5%牛血清白蛋白(bsa)和抗生素(庆大霉素和环丙沙星)的极限必需培养基(mem)中,使用一次性组织研磨机(kendall,lifelinemedicalinc.,danbury,ct)匀浆。使用商业试剂盒(
实时rt-pcr
使用
对
从组织再次分离病毒
解冻来自接种病毒的狗的冷冻的肺和气管组织并在10倍体积的补充0.5%(bsa)和抗生素的dmem中匀浆。离心除去固体残渣并将上清液接种到在补充1μg/mltpck-处理的胰蛋白酶(sigma-aldrichcorp.,st.louis,mo)和如上述抗生素的dmem中培养的mdck细胞上。细胞在含有5%co2的湿润空气中37℃下在25cm2瓶中生长。每天观察培养物的形态学改变并在接种后5天收获。通过离心澄清收获的培养物并如对于最初接种所述的将上清液接种到新鲜的mdcm细胞上;对通过血细胞凝集或者rt-pcr没有显示流感病毒证据的样品进行两次额外的传代。使用0.5%火鸡细胞如以前描述(crawfordetal.,2005)的测定经澄清的上清液中的血细胞凝集活性。如下述进行rt-pcr。
rt-pcr、核苷酸测序和系统进化分析
使用
实施例12─临床疾病
所有6条接种病毒的狗在接种后前2天都产生了暂时发热(直肠温度≥39℃),但是没有一只在6天的观察期内显示出呼吸系统病征如咳嗽或者鼻涕。假接种的狗保持临床上健康。
实施例13─病毒脱落
对接种后24小时从一条接种病毒的狗收集的口咽拭子检测甲型流感核蛋白。通过定量实时rt-pcr,在接种后72、84和120小时从一条狗和接种后108、120和132小时从另一条狗收集的口咽拭子是病毒阳性的(表11)。每μl拭子提取物中流感m基因拷贝的绝对数目从接种后第3天到第6天随时间增加。在直肠拭子中没有检测到病毒。
实施例14─尸体剖检
与以前使用特定无病原体的小猎兔犬的实验感染(crawfordetal.,2005)相比,接种病毒的杂种狗患有肺炎,如通过来自接种后1到6天的肺的总体的和组织学分析所证明。除了肺炎外,狗还患有类似于自然感染的狗中所描述的鼻炎、气管炎、支气管炎和细支气管炎(crawfordetal.,2005)。在呼吸道和支气管腺层中存在上皮坏死和糜烂,在粘膜下层组织中有嗜酸性粒细胞和巨噬细胞浸润(图5,上图)。免疫组织化学在支气管、细支气管和支气管腺的上皮细胞中检测到病毒h3抗原(图5,下图)。不存在细菌超感染。来自2条假接种的狗的呼吸系统组织是正常的。
实施例15-气管和肺中的病毒复制
通过定量实时rt-pcr,从接种后第1天到第6天,所有狗中的气管和肺都是病毒阳性的(表12)。每μl气管匀浆的流感m基因拷贝的绝对数目从接种后第1天到第5天增加,然后在第6天下降。每μl肺匀浆的m基因拷贝的绝对数目从接种后第1天到第6天下降。通常,在接种后6天的每天,气管含有比肺多≥1log10的病毒。
a用a/canine/fl/43/04(h3n8)病毒接种后从狗收集口咽拭子的时间。
b通过将m(ct)除以每个拭子提取物的gapdh(ct)计算归一化比。
c每μl拭子提取物的基质基因拷贝的绝对数目。
a用a/canine/fl/43/04(h3n8)病毒接种后从狗收集组织的时间。
b通过将m(ct)除以每个组织匀浆的gapdh(ct)计算归一化比。
c每μl组织匀浆的基质基因拷贝的绝对数目。
实施例16的材料和实施例方法
病毒毒株
在含胚的卵或者mdck细胞中增殖犬流感病毒毒株以及鸟、马和人来源的那些流感病毒毒株(表15中所列),并通过鸡胚中的终点稀释或者噬斑测定法滴定它们的感染力。使用火鸡血红细胞通过血细胞凝集测定法进行快速病毒定量。
诊断样品
对2005年期间病毒呼吸系统疾病的疑似病例收集的共60条犬的肺组织测试犬流感病毒的存在。
从犬组织样品提取rna
将重量为20到30mg的肺组织块在一次性组织研磨机(kendal)中匀浆。按照生产商的推荐,使用商业试剂盒(rneasyminikit,qiagen,valencia,ca)提取总rna并用终体积60μl稀释。
引物和探针设计
使用clustalx程序(版本1.8)进行来自多种亚型和来自多种物种的h3和m基因的多序列比对。从对应于甲型流感病毒的不同亚型的已知序列的保守区选择基质(m)引物和探针,而选择h3血凝素基因特异引物和探针组以特别匹配马和犬甲型流感病毒基因和错配同源的鸟和人基因(表13)。用引物设计软件(oligos版本9.1)和exiqon(http://lnatools.com)提供的基于网络的分析工具进行tm计算和预测二级结构以及自身杂交。18srrna基因的保守区用作从犬组织样品的提取的rna的存在的内源性内部对照。pre-developed
实时rt-pcr条件
通过使用含有作为被动参照染料的rox的quantitectprobert-pcr试剂盒(qiagen,valencia,ca)进行一步实时rt-pcr。在每次实时rt-pcr反应中,5μlrna样品用作模板与反应混合物组合,所述反应混合物含有10μl2xquantitechprobert-pcrmastermix,0.2μlquantitechrtmix,引物(0.4μm终浓度的h3基因或者0.6μm终浓度的m基因),探针(0.1μm终浓度的h3基因或者0.2μm终浓度的m基因)和无rna酶的水,最终体积为20μl。在mx3005preal-timeqpcr系统(stratagene)中进行一步实时rt-pcr。循环条件包括50℃30分钟的反转录步骤。95℃15分钟以便活化hotstartaqdna聚合酶的初步变性步骤后,在40个循环中进行扩增,每个循环包括变性(94℃15秒)和退火/延伸(60℃30秒)。在每个循环延伸步骤结束时得到fam(发射波长516nm,用于h3和m检测)和vic(发射波长555nm,用于18srrna检测)荧光信号一次。使用mx3005p软件版本2.02(stratagene)进行实时pcr测定的数据采集和分析。
h3引物/探针组对于犬流感(h3n8)的特异性和m引物/探针组对于甲型流感病毒的通用性
为了测试每种引物/探针组的特异性,从甲型流感病毒的几种已知的亚型提取的rna用作实时rt-pcr测定中的模板(表15)。
用于确定实时rt-pcr性能的rna标准
通过使用与t7启动子连接的引物,用犬甲型流感病毒(a/canine/florida/242/2003(h3n8))的基因产生h3(nt1-487)和m(nt1-276)的pcr扩增子(表13)。然后通过使用riboprobe体外转录系统-t7(promega),按照生产商的推荐,将h3和m基因的纯化的pcr扩增子用作体外转录的模板。通过测量260nm的吸光度计算所转录的rna的浓度。然后将rna连续稀释10倍,从108到10个拷贝/μl以进行灵敏度测试。此外,通过将最初的rna模板浓度(拷贝/μl)的对数对为每次稀释得到的阈值循环数(ct)作图产生标准曲线,以便确定实时rt-pcr的总体性能。
实时rt-pcr和directigenflua测试试剂盒之间的比较灵敏度测试
将包括106.67eid50/ml(ha=64)的a/wyoming/3/2003(h3n2)和107.17eid50/ml(ha=16)的a/canine/florida/242/2003(h3n8)的两种病毒毒株的原种病毒用于检测阈值测定法。按照生产商的使用说明,在快速甲型流感病毒抗原检测试剂盒directigenflua,(becton,dickinsonandcompany)中使用磷酸缓冲盐水(pbs)(125μl)中样品的对数稀释度。每个directigenflua测试装置在膜中央具有一个h1n1流感抗原点,其显影为紫色点并且指出该测试的完整性,该测试是基于抗核蛋白(np)的单克隆抗体。在所述点周围紫色三角形的显影表明在测试的样品中存在流感np。将来自三角形的紫色信号的强度打分为+(三角形轮廓),++(浅色三角形),+++(深紫色三角形)和++++(极深紫色三角形)。使用qiaampviralrnamini试剂盒(qiagen,valencia,ca)从每种病毒稀释液的125μl等分试样提取病毒rna并以最终体积50μl稀释。通过实时rt-pcr测试5ul体积提取的病毒rna用于与directigenflua试剂盒的比较灵敏度测试。
实施例16
犬流感病毒的实时rt-pcr测定依赖于来自三种分子探针的信息,所述探针靶定来自宿主细胞的18srrna以及来自甲型流感病毒基因组的m和h3(表14)。宿主基因的扩增报告样品质量和完整性。预期含有犬流感(h3n8)病毒的临床的、尸体剖检或实验室样品用三种探针产生扩增信号。用m和18srrna探针产生扩增信号但是对于h3阴性的样品将表明来自人、猪或者鸟来源的流感病毒亚型h3或者来自非h3亚型的流感病毒。这些罕见的情况可以通过rt-pcr解决,其使用ha通用引物以产生扩增子cdna,可以通过测序分析所述cdna。适当收集和处理的缺少甲型流感病毒的样品仅仅产生18srrna扩增信号。仅仅18srrna探针和h3探针产生扩增信号的情况表明有缺点的技术,除非证明相反;需要阐明使用m探针的假阴性或者对于h3的假阳性。最后,用这三种探针不能产生扩增信号的样品表明有缺陷的样品收集、降解、错误的rna提取或者存在pcr中使用的聚合酶的抑制剂。
为了测试犬甲型流感病毒(h3n8)的h3引物/探针组的特异性和甲型流感的m引物/探针组的通用性,通过实时rt-pcr测试甲型流感病毒的几种亚型。结果表明h3引物/探针组仅仅用犬流感(h3n8)产生阳性扩增信号。在其他亚型或者人h3毒株中没有观察到显著的假阳性或者非特异性扩增信号。m引物/探针组对测试的所有毒株产生了阳性扩增信号(表15)。这些结果表明h3引物/探针特异检测犬甲型流感病毒(h3n8),而m引物/探针检测甲型流感病毒的多种亚型。
通过m和h3体外转录的rna的终点稀释评估实时rt-pcr测定法的性能。如所预期的,阈值循环数(ct)与rna标准品的稀释度以正相关增加。可以在m和h3的分别低至103和102个拷贝/μl的rna标准品稀释度下检测到荧光信号(图6a和6b)。通过将起始rna浓度的对数对从每个稀释度得到的阈值循环数(ct)作图,构建m和h3基因的标准曲线(图6c和6d)。用标准曲线的斜率确定pcr反应效率,其在理论上是指数的;100%扩增效率将意味着每个循环的扩增子浓度的加倍。具有约-3.1到-3.6之间斜率的标准曲线通常适于多数需要准确定量的应用(90-110%反应效率)。rsq值是所有数据对标准曲线图的拟合。如果所有数据都精确地位于曲线上,那么rsq将为1.00。随着数据从该曲线进一步下降,rsq降低。rsq≥0.985是多数测定法可接受的。m标准曲线揭示了-3.576的斜率(效率=90.4%)和rsq=1.00,而h3标准曲线产生了-3.423的斜率(效率=95.9%)和rsq=0.999。这些值表明实时rt-pcr测定法的满意的扩增效率和总体性能。我们将m引物/探针组与h3引物/探针组相比较低的效率和灵敏度规因于m引物序列的n倍简并性,需要该简并性来确保m基因序列变异性在多种亚型、宿主和谱系的病毒之间的宽覆盖度。
还将实时rt-pcr测定法的灵敏度与商业的快速抗原检测测定法(directigenflua)相比较。用directigenflua和通过实时rt-pcr分析了a/wyoming/3/2003(h3n2)和a/canine/florida/242/2003(h3n8)的对数稀释度。directigenflua的结果表明对两种病毒毒株的灵敏度为用于这些实验的原种病毒的约100倍稀释度(图7)。犬病毒(a/canine/florida/242/2003:106.xpfu/ml)样品产生的信号(紫色)比在人病毒(a/wyoming/3/2003:107.xpfu/ml)中发现的弱得多,与这些样品中较低的病毒浓度相一致。备选地,犬流感的较低信号可以规因于单克隆抗体对np的分子特异性;即在犬甲型流感病毒的np表位中氨基酸的保守性很差。
a/canine/florida/242/2003和a/wyoming/3/2003的每次反应分别使用病毒10和30pfu当量,m基因的实时rt-pcr产生了高于阈值的ct值(表16)。两种病毒毒株的灵敏度值的差异是因为最初的病毒滴定度的不同。没有进行犬和人流感病毒之间的h3基因检测比较,是因为我们的实时rt-pcr测定中的h3引物/探针唯一地扩增犬甲型流感病毒。rt-pcr比快速抗原检测试剂盒灵敏105倍。
为了评估rt-pcr测试在来自患有急性呼吸系统疾病的狗的尸体剖检样品中的性能,通过实时rt-pcr测试了在2005年送交的60个犬肺组织样品中犬甲型流感病毒的存在。60个样品中总共12个(20%)对于m和h3基因是阳性的,而剩下的48个样品对于m和h3基因都产生了阴性结果。通过蛋和mdck细胞接种进行病毒分离尝试,以评估实时测定法的特异性;根据rt-pcr,12个样品中对犬流感阳性的两个样品产生了犬流感病毒(数据未显示,手稿准备中)。尽管所有组织都从具有严重呼吸系统疾病史的狗中收集,但是通过实时pcr或者常规分离,多数样品都没有产生犬流感病毒,提示其他呼吸系统病原体如支气管博德特氏菌(bordetellabronchiseptica)、犬瘟热或者副流感病毒的高发生率。本文的一步实时rt-pcr测定法提供了犬甲型流感病毒(h3n8)检测的快速、灵敏和划算的方法。该疾病的早期中,犬甲型流感病毒(h3n8)感染的快速实验室诊断可以得到与临床患者和设施管理相关的信息。
*注意通过核苷酸测序证实临床样品的亚型。
*基于1963和1998年间分离的病毒的可利用的基因。
*基于1963和1998年间分离的病毒的可利用的基因。
*基于1963和1998年间分离的病毒的可利用的基因。
应该理解本文描述的实施例和实施方案仅用于阐明目的,并且参照其的多种修饰或更改将是本领域技术人员可以想到的,并且包括在本申请的精神和范围内。
参考文献
美国专利号5,106,739
美国专利号5,034,322
美国专利号6,455,760
美国专利号6,696,623
美国专利号4,683,202
美国专利号4,683,195
美国专利号4,800,159
美国专利号4,965,188
美国专利号5,994,056
美国专利号6,814,934
公布的美国专利申请号20040078841
公布的美国专利申请号20040067506
公布的美国专利申请号20040019934
公布的美国专利申请号20030177536
公布的美国专利申请号20030084486
公布的美国专利申请号20040123349
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序列表
<110>佛罗里达大学研究基金公司
<120>用于犬科动物中呼吸系统疾病控制的物质和方法
<130>uf-445xc1
<150>us60/673,443
<151>2005-04-21
<160>88
<170>patentin版本3.3
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<211>2277
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<213>流感病毒
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245250255
caaagtttaattattgcagcccggaacatagtgagaagagcgacagta816
glnserleuileilealaalaargasnilevalargargalathrval
260265270
tcagcagatccactagcatccctactggaaatgtgccacagtacacag864
seralaaspproleualaserleuleuglumetcyshisserthrgln
275280285
attggtggaataaggatggtagacatccttaagcagaatccaacagag912
ileglyglyileargmetvalaspileleulysglnasnprothrglu
290295300
gaacaagctgtggatatatgcaaagcagcaatgggattgagaattagc960
gluglnalavalaspilecyslysalaalametglyleuargileser
305310315320
tcatcattcagctttggtggattcaccttcaaaagaacaagtggatca1008
serserpheserpheglyglyphethrphelysargthrserglyser
325330335
tcagtcaagagagaagaagaaatgcttacgggcaaccttcaaacattg1056
servallysargglugluglumetleuthrglyasnleuglnthrleu
340345350
aaaataagagtgcatgagggctatgaagaattcacaatggtcggaaga1104
lysileargvalhisgluglytyrglugluphethrmetvalglyarg
355360365
agagcaacagccattatcaaaaaggcaaccagaagattgattcaattg1152
argalathralaileilelyslysalathrargargleuileglnleu
370375380
atagtaagtgggagagatgaacaatcaattgctgaagcaataattgta1200
ilevalserglyargaspgluglnserilealaglualaileileval
385390395400
gccatggtgttttcgcaagaagattgcatgataaaagcagttcgaggc1248
alametvalpheserglngluaspcysmetilelysalavalarggly
405410415
gatttgaactttgttaatagagcaaatcagcgtttgaaccccatgcat1296
aspleuasnphevalasnargalaasnglnargleuasnpromethis
420425430
caactcttgaggcatttccaaaaagatgcaaaagtgcttttccacaat1344
glnleuleuarghispheglnlysaspalalysvalleuphehisasn
435440445
tggggaattgaacccatcgacaatgtaatggggatgattggaatattg1392
trpglyilegluproileaspasnvalmetglymetileglyileleu
450455460
cctgacatgaccccaagcaccgagatgtcattgagaggagtgagagtc1440
proaspmetthrproserthrglumetserleuargglyvalargval
465470475480
agcaaaatgggagtggatgagtactccagcactgagagagtggtggtg1488
serlysmetglyvalaspglutyrserserthrgluargvalvalval
485490495
agcattgaccgttttttaagagttcgggatcaaaggggaaacatacta1536
serileaspargpheleuargvalargaspglnargglyasnileleu
500505510
ctgtcccctgaagaagtcagtgaaacacaaggaacggaaaagctgaca1584
leuserproglugluvalsergluthrglnglythrglulysleuthr
515520525
ataatttattcgtcatcaatgatgtgggagattaatggtcccgaatca1632
ileiletyrsersersermetmettrpgluileasnglyprogluser
530535540
gtgttggtcaatacttatcaatggatcatcaggaactgggaaattgta1680
valleuvalasnthrtyrglntrpileileargasntrpgluileval
545550555560
aaaattcagtggtcacaggaccccacaatgttatacaataagatagaa1728
lysileglntrpserglnaspprothrmetleutyrasnlysileglu
565570575
tttgagccattccaatccctggtccctagggccaccagaagccaatac1776
pheglupropheglnserleuvalproargalathrargserglntyr
580585590
agcggtttcgtaagaaccctgtttcagcaaatgcgagatgtacttgga1824
serglyphevalargthrleupheglnglnmetargaspvalleugly
595600605
acatttgatactgctcaaataataaaactcctcccttttgccgctgct1872
thrpheaspthralaglnileilelysleuleuprophealaalaala
610615620
cctccggaacagagtaggatgcagttctcttctttgactgttaatgta1920
proprogluglnserargmetglnpheserserleuthrvalasnval
625630635640
agaggttcgggaatgaggatacttgtaagaggcaattccccagtgttc1968
argglyserglymetargileleuvalargglyasnserprovalphe
645650655
aactacaataaagccactaaaaggctcacagtcctcggaaaggatgca2016
asntyrasnlysalathrlysargleuthrvalleuglylysaspala
660665670
ggtgcgcttactgaggacccagatgaaggtacggctggagtagaatct2064
glyalaleuthrgluaspproaspgluglythralaglyvalgluser
675680685
gctgttctaagagggtttctcattttaggtaaagagaacaagagatat2112
alavalleuargglypheleuileleuglylysgluasnlysargtyr
690695700
ggcccagcactaagcatcaatgaactaagcaaacttgcaaaaggggag2160
glyproalaleuserileasngluleuserlysleualalysglyglu
705710715720
aaagccaatgtactaattgggcaaggggacgtagtgttggtaatgaaa2208
lysalaasnvalleuileglyglnglyaspvalvalleuvalmetlys
725730735
cggaaacgtgactctagcatacttactgacagccagacagcgaccaaa2256
arglysargaspserserileleuthraspserglnthralathrlys
740745750
aggattcggatggccatcaat2277
argileargmetalaileasn
755
<210>2
<211>759
<212>prt
<213>流感病毒
<400>2
metgluargileglugluleuargaspleumetleuglnserargthr
151015
arggluileleuthrlysthrthrvalasphismetalaileilelys
202530
lystyrthrsergluargglnglulysasnproalaleuargmetlys
354045
trpmetmetalametlystyrproilethralaasplysargilemet
505560
glumetileprogluargasngluglnglyglnthrleutrpserlys
65707580
thrasnaspalaglyseraspargvalmetvalserproleualaval
859095
thrtrptrpasnargasnglyprothrthrserthrilehistyrpro
100105110
lysvaltyrlysthrtyrpheglulysvalgluargleulyshisgly
115120125
thrpheglyprovalhispheargasnglnvallysileargargarg
130135140
valaspvalasnproglyhisalaaspleuseralalysglualagln
145150155160
aspvalilemetgluvalvalpheproasngluvalglyalaileile
165170175
leuthrsergluserglnleuthrilethrlysglulyslysgluglu
180185190
leuglnaspcyslysilealaproleumetvalalatyrmetleuglu
195200205
arggluleuvalarglysthrargpheleuprovalalaglyglythr
210215220
serservaltyrilegluvalleuhisleuthrglnglythrcystrp
225230235240
gluglnmettyrthrproglyglygluvalargasnaspaspileasp
245250255
glnserleuileilealaalaargasnilevalargargalathrval
260265270
seralaaspproleualaserleuleuglumetcyshisserthrgln
275280285
ileglyglyileargmetvalaspileleulysglnasnprothrglu
290295300
gluglnalavalaspilecyslysalaalametglyleuargileser
305310315320
serserpheserpheglyglyphethrphelysargthrserglyser
325330335
servallysargglugluglumetleuthrglyasnleuglnthrleu
340345350
lysileargvalhisgluglytyrglugluphethrmetvalglyarg
355360365
argalathralaileilelyslysalathrargargleuileglnleu
370375380
ilevalserglyargaspgluglnserilealaglualaileileval
385390395400
alametvalpheserglngluaspcysmetilelysalavalarggly
405410415
aspleuasnphevalasnargalaasnglnargleuasnpromethis
420425430
glnleuleuarghispheglnlysaspalalysvalleuphehisasn
435440445
trpglyilegluproileaspasnvalmetglymetileglyileleu
450455460
proaspmetthrproserthrglumetserleuargglyvalargval
465470475480
serlysmetglyvalaspglutyrserserthrgluargvalvalval
485490495
serileaspargpheleuargvalargaspglnargglyasnileleu
500505510
leuserproglugluvalsergluthrglnglythrglulysleuthr
515520525
ileiletyrsersersermetmettrpgluileasnglyprogluser
530535540
valleuvalasnthrtyrglntrpileileargasntrpgluileval
545550555560
lysileglntrpserglnaspprothrmetleutyrasnlysileglu
565570575
pheglupropheglnserleuvalproargalathrargserglntyr
580585590
serglyphevalargthrleupheglnglnmetargaspvalleugly
595600605
thrpheaspthralaglnileilelysleuleuprophealaalaala
610615620
proprogluglnserargmetglnpheserserleuthrvalasnval
625630635640
argglyserglymetargileleuvalargglyasnserprovalphe
645650655
asntyrasnlysalathrlysargleuthrvalleuglylysaspala
660665670
glyalaleuthrgluaspproaspgluglythralaglyvalgluser
675680685
alavalleuargglypheleuileleuglylysgluasnlysargtyr
690695700
glyproalaleuserileasngluleuserlysleualalysglyglu
705710715720
lysalaasnvalleuileglyglnglyaspvalvalleuvalmetlys
725730735
arglysargaspserserileleuthraspserglnthralathrlys
740745750
argileargmetalaileasn
755
<210>3
<211>2274
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(2274)
<400>3
atggatgtcaatccgactctactcttcttaaaggtgccagcgcagaat48
metaspvalasnprothrleuleupheleulysvalproalaglnasn
151015
gctataagcacaacattcccttatactggagatcctccctacagtcat96
alaileserthrthrpheprotyrthrglyaspproprotyrserhis
202530
ggaacagggacaggatacaccatggatactgtcaacagaacacaccaa144
glythrglythrglytyrthrmetaspthrvalasnargthrhisgln
354045
tattcagaaaaagggaaatggacaacaaacactgagattggagcacca192
tyrserglulysglylystrpthrthrasnthrgluileglyalapro
505560
caacttaatccaatcgatggaccacttcctgaagacaatgaaccaagc240
glnleuasnproileaspglyproleuprogluaspasngluproser
65707580
gggtacgcccaaacagattgtgtattggaagcaatggctttccttgaa288
glytyralaglnthraspcysvalleuglualametalapheleuglu
859095
gaatcccatccaggaatctttgaaaattcgtgtcttgaaacgatggag336
gluserhisproglyilephegluasnsercysleugluthrmetglu
100105110
gtgattcagcagacaagagtggacaaactaacacaaggccgacaaact384
valileglnglnthrargvalasplysleuthrglnglyargglnthr
115120125
tatgattggaccttgaataggaatcaacctgccgcaacagcacttgct432
tyrasptrpthrleuasnargasnglnproalaalathralaleuala
130135140
aatacgattgaagtattcagatcaaatggtctgacttccaatgaatcg480
asnthrilegluvalpheargserasnglyleuthrserasngluser
145150155160
gggagattgatggacttcctcaaagatgtcatggagtccatgaacaag528
glyargleumetasppheleulysaspvalmetglusermetasnlys
165170175
gaagaaatggaaataacaacacacttccaacggaagagaagagtaaga576
gluglumetgluilethrthrhispheglnarglysargargvalarg
180185190
gacaacatgacaaagagaatggtaacacagagaaccatagggaagaaa624
aspasnmetthrlysargmetvalthrglnargthrileglylyslys
195200205
aaacaacgattaaacagaaagagctatctaatcagaacattaacccta672
lysglnargleuasnarglyssertyrleuileargthrleuthrleu
210215220
aacacaatgaccaaggacgctgagagagggaaattgaaacgacgagca720
asnthrmetthrlysaspalagluargglylysleulysargargala
225230235240
atcgctaccccagggatgcagataagagggtttgtatattttgttgaa768
ilealathrproglymetglnileargglyphevaltyrphevalglu
245250255
acactagctcgaagaatatgtgaaaagcttgaacaatcaggattgcca816
thrleualaargargilecysglulysleugluglnserglyleupro
260265270
gttggcggtaatgagaaaaaggccaaactggctaatgtcgtcagaaaa864
valglyglyasnglulyslysalalysleualaasnvalvalarglys
275280285
atgatgactaattcccaagacactgaactctccttcaccatcactggg912
metmetthrasnserglnaspthrgluleuserphethrilethrgly
290295300
gacaataccaaatggaatgaaaatcagaacccacgcatattcctggca960
aspasnthrlystrpasngluasnglnasnproargilepheleuala
305310315320
atgatcacatacataactagaaaccagccagaatggttcagaaatgtt1008
metilethrtyrilethrargasnglnproglutrppheargasnval
325330335
ctaagcattgcaccgattatgttctcaaataaaatggcaagactgggg1056
leuserilealaproilemetpheserasnlysmetalaargleugly
340345350
aaaggatatatgtttgaaagcaaaagtatgaaattgagaactcaaata1104
lysglytyrmetphegluserlyssermetlysleuargthrglnile
355360365
ccagcagaaatgctagcaagcattgacctaaaatatttcaatgattca1152
proalaglumetleualaserileaspleulystyrpheasnaspser
370375380
acaaaaaagaaaattgagaagatacgaccacttctggttgacgggact1200
thrlyslyslysileglulysileargproleuleuvalaspglythr
385390395400
gcttcactgagtcctggcatgatgatgggaatgttcaacatgttgagc1248
alaserleuserproglymetmetmetglymetpheasnmetleuser
405410415
actgtgctgggtgtatccatattaaacctgggccagaggaaatacaca1296
thrvalleuglyvalserileleuasnleuglyglnarglystyrthr
420425430
aagaccacatactggtgggatggtctgcaatcatccgatgactttgct1344
lysthrthrtyrtrptrpaspglyleuglnserseraspasppheala
435440445
ttgatagtgaatgcgcctaatcatgaaggagtacaagctggagtagac1392
leuilevalasnalaproasnhisgluglyvalglnalaglyvalasp
450455460
agattctatagaacttgcaaactggtcgggatcaacatgagcaaaaag1440
argphetyrargthrcyslysleuvalglyileasnmetserlyslys
465470475480
aagtcctacataaatagaactggaacattcgaattcacaagctttttc1488
lyssertyrileasnargthrglythrphegluphethrserphephe
485490495
taccggtatggttttgtagccaatttcagcatggaactacccagtttt1536
tyrargtyrglyphevalalaasnphesermetgluleuproserphe
500505510
ggggtttccggaataaatgaatctgcagacatgagcattggagtgaca1584
glyvalserglyileasngluseralaaspmetserileglyvalthr
515520525
gtcatcaaaaacaacatgataaataatgatctcggtcctgccacggca1632
valilelysasnasnmetileasnasnaspleuglyproalathrala
530535540
caaatggcactccaactcttcattaaggattatcggtacacataccgg1680
glnmetalaleuglnleupheilelysasptyrargtyrthrtyrarg
545550555560
tgccatagaggtgatacccagatacaaaccagaagatcttttgagttg1728
cyshisargglyaspthrglnileglnthrargargserphegluleu
565570575
aagaaactgtgggaacagactcgatcaaagactggtctactggtatca1776
lyslysleutrpgluglnthrargserlysthrglyleuleuvalser
580585590
gatgggggtccaaacctatataacatcagaaacctacacatcccggaa1824
aspglyglyproasnleutyrasnileargasnleuhisileproglu
595600605
gtctgtttaaaatgggagctaatggatgaagattataaggggaggcta1872
valcysleulystrpgluleumetaspgluasptyrlysglyargleu
610615620
tgcaatccattgaatcctttcgttagtcacaaagaaattgaatcagtc1920
cysasnproleuasnprophevalserhislysgluilegluserval
625630635640
aacagtgcagtagtaatgcctgcgcatggccctgccaaaagcatggag1968
asnseralavalvalmetproalahisglyproalalyssermetglu
645650655
tatgatgctgttgcaacaacacattcttggatccccaagaggaaccgg2016
tyraspalavalalathrthrhissertrpileprolysargasnarg
660665670
tccatattgaacacaagccaaaggggagtactcgaagatgagcagatg2064
serileleuasnthrserglnargglyvalleugluaspgluglnmet
675680685
tatcagaaatgctgcaacctgtttgaaaaattcttccccagcagctca2112
tyrglnlyscyscysasnleupheglulysphepheproserserser
690695700
tacagaagaccagtcggaatttctagtatggttgaggccatggtgtcc2160
tyrargargprovalglyilesersermetvalglualametvalser
705710715720
agggcccgcattgatgcacgaattgacttcgaatctggacggataaag2208
argalaargileaspalaargileaspphegluserglyargilelys
725730735
aaggatgagttcgctgagatcatgaagatctgttccaccattgaagag2256
lysaspgluphealagluilemetlysilecysserthrilegluglu
740745750
ctcagacggcaaaaatag2274
leuargargglnlys
755
<210>4
<211>757
<212>prt
<213>流感病毒
<400>4
metaspvalasnprothrleuleupheleulysvalproalaglnasn
151015
alaileserthrthrpheprotyrthrglyaspproprotyrserhis
202530
glythrglythrglytyrthrmetaspthrvalasnargthrhisgln
354045
tyrserglulysglylystrpthrthrasnthrgluileglyalapro
505560
glnleuasnproileaspglyproleuprogluaspasngluproser
65707580
glytyralaglnthraspcysvalleuglualametalapheleuglu
859095
gluserhisproglyilephegluasnsercysleugluthrmetglu
100105110
valileglnglnthrargvalasplysleuthrglnglyargglnthr
115120125
tyrasptrpthrleuasnargasnglnproalaalathralaleuala
130135140
asnthrilegluvalpheargserasnglyleuthrserasngluser
145150155160
glyargleumetasppheleulysaspvalmetglusermetasnlys
165170175
gluglumetgluilethrthrhispheglnarglysargargvalarg
180185190
aspasnmetthrlysargmetvalthrglnargthrileglylyslys
195200205
lysglnargleuasnarglyssertyrleuileargthrleuthrleu
210215220
asnthrmetthrlysaspalagluargglylysleulysargargala
225230235240
ilealathrproglymetglnileargglyphevaltyrphevalglu
245250255
thrleualaargargilecysglulysleugluglnserglyleupro
260265270
valglyglyasnglulyslysalalysleualaasnvalvalarglys
275280285
metmetthrasnserglnaspthrgluleuserphethrilethrgly
290295300
aspasnthrlystrpasngluasnglnasnproargilepheleuala
305310315320
metilethrtyrilethrargasnglnproglutrppheargasnval
325330335
leuserilealaproilemetpheserasnlysmetalaargleugly
340345350
lysglytyrmetphegluserlyssermetlysleuargthrglnile
355360365
proalaglumetleualaserileaspleulystyrpheasnaspser
370375380
thrlyslyslysileglulysileargproleuleuvalaspglythr
385390395400
alaserleuserproglymetmetmetglymetpheasnmetleuser
405410415
thrvalleuglyvalserileleuasnleuglyglnarglystyrthr
420425430
lysthrthrtyrtrptrpaspglyleuglnserseraspasppheala
435440445
leuilevalasnalaproasnhisgluglyvalglnalaglyvalasp
450455460
argphetyrargthrcyslysleuvalglyileasnmetserlyslys
465470475480
lyssertyrileasnargthrglythrphegluphethrserphephe
485490495
tyrargtyrglyphevalalaasnphesermetgluleuproserphe
500505510
glyvalserglyileasngluseralaaspmetserileglyvalthr
515520525
valilelysasnasnmetileasnasnaspleuglyproalathrala
530535540
glnmetalaleuglnleupheilelysasptyrargtyrthrtyrarg
545550555560
cyshisargglyaspthrglnileglnthrargargserphegluleu
565570575
lyslysleutrpgluglnthrargserlysthrglyleuleuvalser
580585590
aspglyglyproasnleutyrasnileargasnleuhisileproglu
595600605
valcysleulystrpgluleumetaspgluasptyrlysglyargleu
610615620
cysasnproleuasnprophevalserhislysgluilegluserval
625630635640
asnseralavalvalmetproalahisglyproalalyssermetglu
645650655
tyraspalavalalathrthrhissertrpileprolysargasnarg
660665670
serileleuasnthrserglnargglyvalleugluaspgluglnmet
675680685
tyrglnlyscyscysasnleupheglulysphepheproserserser
690695700
tyrargargprovalglyilesersermetvalglualametvalser
705710715720
argalaargileaspalaargileaspphegluserglyargilelys
725730735
lysaspgluphealagluilemetlysilecysserthrilegluglu
740745750
leuargargglnlys
755
<210>5
<211>2151
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(2151)
<400>5
atggaagactttgtgcgacagtgcttcaatccaatgatcgtcgagctt48
metgluaspphevalargglncyspheasnprometilevalgluleu
151015
gcggaaaaggcaatgaaagaatatggagagaacccgaaaatcgaaaca96
alaglulysalametlysglutyrglygluasnprolysilegluthr
202530
aacaaatttgcagcaatatgcactcacttggaagtctgcttcatgtac144
asnlysphealaalailecysthrhisleugluvalcysphemettyr
354045
tcggattttcactttattaatgaactgggtgagtcagtggtcatagag192
seraspphehispheileasngluleuglygluservalvalileglu
505560
tctggtgacccaaatgctcttttgaaacacagatttgaaatcattgag240
serglyaspproasnalaleuleulyshisargphegluileileglu
65707580
gggagagatcgaacaatggcatggacagtagtaaacagcatctgcaac288
glyargaspargthrmetalatrpthrvalvalasnserilecysasn
859095
accacaagagctgaaaaacctaaatttcttccagatttatacgactat336
thrthrargalaglulysprolyspheleuproaspleutyrasptyr
100105110
aaggagaacagatttgttgaaattggtgtgacaaggagagaagttcac384
lysgluasnargphevalgluileglyvalthrargarggluvalhis
115120125
atatactacctggagaaggccaacaaaataaagtctgagaaaacacat432
iletyrtyrleuglulysalaasnlysilelysserglulysthrhis
130135140
atccacattttctcatttacaggagaggaaatggctacaaaagcggac480
ilehisilepheserphethrglygluglumetalathrlysalaasp
145150155160
tatactcttgatgaagagagtagagccaggatcaagaccagactattc528
tyrthrleuaspglugluserargalaargilelysthrargleuphe
165170175
accataagacaagaaatggccagtagaggcctctgggattcctttcgt576
thrileargglnglumetalaserargglyleutrpaspserphearg
180185190
cagtccgagagaggcgaagagacaattgaagaaagatttgaaataaca624
glnsergluargglyglugluthrileglugluargphegluilethr
195200205
gggacgatgcgcaagcttgccaattacagtctcccaccgaacttctcc672
glythrmetarglysleualaasntyrserleuproproasnpheser
210215220
agccttgaaaattttagagtctatgtggatggattcgaaccgaacggc720
serleugluasnpheargvaltyrvalaspglyphegluproasngly
225230235240
tgcattgagagtaagctttctcaaatgtccaaagaagtaaatgccaga768
cysilegluserlysleuserglnmetserlysgluvalasnalaarg
245250255
atcgaaccattttcaaagacaacaccccgaccactcaaaatgccaggt816
ileglupropheserlysthrthrproargproleulysmetprogly
260265270
ggtccaccctgccatcagcgatctaaattcttgctaatggatgctctg864
glyproprocyshisglnargserlyspheleuleumetaspalaleu
275280285
aaactgagcattgaggacccaagtcacgagggagagggaataccacta912
lysleuserilegluaspproserhisgluglygluglyileproleu
290295300
tatgatgcaatcaaatgcatgaaaactttctttggatggaaagagccc960
tyraspalailelyscysmetlysthrphepheglytrplysglupro
305310315320
agtattgttaaaccacatgaaaagggtataaacccgaactatctccaa1008
serilevallysprohisglulysglyileasnproasntyrleugln
325330335
acttggaagcaagtattagaagaaatacaagaccttgagaacgaagaa1056
thrtrplysglnvalleuglugluileglnaspleugluasngluglu
340345350
aggacccccaagaccaagaatatgaaaaaaacaagccaattgaaatgg1104
argthrprolysthrlysasnmetlyslysthrserglnleulystrp
355360365
gcactaggtgaaaatatggcaccagagaaagtggattttgaggattgt1152
alaleuglygluasnmetalaproglulysvalaspphegluaspcys
370375380
aaagacatcaatgatttaaaacaatatgacagtgatgagccagaagca1200
lysaspileasnaspleulysglntyraspseraspgluprogluala
385390395400
aggtctcttgcaagttggattcaaagtgagttcaacaaagcttgtgag1248
argserleualasertrpileglnserglupheasnlysalacysglu
405410415
ctgacagattcaagctggatagagctcgatgaaattggggaggatgtc1296
leuthraspsersertrpilegluleuaspgluileglygluaspval
420425430
gccccaatagaatacattgcgagcatgaggagaaattattttactgct1344
alaproileglutyrilealasermetargargasntyrphethrala
435440445
gagatttcccattgtagagcaacagaatatataataaaaggagtgtac1392
gluileserhiscysargalathrglutyrileilelysglyvaltyr
450455460
atcaacactgctctactcaatgcatcctgtgctgcgatggatgaattt1440
ileasnthralaleuleuasnalasercysalaalametaspgluphe
465470475480
caattaattccgatgataagtaaatgcaggaccaaagaagggagaagg1488
glnleuileprometileserlyscysargthrlysgluglyargarg
485490495
aaaacaaatttatatggattcataataaagggaaggtcccatttaaga1536
lysthrasnleutyrglypheileilelysglyargserhisleuarg
500505510
aatgatactgacgtggtgaactttgtaagtatggaattttctctcact1584
asnaspthraspvalvalasnphevalsermetglupheserleuthr
515520525
gatccaagatttgagccacacaaatgggaaaaatactgcgttctagaa1632
aspproargphegluprohislystrpglulystyrcysvalleuglu
530535540
attggagacatgcttctaagaactgctgtaggtcaagtgtcaagaccc1680
ileglyaspmetleuleuargthralavalglyglnvalserargpro
545550555560
atgtttttgtatgtaaggacaaatggaacctctaaaattaaaatgaaa1728
metpheleutyrvalargthrasnglythrserlysilelysmetlys
565570575
tggggaatggaaatgaggcgctgcctccttcagtctctgcaacagatt1776
trpglymetglumetargargcysleuleuglnserleuglnglnile
580585590
gaaagcatgatcgaagctgagtcctcagtcaaagaaaaggacatgacc1824
glusermetileglualagluserservallysglulysaspmetthr
595600605
aaagaattttttgagaacaaatcagagacatggcctataggagagtcc1872
lysgluphephegluasnlyssergluthrtrpproileglygluser
610615620
cccaaaggagtggaagagggctcaatcgggaaggtttgcaggacctta1920
prolysglyvalglugluglyserileglylysvalcysargthrleu
625630635640
ttagcaaaatctgtgtttaacagtttatatgcatctccacaactggaa1968
leualalysservalpheasnserleutyralaserproglnleuglu
645650655
gggttttcagctgaatctaggaaattacttctcattgttcaggctctt2016
glypheseralagluserarglysleuleuleuilevalglnalaleu
660665670
aaggatgacctggaacctggaacctttgatattggggggttatatgaa2064
lysaspaspleugluproglythrpheaspileglyglyleutyrglu
675680685
tcaattgaggagtgcctgattaatgatccctgggttttgcttaatgca2112
serilegluglucysleuileasnaspprotrpvalleuleuasnala
690695700
tcttggttcaactccttccttacacatgcactgaagtag2151
sertrppheasnserpheleuthrhisalaleulys
705710715
<210>6
<211>716
<212>prt
<213>流感病毒
<400>6
metgluaspphevalargglncyspheasnprometilevalgluleu
151015
alaglulysalametlysglutyrglygluasnprolysilegluthr
202530
asnlysphealaalailecysthrhisleugluvalcysphemettyr
354045
seraspphehispheileasngluleuglygluservalvalileglu
505560
serglyaspproasnalaleuleulyshisargphegluileileglu
65707580
glyargaspargthrmetalatrpthrvalvalasnserilecysasn
859095
thrthrargalaglulysprolyspheleuproaspleutyrasptyr
100105110
lysgluasnargphevalgluileglyvalthrargarggluvalhis
115120125
iletyrtyrleuglulysalaasnlysilelysserglulysthrhis
130135140
ilehisilepheserphethrglygluglumetalathrlysalaasp
145150155160
tyrthrleuaspglugluserargalaargilelysthrargleuphe
165170175
thrileargglnglumetalaserargglyleutrpaspserphearg
180185190
glnsergluargglyglugluthrileglugluargphegluilethr
195200205
glythrmetarglysleualaasntyrserleuproproasnpheser
210215220
serleugluasnpheargvaltyrvalaspglyphegluproasngly
225230235240
cysilegluserlysleuserglnmetserlysgluvalasnalaarg
245250255
ileglupropheserlysthrthrproargproleulysmetprogly
260265270
glyproprocyshisglnargserlyspheleuleumetaspalaleu
275280285
lysleuserilegluaspproserhisgluglygluglyileproleu
290295300
tyraspalailelyscysmetlysthrphepheglytrplysglupro
305310315320
serilevallysprohisglulysglyileasnproasntyrleugln
325330335
thrtrplysglnvalleuglugluileglnaspleugluasngluglu
340345350
argthrprolysthrlysasnmetlyslysthrserglnleulystrp
355360365
alaleuglygluasnmetalaproglulysvalaspphegluaspcys
370375380
lysaspileasnaspleulysglntyraspseraspgluprogluala
385390395400
argserleualasertrpileglnserglupheasnlysalacysglu
405410415
leuthraspsersertrpilegluleuaspgluileglygluaspval
420425430
alaproileglutyrilealasermetargargasntyrphethrala
435440445
gluileserhiscysargalathrglutyrileilelysglyvaltyr
450455460
ileasnthralaleuleuasnalasercysalaalametaspgluphe
465470475480
glnleuileprometileserlyscysargthrlysgluglyargarg
485490495
lysthrasnleutyrglypheileilelysglyargserhisleuarg
500505510
asnaspthraspvalvalasnphevalsermetglupheserleuthr
515520525
aspproargphegluprohislystrpglulystyrcysvalleuglu
530535540
ileglyaspmetleuleuargthralavalglyglnvalserargpro
545550555560
metpheleutyrvalargthrasnglythrserlysilelysmetlys
565570575
trpglymetglumetargargcysleuleuglnserleuglnglnile
580585590
glusermetileglualagluserservallysglulysaspmetthr
595600605
lysgluphephegluasnlyssergluthrtrpproileglygluser
610615620
prolysglyvalglugluglyserileglylysvalcysargthrleu
625630635640
leualalysservalpheasnserleutyralaserproglnleuglu
645650655
glypheseralagluserarglysleuleuleuilevalglnalaleu
660665670
lysaspaspleugluproglythrpheaspileglyglyleutyrglu
675680685
serilegluglucysleuileasnaspprotrpvalleuleuasnala
690695700
sertrppheasnserpheleuthrhisalaleulys
705710715
<210>7
<211>838
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(657)
<400>7
atggattccaacactgtgtcaagctttcaggtagactgttttctttgg48
metaspserasnthrvalserserpheglnvalaspcyspheleutrp
151015
catgtccgcaaacgattcgcagaccaagaactgggtgatgccccattc96
hisvalarglysargphealaaspglngluleuglyaspalaprophe
202530
cttgaccggcttcgccgagaccagaagtccctaaggggaagaggtagc144
leuaspargleuargargaspglnlysserleuargglyargglyser
354045
actcttggtctggacatcgaaacagccactcatgcaggaaagcagata192
thrleuglyleuaspilegluthralathrhisalaglylysglnile
505560
gtggagcagattctggaaaaggaatcagatgaggcacttaaaatgacc240
valgluglnileleuglulysgluseraspglualaleulysmetthr
65707580
attgcctctgttcctacttcactctacttaactgacatgactcttgat288
ilealaservalprothrserleutyrleuthraspmetthrleuasp
859095
gagatgtcaagagactggttcatgctcatgcccaagcaaaaagtaaca336
glumetserargasptrpphemetleumetprolysglnlysvalthr
100105110
ggctccctatgtataagaatggaccaggcaatcatggataagaacatc384
glyserleucysileargmetaspglnalailemetasplysasnile
115120125
atacttaaagcaaactttagtgtgattttcgaagggctggaaacacta432
ileleulysalaasnpheservalilephegluglyleugluthrleu
130135140
atactacttagagccttcaccgaagaaggagcagtcgttggcgaaatt480
ileleuleuargalaphethrglugluglyalavalvalglygluile
145150155160
tcaccattaccttctcttccaggacatactaatgaggatgtcaaaaat528
serproleuproserleuproglyhisthrasngluaspvallysasn
165170175
gcaattggggtcctcatcggaggacttaaatggaatgataatacggtt576
alaileglyvalleuileglyglyleulystrpasnaspasnthrval
180185190
agaatctctgaaactctacagagattcgcttggagaagcagtcatgag624
argilesergluthrleuglnargphealatrpargserserhisglu
195200205
aatgggagaccttcattcccttcaaagcagaaatgaaaaatggagagaacaat677
asnglyargproserpheproserlysglnlys
210215
taagccagaaatttgaagaaataagatggttgattgaagaagtgcgacatagattgaaaa737
atacagaaaatagttttgaacaaataacatttatgcaagccttacaactattgcttgaag797
tagaacaagagataagaactttctcgtttcagcttatttaa838
<210>8
<211>219
<212>prt
<213>流感病毒
<400>8
metaspserasnthrvalserserpheglnvalaspcyspheleutrp
151015
hisvalarglysargphealaaspglngluleuglyaspalaprophe
202530
leuaspargleuargargaspglnlysserleuargglyargglyser
354045
thrleuglyleuaspilegluthralathrhisalaglylysglnile
505560
valgluglnileleuglulysgluseraspglualaleulysmetthr
65707580
ilealaservalprothrserleutyrleuthraspmetthrleuasp
859095
glumetserargasptrpphemetleumetprolysglnlysvalthr
100105110
glyserleucysileargmetaspglnalailemetasplysasnile
115120125
ileleulysalaasnpheservalilephegluglyleugluthrleu
130135140
ileleuleuargalaphethrglugluglyalavalvalglygluile
145150155160
serproleuproserleuproglyhisthrasngluaspvallysasn
165170175
alaileglyvalleuileglyglyleulystrpasnaspasnthrval
180185190
argilesergluthrleuglnargphealatrpargserserhisglu
195200205
asnglyargproserpheproserlysglnlys
210215
<210>9
<211>1497
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(1497)
<400>9
atggcgtctcaaggcaccaaacgatcctatgaacagatggaaactgat48
metalaserglnglythrlysargsertyrgluglnmetgluthrasp
151015
ggggaacgccagaatgcaactgaaatcagagcatctgtcggaaggatg96
glygluargglnasnalathrgluileargalaservalglyargmet
202530
gtgggaggaatcggccgattttatgttcagatgtgtactgagcttaaa144
valglyglyileglyargphetyrvalglnmetcysthrgluleulys
354045
ctaaacgaccatgaagggcggctgattcagaacagcataacaatagaa192
leuasnasphisgluglyargleuileglnasnserilethrileglu
505560
aggatggtactttcggcattcgacgaaagaagaaacaagtatctcgag240
argmetvalleuseralapheaspgluargargasnlystyrleuglu
65707580
gagcatcccagtgctgggaaagaccctaagaaaacgggaggcccgata288
gluhisproseralaglylysaspprolyslysthrglyglyproile
859095
tacagaaggaaagatgggaaatggatgagggaactcatcctccatgat336
tyrargarglysaspglylystrpmetarggluleuileleuhisasp
100105110
aaagaagaaatcatgagaatctggcgtcaggccaacaatggtgaagac384
lysglugluilemetargiletrpargglnalaasnasnglygluasp
115120125
gctactgctggtcttactcatatgatgatctggcactccaatctcaat432
alathralaglyleuthrhismetmetiletrphisserasnleuasn
130135140
gacaccacataccaaagaacaagggctcttgttcggactgggatggat480
aspthrthrtyrglnargthrargalaleuvalargthrglymetasp
145150155160
cccagaatgtgctctctgatgcaaggctcaaccctcccacggagatct528
proargmetcysserleumetglnglyserthrleuproargargser
165170175
ggagccgctggtgctgcagtaaaaggtgttggaacaatggtaatggaa576
glyalaalaglyalaalavallysglyvalglythrmetvalmetglu
180185190
ctcatcagaatgatcaaacgcggaataaatgatcggaatttctggaga624
leuileargmetilelysargglyileasnaspargasnphetrparg
195200205
ggtgaaaatggtcgaaaaaccagaattgcttatgaaagaatgtgcaat672
glygluasnglyarglysthrargilealatyrgluargmetcysasn
210215220
atcctcaaagggaaatttcagacagcagcacaacgggctatgatggac720
ileleulysglylyspheglnthralaalaglnargalametmetasp
225230235240
caggtgagggaaggccgcaatcctggaaacgctgagattgaggatctc768
glnvalarggluglyargasnproglyasnalagluilegluaspleu
245250255
attttcttggcacgatcagcacttattttgagaggatcagtagcccat816
ilepheleualaargseralaleuileleuargglyservalalahis
260265270
aaatcatgcctacctgcctgtgtttatggccttgcaataaccagtggg864
lyssercysleuproalacysvaltyrglyleualailethrsergly
275280285
tatgactttgagaaggaaggatactctctggttggaattgatcctttc912
tyrasppheglulysgluglytyrserleuvalglyileaspprophe
290295300
aaactactccagaacagtcaaattttcagtctaatcagaccaaaagaa960
lysleuleuglnasnserglnilepheserleuileargprolysglu
305310315320
aacccagcacacaagagccagttggtgtggatggcatgccattctgca1008
asnproalahislysserglnleuvaltrpmetalacyshisserala
325330335
gcatttgaggacctgagagttttaaatttcattagaggaaccaaagta1056
alaphegluaspleuargvalleuasnpheileargglythrlysval
340345350
atcccaagaggacagttaacaaccagaggagttcaaattgcttcaaat1104
ileproargglyglnleuthrthrargglyvalglnilealaserasn
355360365
gaaaacatggagacaataaattctagcacacttgaactgagaagcaaa1152
gluasnmetgluthrileasnserserthrleugluleuargserlys
370375380
tattgggcaataaggaccagaagcggaggaaacaccagtcaacagaga1200
tyrtrpalaileargthrargserglyglyasnthrserglnglnarg
385390395400
gcatctgcaggacagataagtgtgcaacctactttctcagtacagaga1248
alaseralaglyglnileservalglnprothrpheservalglnarg
405410415
aatctaccctttgagagagcgaccattatggctgcattcactggtaac1296
asnleuprophegluargalathrilemetalaalaphethrglyasn
420425430
actgaagggaggacttccgacatgagaacggaaatcataaggatgatg1344
thrgluglyargthrseraspmetargthrgluileileargmetmet
435440445
gaaaatgccaaatcagaagatgtgtctttccaggggcggggagtcttc1392
gluasnalalyssergluaspvalserpheglnglyargglyvalphe
450455460
gagctctcggacgaaaaggcaacgaacccgatcgtgccttcctttgac1440
gluleuseraspglulysalathrasnproilevalproserpheasp
465470475480
atgagcaatgaagggtcttatttcttcggagacaatgctgaggagttt1488
metserasngluglysertyrphepheglyaspasnalaglugluphe
485490495
gacagttaa1497
aspser
<210>10
<211>498
<212>prt
<213>流感病毒
<400>10
metalaserglnglythrlysargsertyrgluglnmetgluthrasp
151015
glygluargglnasnalathrgluileargalaservalglyargmet
202530
valglyglyileglyargphetyrvalglnmetcysthrgluleulys
354045
leuasnasphisgluglyargleuileglnasnserilethrileglu
505560
argmetvalleuseralapheaspgluargargasnlystyrleuglu
65707580
gluhisproseralaglylysaspprolyslysthrglyglyproile
859095
tyrargarglysaspglylystrpmetarggluleuileleuhisasp
100105110
lysglugluilemetargiletrpargglnalaasnasnglygluasp
115120125
alathralaglyleuthrhismetmetiletrphisserasnleuasn
130135140
aspthrthrtyrglnargthrargalaleuvalargthrglymetasp
145150155160
proargmetcysserleumetglnglyserthrleuproargargser
165170175
glyalaalaglyalaalavallysglyvalglythrmetvalmetglu
180185190
leuileargmetilelysargglyileasnaspargasnphetrparg
195200205
glygluasnglyarglysthrargilealatyrgluargmetcysasn
210215220
ileleulysglylyspheglnthralaalaglnargalametmetasp
225230235240
glnvalarggluglyargasnproglyasnalagluilegluaspleu
245250255
ilepheleualaargseralaleuileleuargglyservalalahis
260265270
lyssercysleuproalacysvaltyrglyleualailethrsergly
275280285
tyrasppheglulysgluglytyrserleuvalglyileaspprophe
290295300
lysleuleuglnasnserglnilepheserleuileargprolysglu
305310315320
asnproalahislysserglnleuvaltrpmetalacyshisserala
325330335
alaphegluaspleuargvalleuasnpheileargglythrlysval
340345350
ileproargglyglnleuthrthrargglyvalglnilealaserasn
355360365
gluasnmetgluthrileasnserserthrleugluleuargserlys
370375380
tyrtrpalaileargthrargserglyglyasnthrserglnglnarg
385390395400
alaseralaglyglnileservalglnprothrpheservalglnarg
405410415
asnleuprophegluargalathrilemetalaalaphethrglyasn
420425430
thrgluglyargthrseraspmetargthrgluileileargmetmet
435440445
gluasnalalyssergluaspvalserpheglnglyargglyvalphe
450455460
gluleuseraspglulysalathrasnproilevalproserpheasp
465470475480
metserasngluglysertyrphepheglyaspasnalaglugluphe
485490495
aspser
<210>11
<211>1413
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(1413)
<400>11
atgaatccaaatcaaaagataatagcaattggatttgcatcattgggg48
metasnproasnglnlysileilealaileglyphealaserleugly
151015
atattaatcattaatgtcattctccatgtagtcagcattatagtaaca96
ileleuileileasnvalileleuhisvalvalserileilevalthr
202530
gtactggtcctcaataacaatagaacagatctgaactgcaaagggacg144
valleuvalleuasnasnasnargthraspleuasncyslysglythr
354045
atcataagaaagtacaatgaaacagtaagagtagaaaaaattactcaa192
ileilearglystyrasngluthrvalargvalglulysilethrgln
505560
tggtataataccagtacaattaagtacatagagagaccttcaaatgaa240
trptyrasnthrserthrilelystyrilegluargproserasnglu
65707580
tactacatgaacaacactgaaccactttgtgaggcccaaggctttgca288
tyrtyrmetasnasnthrgluproleucysglualaglnglypheala
859095
ccattttccaaagataatggaatacgaattgggtcgagaggccatgtt336
propheserlysaspasnglyileargileglyserargglyhisval
100105110
tttgtgataagagaaccttttgtatcatgttcgccctcagaatgtaga384
phevalilearggluprophevalsercysserproserglucysarg
115120125
acctttttcctcacacagggctcattactcaatgacaaacattctaac432
thrphepheleuthrglnglyserleuleuasnasplyshisserasn
130135140
ggcacagtaaaggaccgaagtccgtataggactttgatgagtgtcaaa480
glythrvallysaspargserprotyrargthrleumetservallys
145150155160
atagggcaatcacctaatgtatatcaagctagatttgaatcggtagca528
ileglyglnserproasnvaltyrglnalaargphegluservalala
165170175
tggtcagcaacagcatgccatgatggaaaaaaatggatgacagttgga576
trpseralathralacyshisaspglylyslystrpmetthrvalgly
180185190
gtcacagggcccgacaatcaagcaattgcagtagtgaactatggaggt624
valthrglyproaspasnglnalailealavalvalasntyrglygly
195200205
gttccggttgatattattaattcatgggcaggggatattttaagaacc672
valprovalaspileileasnsertrpalaglyaspileleuargthr
210215220
caagaatcatcatgcacctgcattaaaggagactgttattgggtaatg720
glnglusersercysthrcysilelysglyaspcystyrtrpvalmet
225230235240
actgatggaccggcaaataggcaagctaaatataggatattcaaagca768
thraspglyproalaasnargglnalalystyrargilephelysala
245250255
aaagatggaagagtaattggacagactgatataagtttcaatggggga816
lysaspglyargvalileglyglnthraspileserpheasnglygly
260265270
cacatagaggagtgttcttgttaccccaatgaagggaaggtggaatgc864
hisilegluglucyssercystyrproasngluglylysvalglucys
275280285
atatgcagggacaattggactggaacaaatagaccagttctggtaata912
ilecysargaspasntrpthrglythrasnargprovalleuvalile
290295300
tcttctgatctatcgtacacagttggatatttgtgtgctggcattccc960
serseraspleusertyrthrvalglytyrleucysalaglyilepro
305310315320
actgacactcctaggggagaggatagtcaattcacaggctcatgtaca1008
thraspthrproargglygluaspserglnphethrglysercysthr
325330335
agtcctttgggaaataaaggatacggtgtaaaaggtttcgggtttcga1056
serproleuglyasnlysglytyrglyvallysglypheglyphearg
340345350
caaggaactgacgtatgggccggaaggacaattagtaggacttcaaga1104
glnglythraspvaltrpalaglyargthrileserargthrserarg
355360365
tcaggattcgaaataataaaaatcaggaatggttggacacagaacagt1152
serglyphegluileilelysileargasnglytrpthrglnasnser
370375380
aaagaccaaatcaggaggcaagtgattatcgatgacccaaattggtca1200
lysaspglnileargargglnvalileileaspaspproasntrpser
385390395400
ggatatagcggttctttcacattgccggttgaactaacaaaaaaggga1248
glytyrserglyserphethrleuprovalgluleuthrlyslysgly
405410415
tgtttggtcccctgtttctgggttgaaatgattagaggtaaacctgaa1296
cysleuvalprocysphetrpvalglumetileargglylysproglu
420425430
gaaacaacaatatggacctctagtagctccattgtgatgtgtggagta1344
gluthrthriletrpthrserserserserilevalmetcysglyval
435440445
gatcataaaattgccagttggtcatggcacgatggagctattcttccc1392
asphislysilealasertrpsertrphisaspglyalaileleupro
450455460
tttgacatcgataagatgtaa1413
pheaspileasplysmet
465470
<210>12
<211>470
<212>prt
<213>流感病毒
<400>12
metasnproasnglnlysileilealaileglyphealaserleugly
151015
ileleuileileasnvalileleuhisvalvalserileilevalthr
202530
valleuvalleuasnasnasnargthraspleuasncyslysglythr
354045
ileilearglystyrasngluthrvalargvalglulysilethrgln
505560
trptyrasnthrserthrilelystyrilegluargproserasnglu
65707580
tyrtyrmetasnasnthrgluproleucysglualaglnglypheala
859095
propheserlysaspasnglyileargileglyserargglyhisval
100105110
phevalilearggluprophevalsercysserproserglucysarg
115120125
thrphepheleuthrglnglyserleuleuasnasplyshisserasn
130135140
glythrvallysaspargserprotyrargthrleumetservallys
145150155160
ileglyglnserproasnvaltyrglnalaargphegluservalala
165170175
trpseralathralacyshisaspglylyslystrpmetthrvalgly
180185190
valthrglyproaspasnglnalailealavalvalasntyrglygly
195200205
valprovalaspileileasnsertrpalaglyaspileleuargthr
210215220
glnglusersercysthrcysilelysglyaspcystyrtrpvalmet
225230235240
thraspglyproalaasnargglnalalystyrargilephelysala
245250255
lysaspglyargvalileglyglnthraspileserpheasnglygly
260265270
hisilegluglucyssercystyrproasngluglylysvalglucys
275280285
ilecysargaspasntrpthrglythrasnargprovalleuvalile
290295300
serseraspleusertyrthrvalglytyrleucysalaglyilepro
305310315320
thraspthrproargglygluaspserglnphethrglysercysthr
325330335
serproleuglyasnlysglytyrglyvallysglypheglyphearg
340345350
glnglythraspvaltrpalaglyargthrileserargthrserarg
355360365
serglyphegluileilelysileargasnglytrpthrglnasnser
370375380
lysaspglnileargargglnvalileileaspaspproasntrpser
385390395400
glytyrserglyserphethrleuprovalgluleuthrlyslysgly
405410415
cysleuvalprocysphetrpvalglumetileargglylysproglu
420425430
gluthrthriletrpthrserserserserilevalmetcysglyval
435440445
asphislysilealasertrpsertrphisaspglyalaileleupro
450455460
pheaspileasplysmet
465470
<210>13
<211>982
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(756)
<400>13
atgagtcttctaaccgaggtcgaaacgtacgttctctctatcgtacca48
metserleuleuthrgluvalgluthrtyrvalleuserilevalpro
151015
tcaggccccctcaaagccgagatcgcgcagagacttgaagatgtcttt96
serglyproleulysalagluilealaglnargleugluaspvalphe
202530
gcaggaaagaacaccgatcttgaggcactcatggaatggctaaagaca144
alaglylysasnthraspleuglualaleumetglutrpleulysthr
354045
agaccaatcctgtcacctctgactaaagggattttaggatttgtattc192
argproileleuserproleuthrlysglyileleuglyphevalphe
505560
acgctcaccgtgcccagtgagcgaggactgcagcgtagacgctttgtc240
thrleuthrvalprosergluargglyleuglnargargargpheval
65707580
caaaatgcccttagtggaaacggagatccaaacaacatggacagagca288
glnasnalaleuserglyasnglyaspproasnasnmetaspargala
859095
gtaaaactgtacaggaagcttaaaagagaaataacattccatggggca336
vallysleutyrarglysleulysarggluilethrphehisglyala
100105110
aaagaggtagcactcagctattccactggtgcactagccagctgcatg384
lysgluvalalaleusertyrserthrglyalaleualasercysmet
115120125
ggactcatatacaacagaatgggaactgttacaaccgaagtggcattt432
glyleuiletyrasnargmetglythrvalthrthrgluvalalaphe
130135140
ggcctggtatgcgccacatgtgaacagattgctgattcccagcatcga480
glyleuvalcysalathrcysgluglnilealaaspserglnhisarg
145150155160
gctcacaggcagatggtgacaacaaccaacccattgatcagacatgaa528
alahisargglnmetvalthrthrthrasnproleuilearghisglu
165170175
aacagaatggtattagccagtaccacggctaaagccatggaacagatg576
asnargmetvalleualaserthrthralalysalametgluglnmet
180185190
gcaggatcgagtgagcaggcagcagaggccatggaggttgctagtagg624
alaglysersergluglnalaalaglualametgluvalalaserarg
195200205
gctaggcagatggtacaggcaatgagaaccattgggacccaccctagc672
alaargglnmetvalglnalametargthrileglythrhisproser
210215220
tccagtgccggtttgaaagatgatctccttgaaaatttacaggcctac720
serseralaglyleulysaspaspleuleugluasnleuglnalatyr
225230235240
cagaaacggatgggagtgcaaatgcagcgattcaagtgatcctctc766
glnlysargmetglyvalglnmetglnargphelys
245250
gttattgcagcaagtatcattgggatcttgcacttgatattgtggattcttgatcgtctt826
ttcttcaaattcatttatcgtcgccttaaatacgggttgaaaagagggccttctacggaa886
ggagtacctgagtctatgagggaagaatatcggcaggaacagcagaatgctgtggatgtt946
gacgatggtcattttgtcaacatagagctggagtaa982
<210>14
<211>252
<212>prt
<213>流感病毒
<400>14
metserleuleuthrgluvalgluthrtyrvalleuserilevalpro
151015
serglyproleulysalagluilealaglnargleugluaspvalphe
202530
alaglylysasnthraspleuglualaleumetglutrpleulysthr
354045
argproileleuserproleuthrlysglyileleuglyphevalphe
505560
thrleuthrvalprosergluargglyleuglnargargargpheval
65707580
glnasnalaleuserglyasnglyaspproasnasnmetaspargala
859095
vallysleutyrarglysleulysarggluilethrphehisglyala
100105110
lysgluvalalaleusertyrserthrglyalaleualasercysmet
115120125
glyleuiletyrasnargmetglythrvalthrthrgluvalalaphe
130135140
glyleuvalcysalathrcysgluglnilealaaspserglnhisarg
145150155160
alahisargglnmetvalthrthrthrasnproleuilearghisglu
165170175
asnargmetvalleualaserthrthralalysalametgluglnmet
180185190
alaglysersergluglnalaalaglualametgluvalalaserarg
195200205
alaargglnmetvalglnalametargthrileglythrhisproser
210215220
serseralaglyleulysaspaspleuleugluasnleuglnalatyr
225230235240
glnlysargmetglyvalglnmetglnargphelys
245250
<210>15
<211>1698
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(1698)
<400>15
atgaagacaaccattattttgatactactaacccattgggcctacagt48
metlysthrthrileileleuileleuleuthrhistrpalatyrser
151015
caaaacccaatcagtggcaacaacacagccacactgtgtctgggacac96
glnasnproileserglyasnasnthralathrleucysleuglyhis
202530
catgcagtagcaaatggaacattggtaaaaacaatgagtgatgatcaa144
hisalavalalaasnglythrleuvallysthrmetseraspaspgln
354045
attgaggtgacaaatgctacagaattagttcagagcatttcaatgggg192
ilegluvalthrasnalathrgluleuvalglnserilesermetgly
505560
aaaatatgcaacaaatcatatagaattctagatggaagaaattgcaca240
lysilecysasnlyssertyrargileleuaspglyargasncysthr
65707580
ttaatagatgcaatgctaggagacccccactgtgacgcctttcagtat288
leuileaspalametleuglyaspprohiscysaspalapheglntyr
859095
gagagttgggacctcttcatagaaagaagcaacgctttcagcaattgc336
glusertrpaspleupheilegluargserasnalapheserasncys
100105110
tacccatatgacatccctgactatgcatcgctccgatccattgtagca384
tyrprotyraspileproasptyralaserleuargserilevalala
115120125
tcctcaggaacattggaattcacagcagagggattcacatggacaggt432
serserglythrleugluphethralagluglyphethrtrpthrgly
130135140
gtcactcaaaacggaagaagtggagcctgcaaaaggggatcagccgat480
valthrglnasnglyargserglyalacyslysargglyseralaasp
145150155160
agtttctttagccgactgaattggctaacaaaatctggaagctcttac528
serphepheserargleuasntrpleuthrlysserglysersertyr
165170175
cccacattgaatgtgacaatgcctaacaataaaaatttcgacaagcta576
prothrleuasnvalthrmetproasnasnlysasnpheasplysleu
180185190
tacatctgggggattcatcacccgagctcaaatcaagagcagacaaaa624
tyriletrpglyilehishisproserserasnglngluglnthrlys
195200205
ttgtacatccaagaatcaggacgagtaacagtctcaacaaaaagaagt672
leutyrileglngluserglyargvalthrvalserthrlysargser
210215220
caacaaacaataatccctaacatcggatctagaccgttggtcagaggt720
glnglnthrileileproasnileglyserargproleuvalarggly
225230235240
caatcaggcaggataagcatatactggaccattgtaaaacctggagat768
glnserglyargileseriletyrtrpthrilevallysproglyasp
245250255
atcctaatgataaacagtaatggcaacttagttgcaccgcggggatat816
ileleumetileasnserasnglyasnleuvalalaproargglytyr
260265270
tttaaattgaaaacagggaaaagctctgtaatgagatcagatgcaccc864
phelysleulysthrglylysserservalmetargseraspalapro
275280285
atagacatttgtgtgtctgaatgtattacaccaaatggaagcatctcc912
ileaspilecysvalserglucysilethrproasnglyserileser
290295300
aacgacaagccattccaaaatgtgaacaaagttacatatggaaaatgc960
asnasplyspropheglnasnvalasnlysvalthrtyrglylyscys
305310315320
cctaagtatatcaggcaaaacactttaaagctggccactgggatgagg1008
prolystyrileargglnasnthrleulysleualathrglymetarg
325330335
aatgtaccagaaaagcaaaccagaggaatctttggagcaatagcggga1056
asnvalproglulysglnthrargglyilepheglyalailealagly
340345350
ttcatcgaaaacggctgggaaggaatggttgatgggtggtatgggttc1104
pheilegluasnglytrpgluglymetvalaspglytrptyrglyphe
355360365
cgatatcaaaactctgaaggaacagggcaagctgcagatctaaagagc1152
argtyrglnasnsergluglythrglyglnalaalaaspleulysser
370375380
actcaagcagccatcgaccagattaatggaaagttaaacagagtgatt1200
thrglnalaalaileaspglnileasnglylysleuasnargvalile
385390395400
gaaagaaccaatgagaaattccatcaaatagagaaggaattctcagaa1248
gluargthrasnglulysphehisglnileglulysglupheserglu
405410415
gtagaaggaagaattcaggacctggagaaatatgtagaagacaccaaa1296
valgluglyargileglnaspleuglulystyrvalgluaspthrlys
420425430
atagacctatggtcctacaatgcagaattgctggtggctctagaaaat1344
ileaspleutrpsertyrasnalagluleuleuvalalaleugluasn
435440445
caacatacaattgacttaacagatgcagaaatgaataaattatttgag1392
glnhisthrileaspleuthraspalaglumetasnlysleupheglu
450455460
aagactagacgccagttaagagaaaacgcagaagacatgggaggtgga1440
lysthrargargglnleuarggluasnalagluaspmetglyglygly
465470475480
tgtttcaagatttaccacaaatgtgataatgcatgcattggatcaata1488
cysphelysiletyrhislyscysaspasnalacysileglyserile
485490495
agaactgggacatatgaccattacatatacagagatgaagcattaaac1536
argthrglythrtyrasphistyriletyrargaspglualaleuasn
500505510
aaccgatttcagatcaaaggtgtagagttgaaatcaggctacaaagat1584
asnargpheglnilelysglyvalgluleulysserglytyrlysasp
515520525
tggatattgtggatttcattcgccatatcatgcttcttaatttgcgtt1632
trpileleutrpileserphealailesercyspheleuilecysval
530535540
gttctattgggtttcattatgtgggcttgccaaagaggcaacatcaga1680
valleuleuglypheilemettrpalacysglnargglyasnilearg
545550555560
tgcaacatttgcatttga1698
cysasnilecysile
565
<210>16
<211>565
<212>prt
<213>流感病毒
<400>16
metlysthrthrileileleuileleuleuthrhistrpalatyrser
151015
glnasnproileserglyasnasnthralathrleucysleuglyhis
202530
hisalavalalaasnglythrleuvallysthrmetseraspaspgln
354045
ilegluvalthrasnalathrgluleuvalglnserilesermetgly
505560
lysilecysasnlyssertyrargileleuaspglyargasncysthr
65707580
leuileaspalametleuglyaspprohiscysaspalapheglntyr
859095
glusertrpaspleupheilegluargserasnalapheserasncys
100105110
tyrprotyraspileproasptyralaserleuargserilevalala
115120125
serserglythrleugluphethralagluglyphethrtrpthrgly
130135140
valthrglnasnglyargserglyalacyslysargglyseralaasp
145150155160
serphepheserargleuasntrpleuthrlysserglysersertyr
165170175
prothrleuasnvalthrmetproasnasnlysasnpheasplysleu
180185190
tyriletrpglyilehishisproserserasnglngluglnthrlys
195200205
leutyrileglngluserglyargvalthrvalserthrlysargser
210215220
glnglnthrileileproasnileglyserargproleuvalarggly
225230235240
glnserglyargileseriletyrtrpthrilevallysproglyasp
245250255
ileleumetileasnserasnglyasnleuvalalaproargglytyr
260265270
phelysleulysthrglylysserservalmetargseraspalapro
275280285
ileaspilecysvalserglucysilethrproasnglyserileser
290295300
asnasplyspropheglnasnvalasnlysvalthrtyrglylyscys
305310315320
prolystyrileargglnasnthrleulysleualathrglymetarg
325330335
asnvalproglulysglnthrargglyilepheglyalailealagly
340345350
pheilegluasnglytrpgluglymetvalaspglytrptyrglyphe
355360365
argtyrglnasnsergluglythrglyglnalaalaaspleulysser
370375380
thrglnalaalaileaspglnileasnglylysleuasnargvalile
385390395400
gluargthrasnglulysphehisglnileglulysglupheserglu
405410415
valgluglyargileglnaspleuglulystyrvalgluaspthrlys
420425430
ileaspleutrpsertyrasnalagluleuleuvalalaleugluasn
435440445
glnhisthrileaspleuthraspalaglumetasnlysleupheglu
450455460
lysthrargargglnleuarggluasnalagluaspmetglyglygly
465470475480
cysphelysiletyrhislyscysaspasnalacysileglyserile
485490495
argthrglythrtyrasphistyriletyrargaspglualaleuasn
500505510
asnargpheglnilelysglyvalgluleulysserglytyrlysasp
515520525
trpileleutrpileserphealailesercyspheleuilecysval
530535540
valleuleuglypheilemettrpalacysglnargglyasnilearg
545550555560
cysasnilecysile
565
<210>17
<211>2277
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(2277)
<400>17
atggagagaataaaagaactgagagatctgatgttacaatcccgcacc48
metgluargilelysgluleuargaspleumetleuglnserargthr
151015
cgcgagatactaacaaaaactactgtggaccacatggccataatcaag96
arggluileleuthrlysthrthrvalasphismetalaileilelys
202530
aaatacacatcaggaagacaagagaagaaccctgcacttaggatgaaa144
lystyrthrserglyargglnglulysasnproalaleuargmetlys
354045
tggatgatggcaatgaaatacccaattacagcagataagaggataatg192
trpmetmetalametlystyrproilethralaasplysargilemet
505560
gagatgattcctgagagaaatgaacagggacaaaccctttggagcaaa240
glumetileprogluargasngluglnglyglnthrleutrpserlys
65707580
acgaacgatgctggctcagaccgcgtaatggtatcacctctggcagtg288
thrasnaspalaglyseraspargvalmetvalserproleualaval
859095
acatggtggaataggaatggaccaacaacgagcacaattcattatcca336
thrtrptrpasnargasnglyprothrthrserthrilehistyrpro
100105110
aaagtctacaaaacttattttgaaaaggttgaaagattgaaacacgga384
lysvaltyrlysthrtyrpheglulysvalgluargleulyshisgly
115120125
acctttggccccgttcattttaggaatcaagtcaagataagacgaaga432
thrpheglyprovalhispheargasnglnvallysileargargarg
130135140
gttgatgtaaaccctggtcacgcggacctcagtgccaaagaagcacaa480
valaspvalasnproglyhisalaaspleuseralalysglualagln
145150155160
gatgtgatcatggaagttgttttcccaaatgaagtgggagccagaatt528
aspvalilemetgluvalvalpheproasngluvalglyalaargile
165170175
ctaacatcggaatcacaactaacaataaccaaagagaaaaaggaagaa576
leuthrsergluserglnleuthrilethrlysglulyslysgluglu
180185190
cttcaggactgcaaaattgctcccttgatggtagcatacatgctagaa624
leuglnaspcyslysilealaproleumetvalalatyrmetleuglu
195200205
agagagttggtccgaaaaacaaggttcctcccagtagcaggcggaaca672
arggluleuvalarglysthrargpheleuprovalalaglyglythr
210215220
agcagtgtatacattgaagtgttgcatctgactcagggaacatgctgg720
serservaltyrilegluvalleuhisleuthrglnglythrcystrp
225230235240
gagcaaatgtacaccccaggaggagaagttagaaacgatgatattgat768
gluglnmettyrthrproglyglygluvalargasnaspaspileasp
245250255
caaagtttaattattgcagcccggaacatagtgagaagagcgacagta816
glnserleuileilealaalaargasnilevalargargalathrval
260265270
tcagcagatccactagcatccctactggaaatgtgccacagtacacag864
seralaaspproleualaserleuleuglumetcyshisserthrgln
275280285
attggtggaataaggatggtagacatccttaagcagaatccaacagag912
ileglyglyileargmetvalaspileleulysglnasnprothrglu
290295300
gaacaagctgtggatatatgcaaagcagcaatgggattgagaattagc960
gluglnalavalaspilecyslysalaalametglyleuargileser
305310315320
tcatcattcagctttggtggattcaccttcaaaagaacaagtggatca1008
serserpheserpheglyglyphethrphelysargthrserglyser
325330335
tcagtcaagagagaagaagaaatgcttacgggcaaccttcaaacattg1056
servallysargglugluglumetleuthrglyasnleuglnthrleu
340345350
aaaataagagtgcatgagggctatgaagaattcacaatggtcggaaga1104
lysileargvalhisgluglytyrglugluphethrmetvalglyarg
355360365
agagcaacagccattatcagaaaggcaaccagaagattgattcaattg1152
argalathralaileilearglysalathrargargleuileglnleu
370375380
atagtaagtgggagagatgaacaatcaattgctgaagcaataattgta1200
ilevalserglyargaspgluglnserilealaglualaileileval
385390395400
gccatggtgttttcgcaagaagattgcatgataaaagcagttcgaggc1248
alametvalpheserglngluaspcysmetilelysalavalarggly
405410415
gatttgaactttgttaatagagcaaatcagcgtttgaaccccatgcat1296
aspleuasnphevalasnargalaasnglnargleuasnpromethis
420425430
caactcttgaggcatttccaaaaagatgcaaaagtgcttttccaaaat1344
glnleuleuarghispheglnlysaspalalysvalleupheglnasn
435440445
tggggaattgaacccatcgacaatgtaatggggatgattggaatattg1392
trpglyilegluproileaspasnvalmetglymetileglyileleu
450455460
cctgacatgaccccaagcaccgagatgtcattgagaggagtgagagtc1440
proaspmetthrproserthrglumetserleuargglyvalargval
465470475480
agcaaaatgggagtggatgagtactccagcactgagagagtggtggtg1488
serlysmetglyvalaspglutyrserserthrgluargvalvalval
485490495
agcattgaccgttttttaagagttcgggatcaaaggggaaacatacta1536
serileaspargpheleuargvalargaspglnargglyasnileleu
500505510
ctgtcccctgaagaagtcagtgaaacacaaggaacggaaaagctgaca1584
leuserproglugluvalsergluthrglnglythrglulysleuthr
515520525
ataatttattcgtcatcaatgatgtgggagattaatggtcccgaatca1632
ileiletyrsersersermetmettrpgluileasnglyprogluser
530535540
gtgttggtcaatacttatcaatggatcatcaggaactgggaaattgta1680
valleuvalasnthrtyrglntrpileileargasntrpgluileval
545550555560
aaaattcagtggtcacaggaccccacaatgttatacaataagatagaa1728
lysileglntrpserglnaspprothrmetleutyrasnlysileglu
565570575
tttgagccattccaatccctggtccctagggccaccagaagccaatac1776
pheglupropheglnserleuvalproargalathrargserglntyr
580585590
agcggtttcgtaagaaccctgtttcagcaaatgcgagatgtacttgga1824
serglyphevalargthrleupheglnglnmetargaspvalleugly
595600605
acatttgatactgctcaaataataaaactcctcccttttgccgctgct1872
thrpheaspthralaglnileilelysleuleuprophealaalaala
610615620
cctccggaacagagtaggatgcagttctcttctttgactgttaatgta1920
proprogluglnserargmetglnpheserserleuthrvalasnval
625630635640
agaggttcgggaatgaggatacttgtaagaggcaattccccagtgttc1968
argglyserglymetargileleuvalargglyasnserprovalphe
645650655
aactacaataaagccactaaaaggctcacagtcctcggaaaggatgca2016
asntyrasnlysalathrlysargleuthrvalleuglylysaspala
660665670
ggtgcgcttactgaggacccagatgaaggtacggctggagtagaatct2064
glyalaleuthrgluaspproaspgluglythralaglyvalgluser
675680685
gctgttctaagagggtttctcattttaggtaaagaaaacaagagatat2112
alavalleuargglypheleuileleuglylysgluasnlysargtyr
690695700
ggcccagcactaagcatcaatgaactaagcaaacttgcaaaaggggag2160
glyproalaleuserileasngluleuserlysleualalysglyglu
705710715720
aaagccaatgtactaattgggcaaggggacrtagtgttggtaatgaaa2208
lysalaasnvalleuileglyglnglyaspxaavalleuvalmetlys
725730735
cggaaacgtgactctagcatacttactgacagccagacagcgaccaaa2256
arglysargaspserserileleuthraspserglnthralathrlys
740745750
aggattcggatggccatcaat2277
argileargmetalaileasn
755
<210>18
<211>759
<212>prt
<213>流感病毒
<220>
<221>misc_feature
<222>(731)..(731)
<223>731位的’xaa’代表val或者ile。
<400>18
metgluargilelysgluleuargaspleumetleuglnserargthr
151015
arggluileleuthrlysthrthrvalasphismetalaileilelys
202530
lystyrthrserglyargglnglulysasnproalaleuargmetlys
354045
trpmetmetalametlystyrproilethralaasplysargilemet
505560
glumetileprogluargasngluglnglyglnthrleutrpserlys
65707580
thrasnaspalaglyseraspargvalmetvalserproleualaval
859095
thrtrptrpasnargasnglyprothrthrserthrilehistyrpro
100105110
lysvaltyrlysthrtyrpheglulysvalgluargleulyshisgly
115120125
thrpheglyprovalhispheargasnglnvallysileargargarg
130135140
valaspvalasnproglyhisalaaspleuseralalysglualagln
145150155160
aspvalilemetgluvalvalpheproasngluvalglyalaargile
165170175
leuthrsergluserglnleuthrilethrlysglulyslysgluglu
180185190
leuglnaspcyslysilealaproleumetvalalatyrmetleuglu
195200205
arggluleuvalarglysthrargpheleuprovalalaglyglythr
210215220
serservaltyrilegluvalleuhisleuthrglnglythrcystrp
225230235240
gluglnmettyrthrproglyglygluvalargasnaspaspileasp
245250255
glnserleuileilealaalaargasnilevalargargalathrval
260265270
seralaaspproleualaserleuleuglumetcyshisserthrgln
275280285
ileglyglyileargmetvalaspileleulysglnasnprothrglu
290295300
gluglnalavalaspilecyslysalaalametglyleuargileser
305310315320
serserpheserpheglyglyphethrphelysargthrserglyser
325330335
servallysargglugluglumetleuthrglyasnleuglnthrleu
340345350
lysileargvalhisgluglytyrglugluphethrmetvalglyarg
355360365
argalathralaileilearglysalathrargargleuileglnleu
370375380
ilevalserglyargaspgluglnserilealaglualaileileval
385390395400
alametvalpheserglngluaspcysmetilelysalavalarggly
405410415
aspleuasnphevalasnargalaasnglnargleuasnpromethis
420425430
glnleuleuarghispheglnlysaspalalysvalleupheglnasn
435440445
trpglyilegluproileaspasnvalmetglymetileglyileleu
450455460
proaspmetthrproserthrglumetserleuargglyvalargval
465470475480
serlysmetglyvalaspglutyrserserthrgluargvalvalval
485490495
serileaspargpheleuargvalargaspglnargglyasnileleu
500505510
leuserproglugluvalsergluthrglnglythrglulysleuthr
515520525
ileiletyrsersersermetmettrpgluileasnglyprogluser
530535540
valleuvalasnthrtyrglntrpileileargasntrpgluileval
545550555560
lysileglntrpserglnaspprothrmetleutyrasnlysileglu
565570575
pheglupropheglnserleuvalproargalathrargserglntyr
580585590
serglyphevalargthrleupheglnglnmetargaspvalleugly
595600605
thrpheaspthralaglnileilelysleuleuprophealaalaala
610615620
proprogluglnserargmetglnpheserserleuthrvalasnval
625630635640
argglyserglymetargileleuvalargglyasnserprovalphe
645650655
asntyrasnlysalathrlysargleuthrvalleuglylysaspala
660665670
glyalaleuthrgluaspproaspgluglythralaglyvalgluser
675680685
alavalleuargglypheleuileleuglylysgluasnlysargtyr
690695700
glyproalaleuserileasngluleuserlysleualalysglyglu
705710715720
lysalaasnvalleuileglyglnglyaspxaavalleuvalmetlys
725730735
arglysargaspserserileleuthraspserglnthralathrlys
740745750
argileargmetalaileasn
755
<210>19
<211>2274
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(2274)
<400>19
atggatgtcaatccgactctacttttcttaaaggtgccagcgcaaaat48
metaspvalasnprothrleuleupheleulysvalproalaglnasn
151015
gctataagcacaacattcccttatactggagatcctccctacagtcat96
alaileserthrthrpheprotyrthrglyaspproprotyrserhis
202530
ggaacagggacaggatacaccatggatactgtcaacagaacacaccaa144
glythrglythrglytyrthrmetaspthrvalasnargthrhisgln
354045
tattcagaaaaagggaaatggacaacaaacactgagattggagcacca192
tyrserglulysglylystrpthrthrasnthrgluileglyalapro
505560
caacttaatccaatcgatggaccacttcctgaagacaatgaaccaagt240
glnleuasnproileaspglyproleuprogluaspasngluproser
65707580
gggtacgcccaaacagattgtgtattggaagcaatggctttccttgaa288
glytyralaglnthraspcysvalleuglualametalapheleuglu
859095
gaatcccatcccggaatctttgaaaattcgtgtcttgaaacgatggag336
gluserhisproglyilephegluasnsercysleugluthrmetglu
100105110
gtgattcagcagacaagagtggacaaactaacacaaggccgacaaact384
valileglnglnthrargvalasplysleuthrglnglyargglnthr
115120125
tatgattggaccttgaataggaatcaacctgccgcaacagcacttgct432
tyrasptrpthrleuasnargasnglnproalaalathralaleuala
130135140
aatacgattgaagtattcagatcaaatggtctgacttccaatgaatcg480
asnthrilegluvalpheargserasnglyleuthrserasngluser
145150155160
gggagattgatggacttcctcaaagatgtcatggagtccatgaacaag528
glyargleumetasppheleulysaspvalmetglusermetasnlys
165170175
gaagaaatggaaataacaacacacttccaacggaagagaagagtaaga576
gluglumetgluilethrthrhispheglnarglysargargvalarg
180185190
gacaacatgacaaagagaatggtaacacagagaaccatagggaagaaa624
aspasnmetthrlysargmetvalthrglnargthrileglylyslys
195200205
aaacaacgattaaacagaaagagctatctaatcagaacattaacccta672
lysglnargleuasnarglyssertyrleuileargthrleuthrleu
210215220
aacacaatgaccaaggacgctgagagagggaaattgaaacgacgagca720
asnthrmetthrlysaspalagluargglylysleulysargargala
225230235240
atcgctaccccagggatgcagataagagggtttgtatattttgttgaa768
ilealathrproglymetglnileargglyphevaltyrphevalglu
245250255
acactagcccgaagaatatgtgaaaagcttgaacaatcaggattgcca816
thrleualaargargilecysglulysleugluglnserglyleupro
260265270
gttggcggtaatgagaaaaaggccaaactggctaatgtcgtcagaaaa864
valglyglyasnglulyslysalalysleualaasnvalvalarglys
275280285
atgatgactaattcccaagacactgaactctccttcaccatcactggg912
metmetthrasnserglnaspthrgluleuserphethrilethrgly
290295300
gacaataccaaatggaatgaaaatcagaacccacgcatattcctggca960
aspasnthrlystrpasngluasnglnasnproargilepheleuala
305310315320
atgatcacatacataactagaaaccagccagaatggttcagaaatgtt1008
metilethrtyrilethrargasnglnproglutrppheargasnval
325330335
ctaagcattgcaccgattatgttctcaaataaaatggcaagactgggg1056
leuserilealaproilemetpheserasnlysmetalaargleugly
340345350
aaaggatatatgtttgaaagcaaaagtatgaaattgagaactcaaata1104
lysglytyrmetphegluserlyssermetlysleuargthrglnile
355360365
ccagcagaaatgctagcaagcattgacctaaaatatttcaatgattca1152
proalaglumetleualaserileaspleulystyrpheasnaspser
370375380
acaaaaaagaaaattgaaaagatacgaccacttctggttgacgggact1200
thrlyslyslysileglulysileargproleuleuvalaspglythr
385390395400
gcttcactgagtcctggcatgatgatgggaatgttcaacatgttgagc1248
alaserleuserproglymetmetmetglymetpheasnmetleuser
405410415
actgtgctgggtgtatccatattaaacctgggccagaggaaatacaca1296
thrvalleuglyvalserileleuasnleuglyglnarglystyrthr
420425430
aagaccacatactggtgggatggtctgcaatcatccgatgactttgct1344
lysthrthrtyrtrptrpaspglyleuglnserseraspasppheala
435440445
ttgatagtgaatgcgcctaatcatgaaggaatacaagctggagtagac1392
leuilevalasnalaproasnhisgluglyileglnalaglyvalasp
450455460
agattctatagaacttgcaaactggtcgggatcaacatgagcaaaaag1440
argphetyrargthrcyslysleuvalglyileasnmetserlyslys
465470475480
aaatcctacataaatagaactggaacattcgaattcacaagctttttc1488
lyssertyrileasnargthrglythrphegluphethrserphephe
485490495
taccggtatggttttgtagccaatttcagcatggaactacccagtttt1536
tyrargtyrglyphevalalaasnphesermetgluleuproserphe
500505510
ggggtttccggaataaatgaatctgcagacatgagcattggagtgaca1584
glyvalserglyileasngluseralaaspmetserileglyvalthr
515520525
gtcatcaaaaacaacatgataaataatgatctcggtcctgccacggca1632
valilelysasnasnmetileasnasnaspleuglyproalathrala
530535540
caaatggcactccaactcttcattaaggattatcggtacacataccgg1680
glnmetalaleuglnleupheilelysasptyrargtyrthrtyrarg
545550555560
tgccatagaggtgatacccagatacaaaccagaagatcttttgagttg1728
cyshisargglyaspthrglnileglnthrargargserphegluleu
565570575
aagaaactgtgggaacagactcgatcaaagactggtctactggtatca1776
lyslysleutrpgluglnthrargserlysthrglyleuleuvalser
580585590
gatgggggtccaaacctatataacatcagaaacctacacatcccggaa1824
aspglyglyproasnleutyrasnileargasnleuhisileproglu
595600605
gtctgtttaaaatgggagctaatggatgaagattataaggggaggcta1872
valcysleulystrpgluleumetaspgluasptyrlysglyargleu
610615620
tgcaatccattgaatcctttcgttagtcacaaagaaattgaatcagtc1920
cysasnproleuasnprophevalserhislysgluilegluserval
625630635640
aacagtgcagtagtaatgcctgcgcatggccctgccaaaagcatggag1968
asnseralavalvalmetproalahisglyproalalyssermetglu
645650655
tatgatgctgttgcaacaacacattcttggatccccaagaggaaccgg2016
tyraspalavalalathrthrhissertrpileprolysargasnarg
660665670
tccatattgaacacaagccaaaggggaatactcgaagatgagcagatg2064
serileleuasnthrserglnargglyileleugluaspgluglnmet
675680685
tatcagaaatgctgcaacctgtttgaaaaattcttccccagcagctca2112
tyrglnlyscyscysasnleupheglulysphepheproserserser
690695700
tacagaagaccagtcggaatttctagtatggttgaggccatggtgtcc2160
tyrargargprovalglyilesersermetvalglualametvalser
705710715720
agggcccgcattgatgcacgaattgacttcgaatctggacggataaag2208
argalaargileaspalaargileaspphegluserglyargilelys
725730735
aaggatgagttcgctgagatcatgaagatctgttccaccattgaagag2256
lysaspgluphealagluilemetlysilecysserthrilegluglu
740745750
ctcagacggcaaaaatag2274
leuargargglnlys
755
<210>20
<211>757
<212>prt
<213>流感病毒
<400>20
metaspvalasnprothrleuleupheleulysvalproalaglnasn
151015
alaileserthrthrpheprotyrthrglyaspproprotyrserhis
202530
glythrglythrglytyrthrmetaspthrvalasnargthrhisgln
354045
tyrserglulysglylystrpthrthrasnthrgluileglyalapro
505560
glnleuasnproileaspglyproleuprogluaspasngluproser
65707580
glytyralaglnthraspcysvalleuglualametalapheleuglu
859095
gluserhisproglyilephegluasnsercysleugluthrmetglu
100105110
valileglnglnthrargvalasplysleuthrglnglyargglnthr
115120125
tyrasptrpthrleuasnargasnglnproalaalathralaleuala
130135140
asnthrilegluvalpheargserasnglyleuthrserasngluser
145150155160
glyargleumetasppheleulysaspvalmetglusermetasnlys
165170175
gluglumetgluilethrthrhispheglnarglysargargvalarg
180185190
aspasnmetthrlysargmetvalthrglnargthrileglylyslys
195200205
lysglnargleuasnarglyssertyrleuileargthrleuthrleu
210215220
asnthrmetthrlysaspalagluargglylysleulysargargala
225230235240
ilealathrproglymetglnileargglyphevaltyrphevalglu
245250255
thrleualaargargilecysglulysleugluglnserglyleupro
260265270
valglyglyasnglulyslysalalysleualaasnvalvalarglys
275280285
metmetthrasnserglnaspthrgluleuserphethrilethrgly
290295300
aspasnthrlystrpasngluasnglnasnproargilepheleuala
305310315320
metilethrtyrilethrargasnglnproglutrppheargasnval
325330335
leuserilealaproilemetpheserasnlysmetalaargleugly
340345350
lysglytyrmetphegluserlyssermetlysleuargthrglnile
355360365
proalaglumetleualaserileaspleulystyrpheasnaspser
370375380
thrlyslyslysileglulysileargproleuleuvalaspglythr
385390395400
alaserleuserproglymetmetmetglymetpheasnmetleuser
405410415
thrvalleuglyvalserileleuasnleuglyglnarglystyrthr
420425430
lysthrthrtyrtrptrpaspglyleuglnserseraspasppheala
435440445
leuilevalasnalaproasnhisgluglyileglnalaglyvalasp
450455460
argphetyrargthrcyslysleuvalglyileasnmetserlyslys
465470475480
lyssertyrileasnargthrglythrphegluphethrserphephe
485490495
tyrargtyrglyphevalalaasnphesermetgluleuproserphe
500505510
glyvalserglyileasngluseralaaspmetserileglyvalthr
515520525
valilelysasnasnmetileasnasnaspleuglyproalathrala
530535540
glnmetalaleuglnleupheilelysasptyrargtyrthrtyrarg
545550555560
cyshisargglyaspthrglnileglnthrargargserphegluleu
565570575
lyslysleutrpgluglnthrargserlysthrglyleuleuvalser
580585590
aspglyglyproasnleutyrasnileargasnleuhisileproglu
595600605
valcysleulystrpgluleumetaspgluasptyrlysglyargleu
610615620
cysasnproleuasnprophevalserhislysgluilegluserval
625630635640
asnseralavalvalmetproalahisglyproalalyssermetglu
645650655
tyraspalavalalathrthrhissertrpileprolysargasnarg
660665670
serileleuasnthrserglnargglyileleugluaspgluglnmet
675680685
tyrglnlyscyscysasnleupheglulysphepheproserserser
690695700
tyrargargprovalglyilesersermetvalglualametvalser
705710715720
argalaargileaspalaargileaspphegluserglyargilelys
725730735
lysaspgluphealagluilemetlysilecysserthrilegluglu
740745750
leuargargglnlys
755
<210>21
<211>2151
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(2151)
<400>21
atggaagactttgtgcgacagtgcttcaatccaatgatcgtcgagctt48
metgluaspphevalargglncyspheasnprometilevalgluleu
151015
gcggaaaaggcaatgaaagaatatggagagaacccgaaaatcgaaaca96
alaglulysalametlysglutyrglygluasnprolysilegluthr
202530
aacaaatttgcagcaatatgcactcacttggaagtctgcttcatgtac144
asnlysphealaalailecysthrhisleugluvalcysphemettyr
354045
tcggattttcactttattaatgaactgggtgagtcagtggtcatagag192
seraspphehispheileasngluleuglygluservalvalileglu
505560
tctggtgacccaaatgctcttttgaaacacagatttgaaatcattgag240
serglyaspproasnalaleuleulyshisargphegluileileglu
65707580
gggagagatcgaacaatggcatggacagtagtaaacagcatctgcaac288
glyargaspargthrmetalatrpthrvalvalasnserilecysasn
859095
accacaagagctgaaaaacctaaatttcttccagatttatacgactat336
thrthrargalaglulysprolyspheleuproaspleutyrasptyr
100105110
aaggagaacagatttgttgaaattggtgtgacaaggagagaagttcac384
lysgluasnargphevalgluileglyvalthrargarggluvalhis
115120125
atatactacctggagaaggccaacaaaataaagtctgagaaaacacat432
iletyrtyrleuglulysalaasnlysilelysserglulysthrhis
130135140
atccacattttctcatttacaggagaggaaatggctacaaaagcggac480
ilehisilepheserphethrglygluglumetalathrlysalaasp
145150155160
tatactcttgatgaagagagtagagccaggatcaagaccagactattc528
tyrthrleuaspglugluserargalaargilelysthrargleuphe
165170175
actataagacaagaaatggccagtagaggcctctgggattcctttcgt576
thrileargglnglumetalaserargglyleutrpaspserphearg
180185190
cagtccgagagaggcgaagagacaattgaagaaagatttgaaatcaca624
glnsergluargglyglugluthrileglugluargphegluilethr
195200205
gggacgatgcgcaagcttgccaattacagtctcccaccgaacttctcc672
glythrmetarglysleualaasntyrserleuproproasnpheser
210215220
agccttgaaaattttagagtctatgtggatggattcgaaccgaacggc720
serleugluasnpheargvaltyrvalaspglyphegluproasngly
225230235240
tgcattgagagtaagctttctcaaatgtccaaagaagtaaatgccaga768
cysilegluserlysleuserglnmetserlysgluvalasnalaarg
245250255
atcgaaccattttcaaagacaacaccccgaccactcaaaatgccaggt816
ileglupropheserlysthrthrproargproleulysmetprogly
260265270
ggtccaccctgccatcagcgatctaaattcttgctaatggatgctctg864
glyproprocyshisglnargserlyspheleuleumetaspalaleu
275280285
aaactgagcattgaggacccaagtcacgagggagagggaataccacta912
lysleuserilegluaspproserhisgluglygluglyileproleu
290295300
tatgatgcaatcaaatgcatgaaaactttctttggatggaaagagccc960
tyraspalailelyscysmetlysthrphepheglytrplysglupro
305310315320
agtattgttaaaccacatgaaaagggtataaacccgaactatctccaa1008
serilevallysprohisglulysglyileasnproasntyrleugln
325330335
acttggaagcaagtattagaagaaatacaagaccttgagaacgaagaa1056
thrtrplysglnvalleuglugluileglnaspleugluasngluglu
340345350
aggacccccaagaccaagaatatgaaaaaaacaagccaattgaaatgg1104
argthrprolysthrlysasnmetlyslysthrserglnleulystrp
355360365
gcactaggtgaaaatatggcaccagagaaagtggattttgaggattgt1152
alaleuglygluasnmetalaproglulysvalaspphegluaspcys
370375380
aaagacatcaatgatttaaaacaatatgacagtgatgagccagaaaca1200
lysaspileasnaspleulysglntyraspseraspgluprogluthr
385390395400
aggtctcttgcaagttggattcaaagtgagttcaacaaagcttgtgag1248
argserleualasertrpileglnserglupheasnlysalacysglu
405410415
ctgacagattcaagctggatagagctcgatgaaattggggaggatgtc1296
leuthraspsersertrpilegluleuaspgluileglygluaspval
420425430
gccccaatagaatacattgcgagcatgaggagaaattattttactgct1344
alaproileglutyrilealasermetargargasntyrphethrala
435440445
gagatttcccattgtagagcaacagaatatataatgaaaggagtgtac1392
gluileserhiscysargalathrglutyrilemetlysglyvaltyr
450455460
atcaacactgctctactcaatgcatcctgtgctgcgatggatgaattt1440
ileasnthralaleuleuasnalasercysalaalametaspgluphe
465470475480
caattaattccgatgataagtaaatgcaggaccaaagaagggagaagg1488
glnleuileprometileserlyscysargthrlysgluglyargarg
485490495
aaaacaaatttatatggattcataataaagggaaggtcccatttaaga1536
lysthrasnleutyrglypheileilelysglyargserhisleuarg
500505510
aatgatactgacgtggtgaactttgtaagtatggaattttctctcact1584
asnaspthraspvalvalasnphevalsermetglupheserleuthr
515520525
gatccaagatttgagccacacaaatgggaaaaatactgcgttctagaa1632
aspproargphegluprohislystrpglulystyrcysvalleuglu
530535540
attggagacatgcttctaagaactgctgtaggtcaagtgtcaagaccc1680
ileglyaspmetleuleuargthralavalglyglnvalserargpro
545550555560
atgtttttgtatgtaaggacaaatggaacctctaaaattaaaatgaaa1728
metpheleutyrvalargthrasnglythrserlysilelysmetlys
565570575
tggggaatggaaatgaggcgctgcctccttcagtctctgcaacagatt1776
trpglymetglumetargargcysleuleuglnserleuglnglnile
580585590
gaaagcatgatcgaagctgagtcctcagtcaaagaaaaggacatgacc1824
glusermetileglualagluserservallysglulysaspmetthr
595600605
aaagaattttttgagaacaaatcagagacatggcctataggagagtcc1872
lysgluphephegluasnlyssergluthrtrpproileglygluser
610615620
cccaaaggagtggaagagggctcaatcgggaaggtttgcaggacctta1920
prolysglyvalglugluglyserileglylysvalcysargthrleu
625630635640
ttagcaaaatctgtgtttaacagtttatatgcatctccacaactggaa1968
leualalysservalpheasnserleutyralaserproglnleuglu
645650655
gggttttcagctgaatctaggaaattacttctcattgttcaggctctt2016
glypheseralagluserarglysleuleuleuilevalglnalaleu
660665670
agggatgacctggaacctggaacctttgatattggggggttatatgaa2064
argaspaspleugluproglythrpheaspileglyglyleutyrglu
675680685
tcaattgaggagtgcctgattaatgatccctgggttttgcttaatgca2112
serilegluglucysleuileasnaspprotrpvalleuleuasnala
690695700
tcttggttcaactccttccttacacatgcactgaagtag2151
sertrppheasnserpheleuthrhisalaleulys
705710715
<210>22
<211>716
<212>prt
<213>流感病毒
<400>22
metgluaspphevalargglncyspheasnprometilevalgluleu
151015
alaglulysalametlysglutyrglygluasnprolysilegluthr
202530
asnlysphealaalailecysthrhisleugluvalcysphemettyr
354045
seraspphehispheileasngluleuglygluservalvalileglu
505560
serglyaspproasnalaleuleulyshisargphegluileileglu
65707580
glyargaspargthrmetalatrpthrvalvalasnserilecysasn
859095
thrthrargalaglulysprolyspheleuproaspleutyrasptyr
100105110
lysgluasnargphevalgluileglyvalthrargarggluvalhis
115120125
iletyrtyrleuglulysalaasnlysilelysserglulysthrhis
130135140
ilehisilepheserphethrglygluglumetalathrlysalaasp
145150155160
tyrthrleuaspglugluserargalaargilelysthrargleuphe
165170175
thrileargglnglumetalaserargglyleutrpaspserphearg
180185190
glnsergluargglyglugluthrileglugluargphegluilethr
195200205
glythrmetarglysleualaasntyrserleuproproasnpheser
210215220
serleugluasnpheargvaltyrvalaspglyphegluproasngly
225230235240
cysilegluserlysleuserglnmetserlysgluvalasnalaarg
245250255
ileglupropheserlysthrthrproargproleulysmetprogly
260265270
glyproprocyshisglnargserlyspheleuleumetaspalaleu
275280285
lysleuserilegluaspproserhisgluglygluglyileproleu
290295300
tyraspalailelyscysmetlysthrphepheglytrplysglupro
305310315320
serilevallysprohisglulysglyileasnproasntyrleugln
325330335
thrtrplysglnvalleuglugluileglnaspleugluasngluglu
340345350
argthrprolysthrlysasnmetlyslysthrserglnleulystrp
355360365
alaleuglygluasnmetalaproglulysvalaspphegluaspcys
370375380
lysaspileasnaspleulysglntyraspseraspgluprogluthr
385390395400
argserleualasertrpileglnserglupheasnlysalacysglu
405410415
leuthraspsersertrpilegluleuaspgluileglygluaspval
420425430
alaproileglutyrilealasermetargargasntyrphethrala
435440445
gluileserhiscysargalathrglutyrilemetlysglyvaltyr
450455460
ileasnthralaleuleuasnalasercysalaalametaspgluphe
465470475480
glnleuileprometileserlyscysargthrlysgluglyargarg
485490495
lysthrasnleutyrglypheileilelysglyargserhisleuarg
500505510
asnaspthraspvalvalasnphevalsermetglupheserleuthr
515520525
aspproargphegluprohislystrpglulystyrcysvalleuglu
530535540
ileglyaspmetleuleuargthralavalglyglnvalserargpro
545550555560
metpheleutyrvalargthrasnglythrserlysilelysmetlys
565570575
trpglymetglumetargargcysleuleuglnserleuglnglnile
580585590
glusermetileglualagluserservallysglulysaspmetthr
595600605
lysgluphephegluasnlyssergluthrtrpproileglygluser
610615620
prolysglyvalglugluglyserileglylysvalcysargthrleu
625630635640
leualalysservalpheasnserleutyralaserproglnleuglu
645650655
glypheseralagluserarglysleuleuleuilevalglnalaleu
660665670
argaspaspleugluproglythrpheaspileglyglyleutyrglu
675680685
serilegluglucysleuileasnaspprotrpvalleuleuasnala
690695700
sertrppheasnserpheleuthrhisalaleulys
705710715
<210>23
<211>838
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(657)
<400>23
atggattccaacactgtgtcaagctttcaggtagactgttttctttgg48
metaspserasnthrvalserserpheglnvalaspcyspheleutrp
151015
catgtccgcaaacgattcgcagaccaagaactgggtgatgccccattc96
hisvalarglysargphealaaspglngluleuglyaspalaprophe
202530
cttgaccggcttcgccgagaccagaagtccctaaggggaagaggtagc144
leuaspargleuargargaspglnlysserleuargglyargglyser
354045
actcttggtctggacatcgaaacagccactcatgcaggaaagcagata192
thrleuglyleuaspilegluthralathrhisalaglylysglnile
505560
gtggagcagattctggaaaaggaatcagatgaggcacttaaaatgacc240
valgluglnileleuglulysgluseraspglualaleulysmetthr
65707580
attgcctctgttcctacttcacgctacttaactgacatgactcttgat288
ilealaservalprothrserargtyrleuthraspmetthrleuasp
859095
gagatgtcaagagactggttcatgctcatgcccaagcaaaaagtaaca336
glumetserargasptrpphemetleumetprolysglnlysvalthr
100105110
ggctccctatgtataagaatggaccaggcaatcatggataagaacatc384
glyserleucysileargmetaspglnalailemetasplysasnile
115120125
atacttaaagcaaactttagtgtgattttcgaagggctggaaacacta432
ileleulysalaasnpheservalilephegluglyleugluthrleu
130135140
atactacttagagccttcaccgaagaaggagcagtcgttggcgaaatt480
ileleuleuargalaphethrglugluglyalavalvalglygluile
145150155160
tcaccattaccttctcttccaggacatactaatgaggatgtcaaaaat528
serproleuproserleuproglyhisthrasngluaspvallysasn
165170175
gcaattggggtcctcatcggaggacttaaatggaatgataatacggtt576
alaileglyvalleuileglyglyleulystrpasnaspasnthrval
180185190
agaatctctgaaactctacagagattcgcttggagaagcagtcatgag624
argilesergluthrleuglnargphealatrpargserserhisglu
195200205
aatgggagaccttcattcccttcaaagcagaaatgaaaaatggagagaacaat677
asnglyargproserpheproserlysglnlys
210215
taagccagaaatttgaagaaataagatggttgattgaagaagtgcgacatagattgaaaa737
atacagaaaatagttttgaacaaataacatttatgcaagccttacaactattgcttgaag797
tagaacaagagataagaactttctcgtttcagcttatttaa838
<210>24
<211>219
<212>prt
<213>流感病毒
<400>24
metaspserasnthrvalserserpheglnvalaspcyspheleutrp
151015
hisvalarglysargphealaaspglngluleuglyaspalaprophe
202530
leuaspargleuargargaspglnlysserleuargglyargglyser
354045
thrleuglyleuaspilegluthralathrhisalaglylysglnile
505560
valgluglnileleuglulysgluseraspglualaleulysmetthr
65707580
ilealaservalprothrserargtyrleuthraspmetthrleuasp
859095
glumetserargasptrpphemetleumetprolysglnlysvalthr
100105110
glyserleucysileargmetaspglnalailemetasplysasnile
115120125
ileleulysalaasnpheservalilephegluglyleugluthrleu
130135140
ileleuleuargalaphethrglugluglyalavalvalglygluile
145150155160
serproleuproserleuproglyhisthrasngluaspvallysasn
165170175
alaileglyvalleuileglyglyleulystrpasnaspasnthrval
180185190
argilesergluthrleuglnargphealatrpargserserhisglu
195200205
asnglyargproserpheproserlysglnlys
210215
<210>25
<211>1497
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(1497)
<400>25
atggcgtctcaaggcaccaaacgatcctatgaacagatggaaactgat48
metalaserglnglythrlysargsertyrgluglnmetgluthrasp
151015
ggggaacgccagaatgcaactgaaatcagagcatctgtcggaaggatg96
glygluargglnasnalathrgluileargalaservalglyargmet
202530
gtgggaggaatcggccggttttatgttcagatgtgtactgagcttaaa144
valglyglyileglyargphetyrvalglnmetcysthrgluleulys
354045
ctaaacgaccatgaagggcggctgattcagaacagcataacaatagaa192
leuasnasphisgluglyargleuileglnasnserilethrileglu
505560
aggatggtactttcggcattcgacgaaagaagaaacaagtatctcgag240
argmetvalleuseralapheaspgluargargasnlystyrleuglu
65707580
gagcatcccagtgctgggaaagaccctaagaaaacgggaggcccgata288
gluhisproseralaglylysaspprolyslysthrglyglyproile
859095
tacagaaggaaagatgggaaatggatgagggaactcatcctccatgat336
tyrargarglysaspglylystrpmetarggluleuileleuhisasp
100105110
aaagaagaaatcatgagaatctggcgtcaggccaacaatggtgaagac384
lysglugluilemetargiletrpargglnalaasnasnglygluasp
115120125
gctactgctggtcttactcatatgatgatctggcactccaatctcaat432
alathralaglyleuthrhismetmetiletrphisserasnleuasn
130135140
gacaccacataccaaagaacaagggctcttgttcggactgggatggat480
aspthrthrtyrglnargthrargalaleuvalargthrglymetasp
145150155160
cccagaatgtgctctctgatgcaaggctcaaccctcccacggagatct528
proargmetcysserleumetglnglyserthrleuproargargser
165170175
ggagccgctggtgctgcagtaaaaggtgttggaacaatggtaatggaa576
glyalaalaglyalaalavallysglyvalglythrmetvalmetglu
180185190
ctcatcagaatgatcaaacgcggaataaatgatcggaatttctggaga624
leuileargmetilelysargglyileasnaspargasnphetrparg
195200205
ggtgaaaatggtcgaagaaccagaattgcttatgaaagaatgtgcaat672
glygluasnglyargargthrargilealatyrgluargmetcysasn
210215220
atcctcaaagggaaatttcagacagcagcacaacgggctatgatggac720
ileleulysglylyspheglnthralaalaglnargalametmetasp
225230235240
caggtgagggaaggccgcaatcctggaaacgctgagattgaggatctc768
glnvalarggluglyargasnproglyasnalagluilegluaspleu
245250255
attttcttggcacgatcagcacttattttgagaggatcagtagcccat816
ilepheleualaargseralaleuileleuargglyservalalahis
260265270
aaatcatgcctacctgcctgtgtttatggccttgcagtaaccagtggg864
lyssercysleuproalacysvaltyrglyleualavalthrsergly
275280285
tatgactttgagaaggaaggatactctctggttggaattgatcctttc912
tyrasppheglulysgluglytyrserleuvalglyileaspprophe
290295300
aaactactccagaacagtcaaattttcagtctaatcagaccaaaagaa960
lysleuleuglnasnserglnilepheserleuileargprolysglu
305310315320
aacccagcacacaagagccagttggtgtggatggcatgccattctgca1008
asnproalahislysserglnleuvaltrpmetalacyshisserala
325330335
gcatttgaggacctgagagttttaaatttcattagaggaaccaaagta1056
alaphegluaspleuargvalleuasnpheileargglythrlysval
340345350
atcccaagaggacagttaacaaccagaggagttcaaattgcttcaaat1104
ileproargglyglnleuthrthrargglyvalglnilealaserasn
355360365
gaaaacatggagacaatagattctagcacacttgaactgagaagcaaa1152
gluasnmetgluthrileaspserserthrleugluleuargserlys
370375380
tattgggcaataaggaccagaagcggaggaaacaccagtcaacagaga1200
tyrtrpalaileargthrargserglyglyasnthrserglnglnarg
385390395400
gcatctgcaggacagataagtgtgcaacctactttctcagtacagaga1248
alaseralaglyglnileservalglnprothrpheservalglnarg
405410415
aatcttccctttgagagagcaaccattatggctgcattcactggtaac1296
asnleuprophegluargalathrilemetalaalaphethrglyasn
420425430
actgaagggaggacttccgacatgagaacggaaatcataaggatgatg1344
thrgluglyargthrseraspmetargthrgluileileargmetmet
435440445
gaaaatgccaaatcagaagatgtgtctttccaggggcggggagtcttc1392
gluasnalalyssergluaspvalserpheglnglyargglyvalphe
450455460
gagctctcggacgaaaaggcaacgaacccgatcgtgccttcctttgac1440
gluleuseraspglulysalathrasnproilevalproserpheasp
465470475480
atgagcaatgaagggtcttatttcttcggagacaatgctgaggagttt1488
metserasngluglysertyrphepheglyaspasnalaglugluphe
485490495
gacagttaa1497
aspser
<210>26
<211>498
<212>prt
<213>流感病毒
<400>26
metalaserglnglythrlysargsertyrgluglnmetgluthrasp
151015
glygluargglnasnalathrgluileargalaservalglyargmet
202530
valglyglyileglyargphetyrvalglnmetcysthrgluleulys
354045
leuasnasphisgluglyargleuileglnasnserilethrileglu
505560
argmetvalleuseralapheaspgluargargasnlystyrleuglu
65707580
gluhisproseralaglylysaspprolyslysthrglyglyproile
859095
tyrargarglysaspglylystrpmetarggluleuileleuhisasp
100105110
lysglugluilemetargiletrpargglnalaasnasnglygluasp
115120125
alathralaglyleuthrhismetmetiletrphisserasnleuasn
130135140
aspthrthrtyrglnargthrargalaleuvalargthrglymetasp
145150155160
proargmetcysserleumetglnglyserthrleuproargargser
165170175
glyalaalaglyalaalavallysglyvalglythrmetvalmetglu
180185190
leuileargmetilelysargglyileasnaspargasnphetrparg
195200205
glygluasnglyargargthrargilealatyrgluargmetcysasn
210215220
ileleulysglylyspheglnthralaalaglnargalametmetasp
225230235240
glnvalarggluglyargasnproglyasnalagluilegluaspleu
245250255
ilepheleualaargseralaleuileleuargglyservalalahis
260265270
lyssercysleuproalacysvaltyrglyleualavalthrsergly
275280285
tyrasppheglulysgluglytyrserleuvalglyileaspprophe
290295300
lysleuleuglnasnserglnilepheserleuileargprolysglu
305310315320
asnproalahislysserglnleuvaltrpmetalacyshisserala
325330335
alaphegluaspleuargvalleuasnpheileargglythrlysval
340345350
ileproargglyglnleuthrthrargglyvalglnilealaserasn
355360365
gluasnmetgluthrileaspserserthrleugluleuargserlys
370375380
tyrtrpalaileargthrargserglyglyasnthrserglnglnarg
385390395400
alaseralaglyglnileservalglnprothrpheservalglnarg
405410415
asnleuprophegluargalathrilemetalaalaphethrglyasn
420425430
thrgluglyargthrseraspmetargthrgluileileargmetmet
435440445
gluasnalalyssergluaspvalserpheglnglyargglyvalphe
450455460
gluleuseraspglulysalathrasnproilevalproserpheasp
465470475480
metserasngluglysertyrphepheglyaspasnalaglugluphe
485490495
aspser
<210>27
<211>1410
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(1410)
<400>27
atgaatccaaatcaaaagataataacaattggatttgcatcattgggg48
metasnproasnglnlysileilethrileglyphealaserleugly
151015
atattaatcattaatgtcattctccatgtagtcagcattatagtaaca96
ileleuileileasnvalileleuhisvalvalserileilevalthr
202530
gtactggtcctcaataacaatagaacagatctgaactgcaaagggacg144
valleuvalleuasnasnasnargthraspleuasncyslysglythr
354045
atcataagagagtacaatgaaacagtaagagtagaaaaaattactcaa192
ileileargglutyrasngluthrvalargvalglulysilethrgln
505560
tggtataataccagtacaattaagtacatagagagaccttcaaatgaa240
trptyrasnthrserthrilelystyrilegluargproserasnglu
65707580
tactacatgaacaacactgaaccactttgtgaggcccaaggctttgca288
tyrtyrmetasnasnthrgluproleucysglualaglnglypheala
859095
ccattttccaaagataatggaatacgaattgggtcgagaggccatgtt336
propheserlysaspasnglyileargileglyserargglyhisval
100105110
tttgtgataagagaaccttttgtatcatgttcgccctcagaatgtaga384
phevalilearggluprophevalsercysserproserglucysarg
115120125
acctttttcctcacacagggctcattactcaatgacaaacattctaac432
thrphepheleuthrglnglyserleuleuasnasplyshisserasn
130135140
ggcacagtaaaggaccgaagtccgtataggactttgatgagtgtcaaa480
glythrvallysaspargserprotyrargthrleumetservallys
145150155160
atagggcaatcacctaatgtatatcaagctaggtttgaatcggtggca528
ileglyglnserproasnvaltyrglnalaargphegluservalala
165170175
tggtcagcaacagcatgccatgatggaaaaaaatggatgacagttgga576
trpseralathralacyshisaspglylyslystrpmetthrvalgly
180185190
gtcacagggcccgacaatcaagcaattgcagtagtgaactatggaggt624
valthrglyproaspasnglnalailealavalvalasntyrglygly
195200205
gttccggttgatattattaattcatgggcaggggatattttaagaacc672
valprovalaspileileasnsertrpalaglyaspileleuargthr
210215220
caagaatcatcatgcacctgcattaaaggagactgttattgggtaatg720
glnglusersercysthrcysilelysglyaspcystyrtrpvalmet
225230235240
actgatggaccggcaaataggcaagctaaatataggatattcaaagca768
thraspglyproalaasnargglnalalystyrargilephelysala
245250255
aaagatggaagagtaattggacagactgatataagtttcaatggggga816
lysaspglyargvalileglyglnthraspileserpheasnglygly
260265270
cacatagaggagtgttcttgttaccccaatgaagggaaggtggaatgc864
hisilegluglucyssercystyrproasngluglylysvalglucys
275280285
atatgcagggacaattggactggaacaaatagaccaattctggtaata912
ilecysargaspasntrpthrglythrasnargproileleuvalile
290295300
tcttctgatctatcgtacacagttggatatttgtgtgctggcattccc960
serseraspleusertyrthrvalglytyrleucysalaglyilepro
305310315320
actgacactcctaggggagaggatagtcaattcacaggctcatgtaca1008
thraspthrproargglygluaspserglnphethrglysercysthr
325330335
agtcctttgggaaataaaggatacggtgtaaaaggtttcgggtttcga1056
serproleuglyasnlysglytyrglyvallysglypheglyphearg
340345350
caaggaactgacgtatgggccggaaggacaattagtaggacttcaaga1104
glnglythraspvaltrpalaglyargthrileserargthrserarg
355360365
tcaggattcgaaataataaaaatcaggaatggttggacacagaacagt1152
serglyphegluileilelysileargasnglytrpthrglnasnser
370375380
aaagaccaaatcaggaggcaagtgattatcgatgacccaaattggtca1200
lysaspglnileargargglnvalileileaspaspproasntrpser
385390395400
ggatatagcggttctttcacattgccggttgaactaacaaaaaaggga1248
glytyrserglyserphethrleuprovalgluleuthrlyslysgly
405410415
tgtttggtcccctgtttctgggttgaaatgattagaggtaaacctgaa1296
cysleuvalprocysphetrpvalglumetileargglylysproglu
420425430
gaaacaacaatatggacctctagcagctccattgtgatgtgtggagta1344
gluthrthriletrpthrserserserserilevalmetcysglyval
435440445
gatcataaaattgccagttggtcatggcacgatggagctattcttccc1392
asphislysilealasertrpsertrphisaspglyalaileleupro
450455460
tttgacatcgataagatg1410
pheaspileasplysmet
465470
<210>28
<211>470
<212>prt
<213>流感病毒
<400>28
metasnproasnglnlysileilethrileglyphealaserleugly
151015
ileleuileileasnvalileleuhisvalvalserileilevalthr
202530
valleuvalleuasnasnasnargthraspleuasncyslysglythr
354045
ileileargglutyrasngluthrvalargvalglulysilethrgln
505560
trptyrasnthrserthrilelystyrilegluargproserasnglu
65707580
tyrtyrmetasnasnthrgluproleucysglualaglnglypheala
859095
propheserlysaspasnglyileargileglyserargglyhisval
100105110
phevalilearggluprophevalsercysserproserglucysarg
115120125
thrphepheleuthrglnglyserleuleuasnasplyshisserasn
130135140
glythrvallysaspargserprotyrargthrleumetservallys
145150155160
ileglyglnserproasnvaltyrglnalaargphegluservalala
165170175
trpseralathralacyshisaspglylyslystrpmetthrvalgly
180185190
valthrglyproaspasnglnalailealavalvalasntyrglygly
195200205
valprovalaspileileasnsertrpalaglyaspileleuargthr
210215220
glnglusersercysthrcysilelysglyaspcystyrtrpvalmet
225230235240
thraspglyproalaasnargglnalalystyrargilephelysala
245250255
lysaspglyargvalileglyglnthraspileserpheasnglygly
260265270
hisilegluglucyssercystyrproasngluglylysvalglucys
275280285
ilecysargaspasntrpthrglythrasnargproileleuvalile
290295300
serseraspleusertyrthrvalglytyrleucysalaglyilepro
305310315320
thraspthrproargglygluaspserglnphethrglysercysthr
325330335
serproleuglyasnlysglytyrglyvallysglypheglyphearg
340345350
glnglythraspvaltrpalaglyargthrileserargthrserarg
355360365
serglyphegluileilelysileargasnglytrpthrglnasnser
370375380
lysaspglnileargargglnvalileileaspaspproasntrpser
385390395400
glytyrserglyserphethrleuprovalgluleuthrlyslysgly
405410415
cysleuvalprocysphetrpvalglumetileargglylysproglu
420425430
gluthrthriletrpthrserserserserilevalmetcysglyval
435440445
asphislysilealasertrpsertrphisaspglyalaileleupro
450455460
pheaspileasplysmet
465470
<210>29
<211>982
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(756)
<400>29
atgagtcttctaaccgaggtcgaaacgtacgttctctctatcgtacca48
metserleuleuthrgluvalgluthrtyrvalleuserilevalpro
151015
tcaggccccctcaaagccgagatcgcgcagagacttgaagatgtcttt96
serglyproleulysalagluilealaglnargleugluaspvalphe
202530
gcagggaagaacaccgatcttgaggcactcatggaatggctaaagaca144
alaglylysasnthraspleuglualaleumetglutrpleulysthr
354045
agaccaatcctgtcacctctgactaaagggattttaggatttgtattc192
argproileleuserproleuthrlysglyileleuglyphevalphe
505560
acgctcaccgtgcccagtgagcgaggactgcagcgtagacgctttgtc240
thrleuthrvalprosergluargglyleuglnargargargpheval
65707580
caaaatgcccttagtggaaacggagatccaaacaacatggacagagca288
glnasnalaleuserglyasnglyaspproasnasnmetaspargala
859095
gtaaaactgtacaggaagcttaaaagagaaataacattccatggggca336
vallysleutyrarglysleulysarggluilethrphehisglyala
100105110
aaagaggtggcactcagctattccactggtgcactagccagctgcatg384
lysgluvalalaleusertyrserthrglyalaleualasercysmet
115120125
ggactcatatacaacagaatgggaactgttacaaccgaagtggcattt432
glyleuiletyrasnargmetglythrvalthrthrgluvalalaphe
130135140
ggcctggtatgcgccacatgtgaacagattgctgattcccagcatcga480
glyleuvalcysalathrcysgluglnilealaaspserglnhisarg
145150155160
tctcacaggcagatggtgacaacaaccaacccattaatcagacatgaa528
serhisargglnmetvalthrthrthrasnproleuilearghisglu
165170175
aacagaatggtattagccagtaccacggctaaagccatggaacagatg576
asnargmetvalleualaserthrthralalysalametgluglnmet
180185190
gcaggatcgagtgagcaggcagcagaggccatggaggttgctagtagg624
alaglysersergluglnalaalaglualametgluvalalaserarg
195200205
gctaggcagatggtacaggcaatgagaaccattgggacccaccctagc672
alaargglnmetvalglnalametargthrileglythrhisproser
210215220
tccagtgccggtttgaaagatgatctccttgaaaatttacaggcctac720
serseralaglyleulysaspaspleuleugluasnleuglnalatyr
225230235240
cagaaacggatgggagtgcaaatgcagcgattcaagtgatcctctc766
glnlysargmetglyvalglnmetglnargphelys
245250
gttattgcagcaagtatcattgggatcttgcacttgatattgtggattcttgatcgtctt826
ttcttcaaattcatttatcgtcgccttaaatacgggttgaaaagagggccttctacggaa886
ggagtacctgagtctatgagggaagaatatcggcaggaacagcagaatgctgtggatgtt946
gacgatggtcattttgtcaacatagagctggagtaa982
<210>30
<211>252
<212>prt
<213>流感病毒
<400>30
metserleuleuthrgluvalgluthrtyrvalleuserilevalpro
151015
serglyproleulysalagluilealaglnargleugluaspvalphe
202530
alaglylysasnthraspleuglualaleumetglutrpleulysthr
354045
argproileleuserproleuthrlysglyileleuglyphevalphe
505560
thrleuthrvalprosergluargglyleuglnargargargpheval
65707580
glnasnalaleuserglyasnglyaspproasnasnmetaspargala
859095
vallysleutyrarglysleulysarggluilethrphehisglyala
100105110
lysgluvalalaleusertyrserthrglyalaleualasercysmet
115120125
glyleuiletyrasnargmetglythrvalthrthrgluvalalaphe
130135140
glyleuvalcysalathrcysgluglnilealaaspserglnhisarg
145150155160
serhisargglnmetvalthrthrthrasnproleuilearghisglu
165170175
asnargmetvalleualaserthrthralalysalametgluglnmet
180185190
alaglysersergluglnalaalaglualametgluvalalaserarg
195200205
alaargglnmetvalglnalametargthrileglythrhisproser
210215220
serseralaglyleulysaspaspleuleugluasnleuglnalatyr
225230235240
glnlysargmetglyvalglnmetglnargphelys
245250
<210>31
<211>1698
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(1698)
<400>31
atgaagacaaccattattttgatactactgacccattgggcctacagt48
metlysthrthrileileleuileleuleuthrhistrpalatyrser
151015
caaaacccaatcagtgacaacaacacagccacactgtgtctgggacac96
glnasnproileseraspasnasnthralathrleucysleuglyhis
202530
catgcagtagcaaatggaacattggtaaaaacaataagtgatgatcaa144
hisalavalalaasnglythrleuvallysthrileseraspaspgln
354045
attgaggtgacaaatgctacagaattagttcagagcatttcaatgggg192
ilegluvalthrasnalathrgluleuvalglnserilesermetgly
505560
aaaatatgcaacaaatcatatagaattctagatggaagaaattgcaca240
lysilecysasnlyssertyrargileleuaspglyargasncysthr
65707580
ttaatagatgcaatgctaggagacccccactgtgacgcctttcagtat288
leuileaspalametleuglyaspprohiscysaspalapheglntyr
859095
gagagttgggacctctttatagaaagaagcagcgctttcagcaattgc336
glusertrpaspleupheilegluargserseralapheserasncys
100105110
tacccatatgacatccctgactatgcatcgctccgatccattgtagca384
tyrprotyraspileproasptyralaserleuargserilevalala
115120125
tcctcaggaacattggaattcacagcagagggattcacatggacaggt432
serserglythrleugluphethralagluglyphethrtrpthrgly
130135140
gtcactcaaaacggaagaagtggagcctgcaaaaggggatcagccgat480
valthrglnasnglyargserglyalacyslysargglyseralaasp
145150155160
agtttctttagccgactgaattggctaacaaaatctggaagctcttac528
serphepheserargleuasntrpleuthrlysserglysersertyr
165170175
cccacattgaatgtgacaatgcctaacaataaaaatttcgacaagcta576
prothrleuasnvalthrmetproasnasnlysasnpheasplysleu
180185190
tacatctgggggattcatcacccgagctcaaatcaagagcagacaaaa624
tyriletrpglyilehishisproserserasnglngluglnthrlys
195200205
ttgtacatccaagaatcaggacgagtaacagtctcaacaaaaagaagt672
leutyrileglngluserglyargvalthrvalserthrlysargser
210215220
caacaaacaataatccctaacatcggatctagaccgttggtcagaggt720
glnglnthrileileproasnileglyserargproleuvalarggly
225230235240
caatcaggcaggataagcatatactggaccattgtaaaacctggagat768
glnserglyargileseriletyrtrpthrilevallysproglyasp
245250255
atcctaatgataaacagtaatggcaacttagttgcaccgcggggatat816
ileleumetileasnserasnglyasnleuvalalaproargglytyr
260265270
tttaaattgaaaacagggaaaagctctgtaatgagatcagatgtaccc864
phelysleulysthrglylysserservalmetargseraspvalpro
275280285
atagacatttgtgtgtctgaatgtattacaccaaatggaagcatctcc912
ileaspilecysvalserglucysilethrproasnglyserileser
290295300
aacgacaagccattccaaaatgtgaacaaagttacatatggaaaatgc960
asnasplyspropheglnasnvalasnlysvalthrtyrglylyscys
305310315320
cccaagtatatcaggcaaaacactttaaagctggccactgggatgagg1008
prolystyrileargglnasnthrleulysleualathrglymetarg
325330335
aatgtaccagaaaagcaaaccagaggaatctttggagcaatagcggga1056
asnvalproglulysglnthrargglyilepheglyalailealagly
340345350
ttcatcgaaaacggctgggaaggaatggttgatgggtggtatgggttc1104
pheilegluasnglytrpgluglymetvalaspglytrptyrglyphe
355360365
cgatatcaaaactctgaaggaacagggcaagctgcagatctaaagagc1152
argtyrglnasnsergluglythrglyglnalaalaaspleulysser
370375380
actcaagcagccatcgaccagattaatggaaagttaaacagagtgatt1200
thrglnalaalaileaspglnileasnglylysleuasnargvalile
385390395400
gaaagaaccaatgagaaattccatcaaatagagaaggaattctcagaa1248
gluargthrasnglulysphehisglnileglulysglupheserglu
405410415
gtagaaggaagaattcaggacttggagaaatatgtagaagacaccaaa1296
valgluglyargileglnaspleuglulystyrvalgluaspthrlys
420425430
atagacctatggtcctacaatgcagaattgctggtggctctagaaaat1344
ileaspleutrpsertyrasnalagluleuleuvalalaleugluasn
435440445
caacatacaattgacttaacagatgcagaaatgaataaattatttgag1392
glnhisthrileaspleuthraspalaglumetasnlysleupheglu
450455460
aagactagacgccagttaagagaaaacgcagaagacatgggaggtgga1440
lysthrargargglnleuarggluasnalagluaspmetglyglygly
465470475480
tgtttcaagatttaccacaaatgtgataatgcatgcattggatcaata1488
cysphelysiletyrhislyscysaspasnalacysileglyserile
485490495
agaactgggacatatgaccattacatatacagagatgaagcattaaac1536
argthrglythrtyrasphistyriletyrargaspglualaleuasn
500505510
aaccgatttcagatcaaaggtgtagagttgaaatcaggctacaaagat1584
asnargpheglnilelysglyvalgluleulysserglytyrlysasp
515520525
tggatactgtggatttcattcgccatatcatgcttcttaatttgcgtt1632
trpileleutrpileserphealailesercyspheleuilecysval
530535540
gttctattgggtttcattatgtgggcttgccaaaaaggcaacatcaga1680
valleuleuglypheilemettrpalacysglnlysglyasnilearg
545550555560
tgcaacatttgcatttga1698
cysasnilecysile
565
<210>32
<211>565
<212>prt
<213>流感病毒
<400>32
metlysthrthrileileleuileleuleuthrhistrpalatyrser
151015
glnasnproileseraspasnasnthralathrleucysleuglyhis
202530
hisalavalalaasnglythrleuvallysthrileseraspaspgln
354045
ilegluvalthrasnalathrgluleuvalglnserilesermetgly
505560
lysilecysasnlyssertyrargileleuaspglyargasncysthr
65707580
leuileaspalametleuglyaspprohiscysaspalapheglntyr
859095
glusertrpaspleupheilegluargserseralapheserasncys
100105110
tyrprotyraspileproasptyralaserleuargserilevalala
115120125
serserglythrleugluphethralagluglyphethrtrpthrgly
130135140
valthrglnasnglyargserglyalacyslysargglyseralaasp
145150155160
serphepheserargleuasntrpleuthrlysserglysersertyr
165170175
prothrleuasnvalthrmetproasnasnlysasnpheasplysleu
180185190
tyriletrpglyilehishisproserserasnglngluglnthrlys
195200205
leutyrileglngluserglyargvalthrvalserthrlysargser
210215220
glnglnthrileileproasnileglyserargproleuvalarggly
225230235240
glnserglyargileseriletyrtrpthrilevallysproglyasp
245250255
ileleumetileasnserasnglyasnleuvalalaproargglytyr
260265270
phelysleulysthrglylysserservalmetargseraspvalpro
275280285
ileaspilecysvalserglucysilethrproasnglyserileser
290295300
asnasplyspropheglnasnvalasnlysvalthrtyrglylyscys
305310315320
prolystyrileargglnasnthrleulysleualathrglymetarg
325330335
asnvalproglulysglnthrargglyilepheglyalailealagly
340345350
pheilegluasnglytrpgluglymetvalaspglytrptyrglyphe
355360365
argtyrglnasnsergluglythrglyglnalaalaaspleulysser
370375380
thrglnalaalaileaspglnileasnglylysleuasnargvalile
385390395400
gluargthrasnglulysphehisglnileglulysglupheserglu
405410415
valgluglyargileglnaspleuglulystyrvalgluaspthrlys
420425430
ileaspleutrpsertyrasnalagluleuleuvalalaleugluasn
435440445
glnhisthrileaspleuthraspalaglumetasnlysleupheglu
450455460
lysthrargargglnleuarggluasnalagluaspmetglyglygly
465470475480
cysphelysiletyrhislyscysaspasnalacysileglyserile
485490495
argthrglythrtyrasphistyriletyrargaspglualaleuasn
500505510
asnargpheglnilelysglyvalgluleulysserglytyrlysasp
515520525
trpileleutrpileserphealailesercyspheleuilecysval
530535540
valleuleuglypheilemettrpalacysglnlysglyasnilearg
545550555560
cysasnilecysile
565
<210>33
<211>549
<212>prt
<213>流感病毒
<400>33
glnasnproileserglyasnasnthralathrleucysleuglyhis
151015
hisalavalalaasnglythrleuvallysthrmetseraspaspgln
202530
ilegluvalthrasnalathrgluleuvalglnserilesermetgly
354045
lysilecysasnlyssertyrargileleuaspglyargasncysthr
505560
leuileaspalametleuglyaspprohiscysaspalapheglntyr
65707580
glusertrpaspleupheilegluargserasnalapheserasncys
859095
tyrprotyraspileproasptyralaserleuargserilevalala
100105110
serserglythrleugluphethralagluglyphethrtrpthrgly
115120125
valthrglnasnglyargserglyalacyslysargglyseralaasp
130135140
serphepheserargleuasntrpleuthrlysserglysersertyr
145150155160
prothrleuasnvalthrmetproasnasnlysasnpheasplysleu
165170175
tyriletrpglyilehishisproserserasnglngluglnthrlys
180185190
leutyrileglngluserglyargvalthrvalserthrlysargser
195200205
glnglnthrileileproasnileglyserargproleuvalarggly
210215220
glnserglyargileseriletyrtrpthrilevallysproglyasp
225230235240
ileleumetileasnserasnglyasnleuvalalaproargglytyr
245250255
phelysleulysthrglylysserservalmetargseraspalapro
260265270
ileaspilecysvalserglucysilethrproasnglyserileser
275280285
asnasplyspropheglnasnvalasnlysvalthrtyrglylyscys
290295300
prolystyrileargglnasnthrleulysleualathrglymetarg
305310315320
asnvalproglulysglnthrargglyilepheglyalailealagly
325330335
pheilegluasnglytrpgluglymetvalaspglytrptyrglyphe
340345350
argtyrglnasnsergluglythrglyglnalaalaaspleulysser
355360365
thrglnalaalaileaspglnileasnglylysleuasnargvalile
370375380
gluargthrasnglulysphehisglnileglulysglupheserglu
385390395400
valgluglyargileglnaspleuglulystyrvalgluaspthrlys
405410415
ileaspleutrpsertyrasnalagluleuleuvalalaleugluasn
420425430
glnhisthrileaspleuthraspalaglumetasnlysleupheglu
435440445
lysthrargargglnleuarggluasnalagluaspmetglyglygly
450455460
cysphelysiletyrhislyscysaspasnalacysileglyserile
465470475480
argthrglythrtyrasphistyriletyrargaspglualaleuasn
485490495
asnargpheglnilelysglyvalgluleulysserglytyrlysasp
500505510
trpileleutrpileserphealailesercyspheleuilecysval
515520525
valleuleuglypheilemettrpalacysglnargglyasnilearg
530535540
cysasnilecysile
545
<210>34
<211>549
<212>prt
<213>流感病毒
<400>34
glnasnproileseraspasnasnthralathrleucysleuglyhis
151015
hisalavalalaasnglythrleuvallysthrileseraspaspgln
202530
ilegluvalthrasnalathrgluleuvalglnserilesermetgly
354045
lysilecysasnlyssertyrargileleuaspglyargasncysthr
505560
leuileaspalametleuglyaspprohiscysaspalapheglntyr
65707580
glusertrpaspleupheilegluargserseralapheserasncys
859095
tyrprotyraspileproasptyralaserleuargserilevalala
100105110
serserglythrleugluphethralagluglyphethrtrpthrgly
115120125
valthrglnasnglyargserglyalacyslysargglyseralaasp
130135140
serphepheserargleuasntrpleuthrlysserglysersertyr
145150155160
prothrleuasnvalthrmetproasnasnlysasnpheasplysleu
165170175
tyriletrpglyilehishisproserserasnglngluglnthrlys
180185190
leutyrileglngluserglyargvalthrvalserthrlysargser
195200205
glnglnthrileileproasnileglyserargproleuvalarggly
210215220
glnserglyargileseriletyrtrpthrilevallysproglyasp
225230235240
ileleumetileasnserasnglyasnleuvalalaproargglytyr
245250255
phelysleulysthrglylysserservalmetargseraspvalpro
260265270
ileaspilecysvalserglucysilethrproasnglyserileser
275280285
asnasplyspropheglnasnvalasnlysvalthrtyrglylyscys
290295300
prolystyrileargglnasnthrleulysleualathrglymetarg
305310315320
asnvalproglulysglnthrargglyilepheglyalailealagly
325330335
pheilegluasnglytrpgluglymetvalaspglytrptyrglyphe
340345350
argtyrglnasnsergluglythrglyglnalaalaaspleulysser
355360365
thrglnalaalaileaspglnileasnglylysleuasnargvalile
370375380
gluargthrasnglulysphehisglnileglulysglupheserglu
385390395400
valgluglyargileglnaspleuglulystyrvalgluaspthrlys
405410415
ileaspleutrpsertyrasnalagluleuleuvalalaleugluasn
420425430
glnhisthrileaspleuthraspalaglumetasnlysleupheglu
435440445
lysthrargargglnleuarggluasnalagluaspmetglyglygly
450455460
cysphelysiletyrhislyscysaspasnalacysileglyserile
465470475480
argthrglythrtyrasphistyriletyrargaspglualaleuasn
485490495
asnargpheglnilelysglyvalgluleulysserglytyrlysasp
500505510
trpileleutrpileserphealailesercyspheleuilecysval
515520525
valleuleuglypheilemettrpalacysglnlysglyasnilearg
530535540
cysasnilecysile
545
<210>35
<211>9
<212>dna
<213>流感病毒
<400>35
gagagttgg9
<210>36
<211>9
<212>dna
<213>流感病毒
<400>36
ccgttggtc9
<210>37
<211>9
<212>dna
<213>流感病毒
<400>37
caaaccaga9
<210>38
<211>9
<212>dna
<213>流感病毒
<400>38
agaactggg9
<210>39
<211>15
<212>dna
<213>流感病毒
<400>39
tatgagagttgggac15
<210>40
<211>15
<212>dna
<213>流感病毒
<400>40
agaccgttggtcaga15
<210>41
<211>15
<212>dna
<213>流感病毒
<400>41
aagcaaaccagagga15
<210>42
<211>15
<212>dna
<213>流感病毒
<400>42
ataagaactgggaca15
<210>43
<211>9
<212>dna
<213>流感病毒
<400>43
acaatgagt9
<210>44
<211>15
<212>dna
<213>流感病毒
<400>44
aaaacaatgagtgat15
<210>45
<211>9
<212>dna
<213>流感病毒
<400>45
gatgtaccc9
<210>46
<211>15
<212>dna
<213>流感病毒
<400>46
tcagatgtacccata15
<210>47
<211>2280
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(2280)
<400>47
atggagagaataaaagaactgagagatctgatgttacaatcccgcacc48
metgluargilelysgluleuargaspleumetleuglnserargthr
151015
cgcgagatactaacaaaaactactgtggaccacatggccataatcaag96
arggluileleuthrlysthrthrvalasphismetalaileilelys
202530
aaatacacatcaggaagacaagagaagaaccctgcacttaggatgaaa144
lystyrthrserglyargglnglulysasnproalaleuargmetlys
354045
tggatgatggcaatgaaatacccaattacagcagataagaggataatg192
trpmetmetalametlystyrproilethralaasplysargilemet
505560
gagatgattcctgagagaaatgaacagggacaaaccctttggagcaaa240
glumetileprogluargasngluglnglyglnthrleutrpserlys
65707580
acgaacgatgctggctcagaccgcgtaatggtatcacctctggcagtg288
thrasnaspalaglyseraspargvalmetvalserproleualaval
859095
acatggtggaataggaatggaccaacaacgaacacaattcattatcca336
thrtrptrpasnargasnglyprothrthrasnthrilehistyrpro
100105110
aaagtctacaaaacttattttgaaaaggttgaaagattgaaacacgga384
lysvaltyrlysthrtyrpheglulysvalgluargleulyshisgly
115120125
acctttggccccgttcattttaggaatcaagtcaagataagacgaaga432
thrpheglyprovalhispheargasnglnvallysileargargarg
130135140
gttgatgtaaaccctggtcacgcggacctcagtgctaaagaagcacaa480
valaspvalasnproglyhisalaaspleuseralalysglualagln
145150155160
gatgtgatcatggaagttgttttcccaaatgaagtgggagccagaatt528
aspvalilemetgluvalvalpheproasngluvalglyalaargile
165170175
ctaacatcagaatcacaactaacaataaccaaagagaaaaaggaagaa576
leuthrsergluserglnleuthrilethrlysglulyslysgluglu
180185190
cttcaggactgcaaaattgctcccttgatggtagcatacatgctagaa624
leuglnaspcyslysilealaproleumetvalalatyrmetleuglu
195200205
agagagttggtccgaaaaacaaggttcctcccagtagtaggcggaaca672
arggluleuvalarglysthrargpheleuprovalvalglyglythr
210215220
agcagtgtatacattgaagtgttgcatctgactcagggaacatgctgg720
serservaltyrilegluvalleuhisleuthrglnglythrcystrp
225230235240
gagcaaatgtacaccccaggaggaaaagttagaaacgatgatattgat768
gluglnmettyrthrproglyglylysvalargasnaspaspileasp
245250255
caaagtttaattattgcagcccggaacatagtgagaagagcaacagta816
glnserleuileilealaalaargasnilevalargargalathrval
260265270
tcagcagatccactagcatccctactggaaatgtgccacagtacacag864
seralaaspproleualaserleuleuglumetcyshisserthrgln
275280285
attggtggaacaaggatggtagacatccttaagcagaacccaacagag912
ileglyglythrargmetvalaspileleulysglnasnprothrglu
290295300
gaacaagctgtggatatatgcaaagcagcaatgggattgagaattagc960
gluglnalavalaspilecyslysalaalametglyleuargileser
305310315320
tcatcattcagctttggtggattcaccttcaaaaggacaagtggatca1008
serserpheserpheglyglyphethrphelysargthrserglyser
325330335
tcagtcaagagagaagaagaaatgcttacgggcaaccttcaaacattg1056
servallysargglugluglumetleuthrglyasnleuglnthrleu
340345350
aaaataagagtgcatgagggctatgaagaattcacaatggtcggaaga1104
lysileargvalhisgluglytyrglugluphethrmetvalglyarg
355360365
agagcaacagccattatcagaaaggcaaccagaagattgattcaattg1152
argalathralaileilearglysalathrargargleuileglnleu
370375380
atagtaagtgggagagatgaacaatcaattgctgaagcaataattgta1200
ilevalserglyargaspgluglnserilealaglualaileileval
385390395400
gccatggtgttttcgcaagaagattgcatgataaaagcagttcgaggc1248
alametvalpheserglngluaspcysmetilelysalavalarggly
405410415
gatttgaactttgttaatagagcaaatcagcgtttgaaccccatgcat1296
aspleuasnphevalasnargalaasnglnargleuasnpromethis
420425430
caactcttgaggcatttccaaaaagatgcaaaagtgcttttccaaaat1344
glnleuleuarghispheglnlysaspalalysvalleupheglnasn
435440445
tggggaattgaacccatcgacaatgtaatggggatgattggaatattg1392
trpglyilegluproileaspasnvalmetglymetileglyileleu
450455460
cctgacatgaccccaagcaccgagatgtcattgagaggagtgagagtc1440
proaspmetthrproserthrglumetserleuargglyvalargval
465470475480
agcaaaatgggagtggatgagtactccagcactgagagagtggtggtg1488
serlysmetglyvalaspglutyrserserthrgluargvalvalval
485490495
agcattgaccgttttttaagagttcgggatcaaaggggaaacatacta1536
serileaspargpheleuargvalargaspglnargglyasnileleu
500505510
ctgtcccctgaagaagtcagtgaaacacaaggaacggaaaagctgaca1584
leuserproglugluvalsergluthrglnglythrglulysleuthr
515520525
ataatttattcgtcatcaatgatgtgggagattaatggtcccgaatca1632
ileiletyrsersersermetmettrpgluileasnglyprogluser
530535540
gtgttggtcaatacttatcaatggatcatcagaaactgggaaattgta1680
valleuvalasnthrtyrglntrpileileargasntrpgluileval
545550555560
aaaattcagtggtcacaggaccccacaatgttatacaataagatagaa1728
lysileglntrpserglnaspprothrmetleutyrasnlysileglu
565570575
tttgaaccattccaatccctggtccctagggccaccagaagccaatac1776
pheglupropheglnserleuvalproargalathrargserglntyr
580585590
agcggtttcgtaagaaccctgtttcagcaaatgcgagatgtacttgga1824
serglyphevalargthrleupheglnglnmetargaspvalleugly
595600605
acatttgatactgctcaaataataaaactcctcccttttgccgctgct1872
thrpheaspthralaglnileilelysleuleuprophealaalaala
610615620
cctccggaacagagtaggatgcagttctcttctttgactgttaatgta1920
proprogluglnserargmetglnpheserserleuthrvalasnval
625630635640
agaggttcgggaatgaggatacttgtaagaggcaattccccagtgttc1968
argglyserglymetargileleuvalargglyasnserprovalphe
645650655
aactacaataaagtcactaaaaggctcacagtcctcggaaaggatgca2016
asntyrasnlysvalthrlysargleuthrvalleuglylysaspala
660665670
ggtgcgcttactgaggacccagatgaaggtacggctggagtagagtct2064
glyalaleuthrgluaspproaspgluglythralaglyvalgluser
675680685
gctgttctaagagggtttctcattttaggtaaagaaaacaagagatat2112
alavalleuargglypheleuileleuglylysgluasnlysargtyr
690695700
ggcccagcactaagcatcaatgaacttagcaaacttgcaaaaggggag2160
glyproalaleuserileasngluleuserlysleualalysglyglu
705710715720
aaagccaatgtactaattgggcaaggggacgtagtgttggtaatgaaa2208
lysalaasnvalleuileglyglnglyaspvalvalleuvalmetlys
725730735
cggaaacgtgactctagcatacttactgacagccagacagcgaccaaa2256
arglysargaspserserileleuthraspserglnthralathrlys
740745750
aggattcggatggccatcaattag2280
argileargmetalaileasn
755
<210>48
<211>759
<212>prt
<213>流感病毒
<400>48
metgluargilelysgluleuargaspleumetleuglnserargthr
151015
arggluileleuthrlysthrthrvalasphismetalaileilelys
202530
lystyrthrserglyargglnglulysasnproalaleuargmetlys
354045
trpmetmetalametlystyrproilethralaasplysargilemet
505560
glumetileprogluargasngluglnglyglnthrleutrpserlys
65707580
thrasnaspalaglyseraspargvalmetvalserproleualaval
859095
thrtrptrpasnargasnglyprothrthrasnthrilehistyrpro
100105110
lysvaltyrlysthrtyrpheglulysvalgluargleulyshisgly
115120125
thrpheglyprovalhispheargasnglnvallysileargargarg
130135140
valaspvalasnproglyhisalaaspleuseralalysglualagln
145150155160
aspvalilemetgluvalvalpheproasngluvalglyalaargile
165170175
leuthrsergluserglnleuthrilethrlysglulyslysgluglu
180185190
leuglnaspcyslysilealaproleumetvalalatyrmetleuglu
195200205
arggluleuvalarglysthrargpheleuprovalvalglyglythr
210215220
serservaltyrilegluvalleuhisleuthrglnglythrcystrp
225230235240
gluglnmettyrthrproglyglylysvalargasnaspaspileasp
245250255
glnserleuileilealaalaargasnilevalargargalathrval
260265270
seralaaspproleualaserleuleuglumetcyshisserthrgln
275280285
ileglyglythrargmetvalaspileleulysglnasnprothrglu
290295300
gluglnalavalaspilecyslysalaalametglyleuargileser
305310315320
serserpheserpheglyglyphethrphelysargthrserglyser
325330335
servallysargglugluglumetleuthrglyasnleuglnthrleu
340345350
lysileargvalhisgluglytyrglugluphethrmetvalglyarg
355360365
argalathralaileilearglysalathrargargleuileglnleu
370375380
ilevalserglyargaspgluglnserilealaglualaileileval
385390395400
alametvalpheserglngluaspcysmetilelysalavalarggly
405410415
aspleuasnphevalasnargalaasnglnargleuasnpromethis
420425430
glnleuleuarghispheglnlysaspalalysvalleupheglnasn
435440445
trpglyilegluproileaspasnvalmetglymetileglyileleu
450455460
proaspmetthrproserthrglumetserleuargglyvalargval
465470475480
serlysmetglyvalaspglutyrserserthrgluargvalvalval
485490495
serileaspargpheleuargvalargaspglnargglyasnileleu
500505510
leuserproglugluvalsergluthrglnglythrglulysleuthr
515520525
ileiletyrsersersermetmettrpgluileasnglyprogluser
530535540
valleuvalasnthrtyrglntrpileileargasntrpgluileval
545550555560
lysileglntrpserglnaspprothrmetleutyrasnlysileglu
565570575
pheglupropheglnserleuvalproargalathrargserglntyr
580585590
serglyphevalargthrleupheglnglnmetargaspvalleugly
595600605
thrpheaspthralaglnileilelysleuleuprophealaalaala
610615620
proprogluglnserargmetglnpheserserleuthrvalasnval
625630635640
argglyserglymetargileleuvalargglyasnserprovalphe
645650655
asntyrasnlysvalthrlysargleuthrvalleuglylysaspala
660665670
glyalaleuthrgluaspproaspgluglythralaglyvalgluser
675680685
alavalleuargglypheleuileleuglylysgluasnlysargtyr
690695700
glyproalaleuserileasngluleuserlysleualalysglyglu
705710715720
lysalaasnvalleuileglyglnglyaspvalvalleuvalmetlys
725730735
arglysargaspserserileleuthraspserglnthralathrlys
740745750
argileargmetalaileasn
755
<210>49
<211>2274
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(2274)
<400>49
atggatgtcaatccgactctacttttcttaaaggtgccagcgcaaaat48
metaspvalasnprothrleuleupheleulysvalproalaglnasn
151015
gctataagcacaacattcccttatactggagatcctccctacagtcat96
alaileserthrthrpheprotyrthrglyaspproprotyrserhis
202530
ggaacagggacaggatacaccatggatactgtcaacagaacacaccaa144
glythrglythrglytyrthrmetaspthrvalasnargthrhisgln
354045
tattcagaaaaagggaaatggacaacaaacactgagattggagcacca192
tyrserglulysglylystrpthrthrasnthrgluileglyalapro
505560
caacttaatccaatcgatggaccacttcctgaagacaatgaaccaagt240
glnleuasnproileaspglyproleuprogluaspasngluproser
65707580
gggtacgcccaaacagattgtgtattggaagcaatggctttccttgaa288
glytyralaglnthraspcysvalleuglualametalapheleuglu
859095
gaatcccatcccggaatctttgaaaattcgtgtcttgaaacgatggag336
gluserhisproglyilephegluasnsercysleugluthrmetglu
100105110
gtgattcagcagacaagagtggacaaactaacacaaggccgacaaact384
valileglnglnthrargvalasplysleuthrglnglyargglnthr
115120125
tatgattggaccttgaataggaatcaacctgccgcaacagcacttgct432
tyrasptrpthrleuasnargasnglnproalaalathralaleuala
130135140
aatacgattgaagtattcagatcaaatggtctgacctccaatgaatcg480
asnthrilegluvalpheargserasnglyleuthrserasngluser
145150155160
gggagattgatggacttcctcaaagatgtcatggagtccatgaacaag528
glyargleumetasppheleulysaspvalmetglusermetasnlys
165170175
gaggaaatggaaataacaacacacttccaacggaagagaagagtaaga576
gluglumetgluilethrthrhispheglnarglysargargvalarg
180185190
gacaacatgacaaagagaatgataacacagagaaccataggaaagaaa624
aspasnmetthrlysargmetilethrglnargthrileglylyslys
195200205
aaacaacgattaagcagaaagagctatctaatcagaacattaacccta672
lysglnargleuserarglyssertyrleuileargthrleuthrleu
210215220
aacacaatgaccaaggacgctgagagagggaaattgaaacgacgagca720
asnthrmetthrlysaspalagluargglylysleulysargargala
225230235240
atcgctaccccagggatgcagataagaggatttgtatattttgttgaa768
ilealathrproglymetglnileargglyphevaltyrphevalglu
245250255
acactagctcgaagaatatgtgaaaagcttgaacaatcaggattgcca816
thrleualaargargilecysglulysleugluglnserglyleupro
260265270
gttggcggtaatgagaaaaaggccaaactggctaatgtcgtcagaaaa864
valglyglyasnglulyslysalalysleualaasnvalvalarglys
275280285
atgatgactaattcccaagacactgaactctccttcaccatcactggg912
metmetthrasnserglnaspthrgluleuserphethrilethrgly
290295300
gacaataccaaatggaatgaaaatcagaacccacgcatattcctggca960
aspasnthrlystrpasngluasnglnasnproargilepheleuala
305310315320
atgatcacatacataactagagatcagccagaatggttcagaaatgtt1008
metilethrtyrilethrargaspglnproglutrppheargasnval
325330335
ctaagcattgcaccgattatgttctcaaataaaatggcaagactgggg1056
leuserilealaproilemetpheserasnlysmetalaargleugly
340345350
aaaggatatatgtttgaaagcaaaagtatgaaattgagaactcaaata1104
lysglytyrmetphegluserlyssermetlysleuargthrglnile
355360365
ccagcagaaatgctagcaagcattgacctaaaatatttcaatgattca1152
proalaglumetleualaserileaspleulystyrpheasnaspser
370375380
acaaaaaagaaaattgaaaagatacgaccactcctggttgacgggact1200
thrlyslyslysileglulysileargproleuleuvalaspglythr
385390395400
gcttcactgagtcctggcatgatgatgggaatgttcaacatgttgagc1248
alaserleuserproglymetmetmetglymetpheasnmetleuser
405410415
actgtgctgggtgtatccatattaaacctgggccagaggaaatataca1296
thrvalleuglyvalserileleuasnleuglyglnarglystyrthr
420425430
aagaccacatactggtgggatggtctgcaatcatccgatgactttgct1344
lysthrthrtyrtrptrpaspglyleuglnserseraspasppheala
435440445
ttgatagtgaatgcgcctaatcatgaaggaatacaagctggagtagac1392
leuilevalasnalaproasnhisgluglyileglnalaglyvalasp
450455460
agattctatagaacttgcaaactggtcgggatcaacatgagcaaaaag1440
argphetyrargthrcyslysleuvalglyileasnmetserlyslys
465470475480
aagtcctacataaatagaactggaacattcgaattcacaagctttttc1488
lyssertyrileasnargthrglythrphegluphethrserphephe
485490495
taccggtatggttttgtagccaatttcagcatggaactacccagtttt1536
tyrargtyrglyphevalalaasnphesermetgluleuproserphe
500505510
ggggtttccggaataaatgaatctgcagacatgagcattggagtgaca1584
glyvalserglyileasngluseralaaspmetserileglyvalthr
515520525
gtcatcaaaaacaacatgataaataatgatctcggtcctgccacggca1632
valilelysasnasnmetileasnasnaspleuglyproalathrala
530535540
caaatggcactccaactcttcattaaggattatcggtacacataccgg1680
glnmetalaleuglnleupheilelysasptyrargtyrthrtyrarg
545550555560
tgccatagaggtgatacccagatacaaaccagaagatcttttgagttg1728
cyshisargglyaspthrglnileglnthrargargserphegluleu
565570575
aagaaactgtgggaacagactcgatcaaagactggtctactggtatca1776
lyslysleutrpgluglnthrargserlysthrglyleuleuvalser
580585590
gatgggggtccaaacctatataacatcagaaacctacacatcccggaa1824
aspglyglyproasnleutyrasnileargasnleuhisileproglu
595600605
gtctgtttaaaatgggagctaatggatgaagattataaggggaggcta1872
valcysleulystrpgluleumetaspgluasptyrlysglyargleu
610615620
tgcaatccattgaatcctttcgttagtcacaaagaaattgaatcagtc1920
cysasnproleuasnprophevalserhislysgluilegluserval
625630635640
aacagtgcagtagtaatgcctgctcatggccctgccaaaagcatggag1968
asnseralavalvalmetproalahisglyproalalyssermetglu
645650655
tatgatgctgttgcaacaacacattcttggatccccaagaggaaccgg2016
tyraspalavalalathrthrhissertrpileprolysargasnarg
660665670
tccatattgaacacaagccaaaggggaatactagaagatgagcagatg2064
serileleuasnthrserglnargglyileleugluaspgluglnmet
675680685
tatcagaaatgctgcaacctgtttgaaaaattcttccccagcagctca2112
tyrglnlyscyscysasnleupheglulysphepheproserserser
690695700
tacagaagaccagtcggaatttctagtatggttgaggccatggtatcc2160
tyrargargprovalglyilesersermetvalglualametvalser
705710715720
agggcccgcattgatgcacgaattgacttcgaatctggacggataaag2208
argalaargileaspalaargileaspphegluserglyargilelys
725730735
aaggatgagttcgctgagatcatgaagatctgttccaccattgaagag2256
lysaspgluphealagluilemetlysilecysserthrilegluglu
740745750
ctcagacggcaaaaatag2274
leuargargglnlys
755
<210>50
<211>757
<212>prt
<213>流感病毒
<400>50
metaspvalasnprothrleuleupheleulysvalproalaglnasn
151015
alaileserthrthrpheprotyrthrglyaspproprotyrserhis
202530
glythrglythrglytyrthrmetaspthrvalasnargthrhisgln
354045
tyrserglulysglylystrpthrthrasnthrgluileglyalapro
505560
glnleuasnproileaspglyproleuprogluaspasngluproser
65707580
glytyralaglnthraspcysvalleuglualametalapheleuglu
859095
gluserhisproglyilephegluasnsercysleugluthrmetglu
100105110
valileglnglnthrargvalasplysleuthrglnglyargglnthr
115120125
tyrasptrpthrleuasnargasnglnproalaalathralaleuala
130135140
asnthrilegluvalpheargserasnglyleuthrserasngluser
145150155160
glyargleumetasppheleulysaspvalmetglusermetasnlys
165170175
gluglumetgluilethrthrhispheglnarglysargargvalarg
180185190
aspasnmetthrlysargmetilethrglnargthrileglylyslys
195200205
lysglnargleuserarglyssertyrleuileargthrleuthrleu
210215220
asnthrmetthrlysaspalagluargglylysleulysargargala
225230235240
ilealathrproglymetglnileargglyphevaltyrphevalglu
245250255
thrleualaargargilecysglulysleugluglnserglyleupro
260265270
valglyglyasnglulyslysalalysleualaasnvalvalarglys
275280285
metmetthrasnserglnaspthrgluleuserphethrilethrgly
290295300
aspasnthrlystrpasngluasnglnasnproargilepheleuala
305310315320
metilethrtyrilethrargaspglnproglutrppheargasnval
325330335
leuserilealaproilemetpheserasnlysmetalaargleugly
340345350
lysglytyrmetphegluserlyssermetlysleuargthrglnile
355360365
proalaglumetleualaserileaspleulystyrpheasnaspser
370375380
thrlyslyslysileglulysileargproleuleuvalaspglythr
385390395400
alaserleuserproglymetmetmetglymetpheasnmetleuser
405410415
thrvalleuglyvalserileleuasnleuglyglnarglystyrthr
420425430
lysthrthrtyrtrptrpaspglyleuglnserseraspasppheala
435440445
leuilevalasnalaproasnhisgluglyileglnalaglyvalasp
450455460
argphetyrargthrcyslysleuvalglyileasnmetserlyslys
465470475480
lyssertyrileasnargthrglythrphegluphethrserphephe
485490495
tyrargtyrglyphevalalaasnphesermetgluleuproserphe
500505510
glyvalserglyileasngluseralaaspmetserileglyvalthr
515520525
valilelysasnasnmetileasnasnaspleuglyproalathrala
530535540
glnmetalaleuglnleupheilelysasptyrargtyrthrtyrarg
545550555560
cyshisargglyaspthrglnileglnthrargargserphegluleu
565570575
lyslysleutrpgluglnthrargserlysthrglyleuleuvalser
580585590
aspglyglyproasnleutyrasnileargasnleuhisileproglu
595600605
valcysleulystrpgluleumetaspgluasptyrlysglyargleu
610615620
cysasnproleuasnprophevalserhislysgluilegluserval
625630635640
asnseralavalvalmetproalahisglyproalalyssermetglu
645650655
tyraspalavalalathrthrhissertrpileprolysargasnarg
660665670
serileleuasnthrserglnargglyileleugluaspgluglnmet
675680685
tyrglnlyscyscysasnleupheglulysphepheproserserser
690695700
tyrargargprovalglyilesersermetvalglualametvalser
705710715720
argalaargileaspalaargileaspphegluserglyargilelys
725730735
lysaspgluphealagluilemetlysilecysserthrilegluglu
740745750
leuargargglnlys
755
<210>51
<211>2151
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(2151)
<400>51
atggaagactttgtgcgacagtgcttcaatccaatgatcgtcgagctt48
metgluaspphevalargglncyspheasnprometilevalgluleu
151015
gcggaaaaggcaatgaaagaatatggagagaacccgaaaatcgaaaca96
alaglulysalametlysglutyrglygluasnprolysilegluthr
202530
aacaaatttgcagcaatatgcactcacttggaagtctgcttcatgtac144
asnlysphealaalailecysthrhisleugluvalcysphemettyr
354045
tcggatttccactttataaatgaactgggtgagtcagtggtcatagag192
seraspphehispheileasngluleuglygluservalvalileglu
505560
tctggtgacccaaatgctcttttgaaacacagatttgaaatcattgag240
serglyaspproasnalaleuleulyshisargphegluileileglu
65707580
gggagagatcgaacaatggcatggacagtagtaaacagcatctgcaac288
glyargaspargthrmetalatrpthrvalvalasnserilecysasn
859095
accacaagagctgaaaaacctaaatttcttccagatttatacgactat336
thrthrargalaglulysprolyspheleuproaspleutyrasptyr
100105110
aaagagaacagatttgttgaaattggtgtgacaaggagagaagttcac384
lysgluasnargphevalgluileglyvalthrargarggluvalhis
115120125
atatactacctggagaaggccaacaaaataaagtctgagaaaacacat432
iletyrtyrleuglulysalaasnlysilelysserglulysthrhis
130135140
atccacattttctcatttacaggagaagaaatggctacaaaagcggac480
ilehisilepheserphethrglygluglumetalathrlysalaasp
145150155160
tatactcttgatgaagagagtagagccaggatcaagaccagactattc528
tyrthrleuaspglugluserargalaargilelysthrargleuphe
165170175
actataagacaagaaatggccagtagaggcctctgggattcctttcgt576
thrileargglnglumetalaserargglyleutrpaspserphearg
180185190
cagtccgagagaggcgaagagacaattgaagaaagatttgaaatcaca624
glnsergluargglyglugluthrileglugluargphegluilethr
195200205
gggacgatgcgcaagcttgccaattacagtctcccaccgaacttctcc672
glythrmetarglysleualaasntyrserleuproproasnpheser
210215220
agccttgaaaattttagagtctatatagatggattcgaaccgaacggc720
serleugluasnpheargvaltyrileaspglyphegluproasngly
225230235240
tgcattgagagtaagctttctcaaatgtccaaagaagtaaatgccaaa768
cysilegluserlysleuserglnmetserlysgluvalasnalalys
245250255
atagaaccattttcaaagacaacaccccgaccactcaaaatgccaggt816
ileglupropheserlysthrthrproargproleulysmetprogly
260265270
ggtccaccctgccatcagcgatccaaattcttgctaatggatgctctg864
glyproprocyshisglnargserlyspheleuleumetaspalaleu
275280285
aaactgagcattgaggacccaagtcacgagggagaggggataccacta912
lysleuserilegluaspproserhisgluglygluglyileproleu
290295300
tatgatgcaatcaaatgcatgaaaactttctttggatggaaagagccc960
tyraspalailelyscysmetlysthrphepheglytrplysglupro
305310315320
agtattgttaaaccacataaaaagggtataaacccgaactatctccaa1008
serilevallysprohislyslysglyileasnproasntyrleugln
325330335
acttggaagcaagtattagaagaaatacaagaccttgagaacgaagaa1056
thrtrplysglnvalleuglugluileglnaspleugluasngluglu
340345350
aggacccccaagaccaagaatatgaaaaaaacaagccaattgaaatgg1104
argthrprolysthrlysasnmetlyslysthrserglnleulystrp
355360365
gcactaggtgaaaatatggcaccagagaaagtggattttgaggattgt1152
alaleuglygluasnmetalaproglulysvalaspphegluaspcys
370375380
aaagacatcaatgatttaaaacaatatgacagtgatgagccagaagca1200
lysaspileasnaspleulysglntyraspseraspgluprogluala
385390395400
aggtctcttgcaagttggattcaaagtgagttcaacaaggcttgtgag1248
argserleualasertrpileglnserglupheasnlysalacysglu
405410415
ctgacagattcaagctggatagagctcgatgaaattggggaggatgtc1296
leuthraspsersertrpilegluleuaspgluileglygluaspval
420425430
gccccaatagaatacattgcgagcatgaggagaaattattttactgct1344
alaproileglutyrilealasermetargargasntyrphethrala
435440445
gagatttcccattgtagagcaacagaatatataatgaaaggagtgtac1392
gluileserhiscysargalathrglutyrilemetlysglyvaltyr
450455460
atcaacactgctctactcaatgcatcctgtgctgcgatggatgaattt1440
ileasnthralaleuleuasnalasercysalaalametaspgluphe
465470475480
caattaattccgatgataagtaaatgcaggaccaaagaagggagaagg1488
glnleuileprometileserlyscysargthrlysgluglyargarg
485490495
aaaacaaatttatatggattcataataaagggaaggtcccatttaaga1536
lysthrasnleutyrglypheileilelysglyargserhisleuarg
500505510
aatgatactgacgtggtgaactttgtaagtatggaattttctctcact1584
asnaspthraspvalvalasnphevalsermetglupheserleuthr
515520525
gatccaagatttgagccacacaaatgggaaaaatactgcgttctagaa1632
aspproargphegluprohislystrpglulystyrcysvalleuglu
530535540
attggagacatgcttttaagaactgctgtaggtcaagtgtcaagaccc1680
ileglyaspmetleuleuargthralavalglyglnvalserargpro
545550555560
atgtttttgtatgtaaggacaaatggaacctctaaaattaaaatgaaa1728
metpheleutyrvalargthrasnglythrserlysilelysmetlys
565570575
tggggaatggaaatgaggcgctgcctccttcagtctctgcaacagatt1776
trpglymetglumetargargcysleuleuglnserleuglnglnile
580585590
gaaagcatgatcgaagctgagtcctcagtcaaagaaaaggacatgacc1824
glusermetileglualagluserservallysglulysaspmetthr
595600605
aaagaattttttgagaacaaatcagagacatggcctataggagagtcc1872
lysgluphephegluasnlyssergluthrtrpproileglygluser
610615620
cccaaaggagtggaagagggctcaatcgggaaggtttgcaggacctta1920
prolysglyvalglugluglyserileglylysvalcysargthrleu
625630635640
ttagcaaaatctgtgtttaacagtttatatgcatctccacaactggaa1968
leualalysservalpheasnserleutyralaserproglnleuglu
645650655
ggattttcagctgaatctaggaaattacttctcattgttcaggctctt2016
glypheseralagluserarglysleuleuleuilevalglnalaleu
660665670
agagatgacctggaacctggaacctttgatattggggggttatatgaa2064
argaspaspleugluproglythrpheaspileglyglyleutyrglu
675680685
tcaattgaggagtgcctgattaatgatccctgggttttgcttaatgca2112
serilegluglucysleuileasnaspprotrpvalleuleuasnala
690695700
tcttggttcaactccttcctcacacatgcactgaagtag2151
sertrppheasnserpheleuthrhisalaleulys
705710715
<210>52
<211>716
<212>prt
<213>流感病毒
<400>52
metgluaspphevalargglncyspheasnprometilevalgluleu
151015
alaglulysalametlysglutyrglygluasnprolysilegluthr
202530
asnlysphealaalailecysthrhisleugluvalcysphemettyr
354045
seraspphehispheileasngluleuglygluservalvalileglu
505560
serglyaspproasnalaleuleulyshisargphegluileileglu
65707580
glyargaspargthrmetalatrpthrvalvalasnserilecysasn
859095
thrthrargalaglulysprolyspheleuproaspleutyrasptyr
100105110
lysgluasnargphevalgluileglyvalthrargarggluvalhis
115120125
iletyrtyrleuglulysalaasnlysilelysserglulysthrhis
130135140
ilehisilepheserphethrglygluglumetalathrlysalaasp
145150155160
tyrthrleuaspglugluserargalaargilelysthrargleuphe
165170175
thrileargglnglumetalaserargglyleutrpaspserphearg
180185190
glnsergluargglyglugluthrileglugluargphegluilethr
195200205
glythrmetarglysleualaasntyrserleuproproasnpheser
210215220
serleugluasnpheargvaltyrileaspglyphegluproasngly
225230235240
cysilegluserlysleuserglnmetserlysgluvalasnalalys
245250255
ileglupropheserlysthrthrproargproleulysmetprogly
260265270
glyproprocyshisglnargserlyspheleuleumetaspalaleu
275280285
lysleuserilegluaspproserhisgluglygluglyileproleu
290295300
tyraspalailelyscysmetlysthrphepheglytrplysglupro
305310315320
serilevallysprohislyslysglyileasnproasntyrleugln
325330335
thrtrplysglnvalleuglugluileglnaspleugluasngluglu
340345350
argthrprolysthrlysasnmetlyslysthrserglnleulystrp
355360365
alaleuglygluasnmetalaproglulysvalaspphegluaspcys
370375380
lysaspileasnaspleulysglntyraspseraspgluprogluala
385390395400
argserleualasertrpileglnserglupheasnlysalacysglu
405410415
leuthraspsersertrpilegluleuaspgluileglygluaspval
420425430
alaproileglutyrilealasermetargargasntyrphethrala
435440445
gluileserhiscysargalathrglutyrilemetlysglyvaltyr
450455460
ileasnthralaleuleuasnalasercysalaalametaspgluphe
465470475480
glnleuileprometileserlyscysargthrlysgluglyargarg
485490495
lysthrasnleutyrglypheileilelysglyargserhisleuarg
500505510
asnaspthraspvalvalasnphevalsermetglupheserleuthr
515520525
aspproargphegluprohislystrpglulystyrcysvalleuglu
530535540
ileglyaspmetleuleuargthralavalglyglnvalserargpro
545550555560
metpheleutyrvalargthrasnglythrserlysilelysmetlys
565570575
trpglymetglumetargargcysleuleuglnserleuglnglnile
580585590
glusermetileglualagluserservallysglulysaspmetthr
595600605
lysgluphephegluasnlyssergluthrtrpproileglygluser
610615620
prolysglyvalglugluglyserileglylysvalcysargthrleu
625630635640
leualalysservalpheasnserleutyralaserproglnleuglu
645650655
glypheseralagluserarglysleuleuleuilevalglnalaleu
660665670
argaspaspleugluproglythrpheaspileglyglyleutyrglu
675680685
serilegluglucysleuileasnaspprotrpvalleuleuasnala
690695700
sertrppheasnserpheleuthrhisalaleulys
705710715
<210>53
<211>844
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(690)
<400>53
atggattccaacactgtgtcaagctttcaggtagactgttttctttgg48
metaspserasnthrvalserserpheglnvalaspcyspheleutrp
151015
catgtccgtaaacgattcgcagaccaagaactgggtgatgccccattc96
hisvalarglysargphealaaspglngluleuglyaspalaprophe
202530
cttgaccggcttcgccgagaccagaagtccctaaggggaagaggtagc144
leuaspargleuargargaspglnlysserleuargglyargglyser
354045
actcttggtctggacatcgaaacagccactcatgcaggaaagcagata192
thrleuglyleuaspilegluthralathrhisalaglylysglnile
505560
gtggagcagattctggaaaaggaatcagatgaggcacttaaaatgacc240
valgluglnileleuglulysgluseraspglualaleulysmetthr
65707580
attgcctctgttcctgcttcacgctacttaactgacatgactcttgat288
ilealaservalproalaserargtyrleuthraspmetthrleuasp
859095
gagatgtcaagagactggttcatgctcatgcccaagcaaaaagtaaca336
glumetserargasptrpphemetleumetprolysglnlysvalthr
100105110
ggctccctatgtataagaatggaccaggcaatcatggataagaacatc384
glyserleucysileargmetaspglnalailemetasplysasnile
115120125
atacttaaagcaaactttagtgtgattttcgaaaggctggaaacacta432
ileleulysalaasnpheservalilephegluargleugluthrleu
130135140
atactacttagagccttcaccgaagaaggagcagtcgttggcgaaatt480
ileleuleuargalaphethrglugluglyalavalvalglygluile
145150155160
tcaccattaccttctcttccaggacatactaatgaggatgtcaaaaat528
serproleuproserleuproglyhisthrasngluaspvallysasn
165170175
gcaattggggtcctcatcggaggacttaaatggaatgataatacggtt576
alaileglyvalleuileglyglyleulystrpasnaspasnthrval
180185190
agaatctctgaaactctacagagattcgcttggagaagcagtcatgaa624
argilesergluthrleuglnargphealatrpargserserhisglu
195200205
aatgggagaccttcattcccttcaaaacagaaacgaaaaatggagaga672
asnglyargproserpheproserlysglnlysarglysmetgluarg
210215220
acaattaagccagaaatttgaagaaataagatggttgattgaagaagt720
thrilelysprogluile
225230
gcgacatagattgaaaaatacagaaaatagttttgaacaaataacatttatgcaagcctt780
acaactattgcttgaagtagaacaagagataagaactttctcgtttcagcttatttaatg840
ataa844
<210>54
<211>230
<212>prt
<213>流感病毒
<400>54
metaspserasnthrvalserserpheglnvalaspcyspheleutrp
151015
hisvalarglysargphealaaspglngluleuglyaspalaprophe
202530
leuaspargleuargargaspglnlysserleuargglyargglyser
354045
thrleuglyleuaspilegluthralathrhisalaglylysglnile
505560
valgluglnileleuglulysgluseraspglualaleulysmetthr
65707580
ilealaservalproalaserargtyrleuthraspmetthrleuasp
859095
glumetserargasptrpphemetleumetprolysglnlysvalthr
100105110
glyserleucysileargmetaspglnalailemetasplysasnile
115120125
ileleulysalaasnpheservalilephegluargleugluthrleu
130135140
ileleuleuargalaphethrglugluglyalavalvalglygluile
145150155160
serproleuproserleuproglyhisthrasngluaspvallysasn
165170175
alaileglyvalleuileglyglyleulystrpasnaspasnthrval
180185190
argilesergluthrleuglnargphealatrpargserserhisglu
195200205
asnglyargproserpheproserlysglnlysarglysmetgluarg
210215220
thrilelysprogluile
225230
<210>55
<211>1497
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(1497)
<400>55
atggcgtctcaaggcaccaaacgatcctatgaacagatggaaactgat48
metalaserglnglythrlysargsertyrgluglnmetgluthrasp
151015
ggggaacgccagaatgcaactgaaatcagagcatctgtcggaaggatg96
glygluargglnasnalathrgluileargalaservalglyargmet
202530
gtgggaggaatcggacggttttatgtccagatgtgtactgagcttaaa144
valglyglyileglyargphetyrvalglnmetcysthrgluleulys
354045
ctaaacgaccatgaagggcggctgattcagaacagcataacaatagaa192
leuasnasphisgluglyargleuileglnasnserilethrileglu
505560
aggatggtgctttcggcattcgacgaaagaagaaacaagtatctcgag240
argmetvalleuseralapheaspgluargargasnlystyrleuglu
65707580
gagcatcccagtgctgggaaagaccctaagaaaacgggaggcccgata288
gluhisproseralaglylysaspprolyslysthrglyglyproile
859095
tacagaagaaaagatgggaaatggatgagggaactcatcctccatgat336
tyrargarglysaspglylystrpmetarggluleuileleuhisasp
100105110
aaagaagaaatcatgagaatctggcgtcaggccaacaatggtgaagac384
lysglugluilemetargiletrpargglnalaasnasnglygluasp
115120125
gctactgctggtcttactcatatgatgatctggcactccaatctcaat432
alathralaglyleuthrhismetmetiletrphisserasnleuasn
130135140
gacaccacataccaaagaacaagggctcttgttcggactgggatggat480
aspthrthrtyrglnargthrargalaleuvalargthrglymetasp
145150155160
cccagaatgtgctctctgatgcaaggctcaaccctcccacggagatct528
proargmetcysserleumetglnglyserthrleuproargargser
165170175
ggagccgctggtgctgcagtaaaaggcgttggaacaatggtaatggaa576
glyalaalaglyalaalavallysglyvalglythrmetvalmetglu
180185190
ctcatcagaatgatcaagcgcggaataaatgatcggaatttctggaga624
leuileargmetilelysargglyileasnaspargasnphetrparg
195200205
ggtgaaaatggtcgaagaaccagaattgcttatgaaagaatgtgcaat672
glygluasnglyargargthrargilealatyrgluargmetcysasn
210215220
atcctcaaagggaaatttcagacagcagcacaacgggctatgatggac720
ileleulysglylyspheglnthralaalaglnargalametmetasp
225230235240
caggtgagggaaggccgcaatcctggaaacgctgagattgaggatctc768
glnvalarggluglyargasnproglyasnalagluilegluaspleu
245250255
attttcttggcacgatcagcacttattttgagaggatcagtagcccat816
ilepheleualaargseralaleuileleuargglyservalalahis
260265270
aaatcatgcctacctgcctgtgtttatggccttgcagtaaccagtggg864
lyssercysleuproalacysvaltyrglyleualavalthrsergly
275280285
tatgactttgagaaggaaggatactctctggttggaattgatcctttc912
tyrasppheglulysgluglytyrserleuvalglyileaspprophe
290295300
aaactactccagaacagtcaaattttcagtctaatcagaccaaaagaa960
lysleuleuglnasnserglnilepheserleuileargprolysglu
305310315320
aacccagcacacaaaagccagttggtgtggatggcatgccattctgca1008
asnproalahislysserglnleuvaltrpmetalacyshisserala
325330335
gcatttgaggatctgagagttttaaatttcattagaggaaccaaagta1056
alaphegluaspleuargvalleuasnpheileargglythrlysval
340345350
atcccaagaggacagttaacaaccagaggagttcaaattgcttcaaat1104
ileproargglyglnleuthrthrargglyvalglnilealaserasn
355360365
gaaaacatggagacaataaattctagcacacttgaactgagaagcaaa1152
gluasnmetgluthrileasnserserthrleugluleuargserlys
370375380
tattgggcaataaggaccagaagcggaggaaacaccagtcaacagaga1200
tyrtrpalaileargthrargserglyglyasnthrserglnglnarg
385390395400
gcatctgcaggacagataagtgtgcaacctactttctcagtacagaga1248
alaseralaglyglnileservalglnprothrpheservalglnarg
405410415
aatcttccctttgagagagcaaccattatggctgcattcactggtaac1296
asnleuprophegluargalathrilemetalaalaphethrglyasn
420425430
actgaaggaaggacttccgacatgagaacggaaatcataaggatgatg1344
thrgluglyargthrseraspmetargthrgluileileargmetmet
435440445
gaaaatgccaaatcagaagatgtgtctttccaggggcggggagtcttc1392
gluasnalalyssergluaspvalserpheglnglyargglyvalphe
450455460
gagctctcggacgaaaaggcaacgaacccgatcgtgccttcctttgac1440
gluleuseraspglulysalathrasnproilevalproserpheasp
465470475480
atgagcaatgaagggtcttatttcttcggagacaatgctgaggagttt1488
metserasngluglysertyrphepheglyaspasnalaglugluphe
485490495
gacagttaa1497
aspser
<210>56
<211>498
<212>prt
<213>流感病毒
<400>56
metalaserglnglythrlysargsertyrgluglnmetgluthrasp
151015
glygluargglnasnalathrgluileargalaservalglyargmet
202530
valglyglyileglyargphetyrvalglnmetcysthrgluleulys
354045
leuasnasphisgluglyargleuileglnasnserilethrileglu
505560
argmetvalleuseralapheaspgluargargasnlystyrleuglu
65707580
gluhisproseralaglylysaspprolyslysthrglyglyproile
859095
tyrargarglysaspglylystrpmetarggluleuileleuhisasp
100105110
lysglugluilemetargiletrpargglnalaasnasnglygluasp
115120125
alathralaglyleuthrhismetmetiletrphisserasnleuasn
130135140
aspthrthrtyrglnargthrargalaleuvalargthrglymetasp
145150155160
proargmetcysserleumetglnglyserthrleuproargargser
165170175
glyalaalaglyalaalavallysglyvalglythrmetvalmetglu
180185190
leuileargmetilelysargglyileasnaspargasnphetrparg
195200205
glygluasnglyargargthrargilealatyrgluargmetcysasn
210215220
ileleulysglylyspheglnthralaalaglnargalametmetasp
225230235240
glnvalarggluglyargasnproglyasnalagluilegluaspleu
245250255
ilepheleualaargseralaleuileleuargglyservalalahis
260265270
lyssercysleuproalacysvaltyrglyleualavalthrsergly
275280285
tyrasppheglulysgluglytyrserleuvalglyileaspprophe
290295300
lysleuleuglnasnserglnilepheserleuileargprolysglu
305310315320
asnproalahislysserglnleuvaltrpmetalacyshisserala
325330335
alaphegluaspleuargvalleuasnpheileargglythrlysval
340345350
ileproargglyglnleuthrthrargglyvalglnilealaserasn
355360365
gluasnmetgluthrileasnserserthrleugluleuargserlys
370375380
tyrtrpalaileargthrargserglyglyasnthrserglnglnarg
385390395400
alaseralaglyglnileservalglnprothrpheservalglnarg
405410415
asnleuprophegluargalathrilemetalaalaphethrglyasn
420425430
thrgluglyargthrseraspmetargthrgluileileargmetmet
435440445
gluasnalalyssergluaspvalserpheglnglyargglyvalphe
450455460
gluleuseraspglulysalathrasnproilevalproserpheasp
465470475480
metserasngluglysertyrphepheglyaspasnalaglugluphe
485490495
aspser
<210>57
<211>1413
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(1413)
<400>57
atgaatccaaatcaaaagataatagcaattggatttgcatcattgggg48
metasnproasnglnlysileilealaileglyphealaserleugly
151015
atattaatcattaatgtcattctccatgtagtcagcattatagtaaca96
ileleuileileasnvalileleuhisvalvalserileilevalthr
202530
gtactggtcctcaataacaatagaacagatctgaactgcaaagggacg144
valleuvalleuasnasnasnargthraspleuasncyslysglythr
354045
atcataagagaatacaatgaaacagtaagagtagaaaaacttactcaa192
ileileargglutyrasngluthrvalargvalglulysleuthrgln
505560
tggtataataccagtacaattaagtacatagagagaccttcaaatgaa240
trptyrasnthrserthrilelystyrilegluargproserasnglu
65707580
tactacatgaataacactgaaccactttgtgaggcccaaggctttgca288
tyrtyrmetasnasnthrgluproleucysglualaglnglypheala
859095
ccattttccaaagataatggaatacgaattgggtcgagaggccatgtt336
propheserlysaspasnglyileargileglyserargglyhisval
100105110
tttgtgataagagaaccttttgtatcatgttcgccctcagaatgtaga384
phevalilearggluprophevalsercysserproserglucysarg
115120125
acctttttcctcacacagggctcattactcaatgacaaacattctaac432
thrphepheleuthrglnglyserleuleuasnasplyshisserasn
130135140
ggcacaataaaggatcgaagtccgtataggactttgatgagtgtcaaa480
glythrilelysaspargserprotyrargthrleumetservallys
145150155160
atagggcaatcacctaatgtatatcaagctaggtttgaatcggtggca528
ileglyglnserproasnvaltyrglnalaargphegluservalala
165170175
tggtcagcaacagcatgccatgatggaaaaaaatggatgacagttgga576
trpseralathralacyshisaspglylyslystrpmetthrvalgly
180185190
gtcacagggcccgacaatcaagcaattgcagtagtgaactatggaggt624
valthrglyproaspasnglnalailealavalvalasntyrglygly
195200205
gttccggttgatattattaattcatgggcaggggatattttaagaacc672
valprovalaspileileasnsertrpalaglyaspileleuargthr
210215220
caagaatcatcatgcacctgcattaaaggagactgttattgggtaatg720
glnglusersercysthrcysilelysglyaspcystyrtrpvalmet
225230235240
actgatggaccggcaaataggcaagctaaatataggatattcaaagca768
thraspglyproalaasnargglnalalystyrargilephelysala
245250255
aaagatggaagagtaattggacaaactgatataagtttcaatggggga816
lysaspglyargvalileglyglnthraspileserpheasnglygly
260265270
cacatagaggagtgttcttgttaccccaatgaagggaaggtggaatgc864
hisilegluglucyssercystyrproasngluglylysvalglucys
275280285
atatgcagggacaattggactggaacaaatagaccaattctggtaata912
ilecysargaspasntrpthrglythrasnargproileleuvalile
290295300
tcttctgatctatcgtacacagttggatatttgtgtgctggcattccc960
serseraspleusertyrthrvalglytyrleucysalaglyilepro
305310315320
actgacactcctaggggagaggatagtcaattcacaggctcatgtaca1008
thraspthrproargglygluaspserglnphethrglysercysthr
325330335
agtcctttgggaaataaaggatacggtgtaaaaggcttcgggtttcga1056
serproleuglyasnlysglytyrglyvallysglypheglyphearg
340345350
caaggaactgacgtatgggccggaaggacaattagtaggacttcaaga1104
glnglythraspvaltrpalaglyargthrileserargthrserarg
355360365
tcaggattcgaaataataaaaatcaggaatggttggacacagaacagt1152
serglyphegluileilelysileargasnglytrpthrglnasnser
370375380
aaggaccaaatcaggaggcaagtgattatcgatgacccaaattggtca1200
lysaspglnileargargglnvalileileaspaspproasntrpser
385390395400
ggatatagcggttctttcacattgccggttgaactgacaaaaaaggga1248
glytyrserglyserphethrleuprovalgluleuthrlyslysgly
405410415
tgtttggtcccctgtttctgggttgaaatgattagaggtaaacctgaa1296
cysleuvalprocysphetrpvalglumetileargglylysproglu
420425430
gaaacaacaatatggacctctagcagctccattgtgatgtgtggagta1344
gluthrthriletrpthrserserserserilevalmetcysglyval
435440445
gatcataaaattgccagttggtcatggcacgatggagctattcttccc1392
asphislysilealasertrpsertrphisaspglyalaileleupro
450455460
tttgacatcgataagatgtaa1413
pheaspileasplysmet
465470
<210>58
<211>470
<212>prt
<213>流感病毒
<400>58
metasnproasnglnlysileilealaileglyphealaserleugly
151015
ileleuileileasnvalileleuhisvalvalserileilevalthr
202530
valleuvalleuasnasnasnargthraspleuasncyslysglythr
354045
ileileargglutyrasngluthrvalargvalglulysleuthrgln
505560
trptyrasnthrserthrilelystyrilegluargproserasnglu
65707580
tyrtyrmetasnasnthrgluproleucysglualaglnglypheala
859095
propheserlysaspasnglyileargileglyserargglyhisval
100105110
phevalilearggluprophevalsercysserproserglucysarg
115120125
thrphepheleuthrglnglyserleuleuasnasplyshisserasn
130135140
glythrilelysaspargserprotyrargthrleumetservallys
145150155160
ileglyglnserproasnvaltyrglnalaargphegluservalala
165170175
trpseralathralacyshisaspglylyslystrpmetthrvalgly
180185190
valthrglyproaspasnglnalailealavalvalasntyrglygly
195200205
valprovalaspileileasnsertrpalaglyaspileleuargthr
210215220
glnglusersercysthrcysilelysglyaspcystyrtrpvalmet
225230235240
thraspglyproalaasnargglnalalystyrargilephelysala
245250255
lysaspglyargvalileglyglnthraspileserpheasnglygly
260265270
hisilegluglucyssercystyrproasngluglylysvalglucys
275280285
ilecysargaspasntrpthrglythrasnargproileleuvalile
290295300
serseraspleusertyrthrvalglytyrleucysalaglyilepro
305310315320
thraspthrproargglygluaspserglnphethrglysercysthr
325330335
serproleuglyasnlysglytyrglyvallysglypheglyphearg
340345350
glnglythraspvaltrpalaglyargthrileserargthrserarg
355360365
serglyphegluileilelysileargasnglytrpthrglnasnser
370375380
lysaspglnileargargglnvalileileaspaspproasntrpser
385390395400
glytyrserglyserphethrleuprovalgluleuthrlyslysgly
405410415
cysleuvalprocysphetrpvalglumetileargglylysproglu
420425430
gluthrthriletrpthrserserserserilevalmetcysglyval
435440445
asphislysilealasertrpsertrphisaspglyalaileleupro
450455460
pheaspileasplysmet
465470
<210>59
<211>981
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(756)
<400>59
atgagtcttctaaccgaggtcgaaacgtacgttctctctatcgtacca48
metserleuleuthrgluvalgluthrtyrvalleuserilevalpro
151015
tcaggccccctcaaagccgagatcgcgcagagacttgaagatgtcttt96
serglyproleulysalagluilealaglnargleugluaspvalphe
202530
gcgggaaagaacaccgatcttgaggcactcatggaatggctaaagaca144
alaglylysasnthraspleuglualaleumetglutrpleulysthr
354045
agaccaatcctgtcacctctgactaaagggattttaggatttgtattc192
argproileleuserproleuthrlysglyileleuglyphevalphe
505560
acgctcaccgtgcccagtgagcgaggactgcagcgtagacgctttgtc240
thrleuthrvalprosergluargglyleuglnargargargpheval
65707580
caaaatgcccttagtggaaacggagatccaaacaacatggacagagca288
glnasnalaleuserglyasnglyaspproasnasnmetaspargala
859095
gtaaaactgtacaggaagcttaaaagagaaataacattccatggggca336
vallysleutyrarglysleulysarggluilethrphehisglyala
100105110
aaagaggtggcactcagctattccactggtgcactagccagctgcatg384
lysgluvalalaleusertyrserthrglyalaleualasercysmet
115120125
ggactcatatacaacagaatgggaactgttacaaccgaagtggcattt432
glyleuiletyrasnargmetglythrvalthrthrgluvalalaphe
130135140
ggcctggtatgcgccacatgtgaacagattgctgattcccagcatcga480
glyleuvalcysalathrcysgluglnilealaaspserglnhisarg
145150155160
tctcacaggcagatggtgacaacaaccaacccattaatcagacatgaa528
serhisargglnmetvalthrthrthrasnproleuilearghisglu
165170175
aacagaatggtattagccagtaccacggctaaagccatggaacagatg576
asnargmetvalleualaserthrthralalysalametgluglnmet
180185190
gcaggatcgagtgagcaggcagcagaggccatggaggttgctagtagg624
alaglysersergluglnalaalaglualametgluvalalaserarg
195200205
gctaggcagatggtacaggcaatgagaaccattgggacccaccctagc672
alaargglnmetvalglnalametargthrileglythrhisproser
210215220
tccagtgccggtttgaaagatgatctccttgaaaatttacaggcctac720
serseralaglyleulysaspaspleuleugluasnleuglnalatyr
225230235240
cagaaacggatgggagtgcaaatgcagcgattcaagtgatcctctc766
glnlysargmetglyvalglnmetglnargphelys
245250
gtcattgcagcaagtatcattgggatcttgcacttgatattgtggattcttgatcgtctt826
ttcttcaaattcatttatcgtcgccttaaatacgggttgaaaagagggccttctacggaa886
ggagtacctgagtctatgagggaagaatatcggcaggaacagcagaatgctgtggatgtt946
gacgatggtcattttgtcaacatagagctggagta981
<210>60
<211>252
<212>prt
<213>流感病毒
<400>60
metserleuleuthrgluvalgluthrtyrvalleuserilevalpro
151015
serglyproleulysalagluilealaglnargleugluaspvalphe
202530
alaglylysasnthraspleuglualaleumetglutrpleulysthr
354045
argproileleuserproleuthrlysglyileleuglyphevalphe
505560
thrleuthrvalprosergluargglyleuglnargargargpheval
65707580
glnasnalaleuserglyasnglyaspproasnasnmetaspargala
859095
vallysleutyrarglysleulysarggluilethrphehisglyala
100105110
lysgluvalalaleusertyrserthrglyalaleualasercysmet
115120125
glyleuiletyrasnargmetglythrvalthrthrgluvalalaphe
130135140
glyleuvalcysalathrcysgluglnilealaaspserglnhisarg
145150155160
serhisargglnmetvalthrthrthrasnproleuilearghisglu
165170175
asnargmetvalleualaserthrthralalysalametgluglnmet
180185190
alaglysersergluglnalaalaglualametgluvalalaserarg
195200205
alaargglnmetvalglnalametargthrileglythrhisproser
210215220
serseralaglyleulysaspaspleuleugluasnleuglnalatyr
225230235240
glnlysargmetglyvalglnmetglnargphelys
245250
<210>61
<211>1698
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(1698)
<400>61
atgaagacaaccattattttaatactactgacccattgggcctacagt48
metlysthrthrileileleuileleuleuthrhistrpalatyrser
151015
caaaacccaatcagtggcaataacacagccacactgtgtctgggacac96
glnasnproileserglyasnasnthralathrleucysleuglyhis
202530
catgcagtagcaaatggaacattggtaaaaacaatgagtgatgatcaa144
hisalavalalaasnglythrleuvallysthrmetseraspaspgln
354045
attgaggtgacaaatgctacagaattagttcagagcatttcaatgggg192
ilegluvalthrasnalathrgluleuvalglnserilesermetgly
505560
aaaatatgcaacaaatcatatagaattctagatggaagaaattgcaca240
lysilecysasnlyssertyrargileleuaspglyargasncysthr
65707580
ttaatagatgcaatgctaggagacccccactgtgacgcctttcagtat288
leuileaspalametleuglyaspprohiscysaspalapheglntyr
859095
gagagttgggacctctttatagaaagaagcagcgctttcagcaattgc336
glusertrpaspleupheilegluargserseralapheserasncys
100105110
tacccatatgacatccctgactatgcatcgctccgatccattgtagca384
tyrprotyraspileproasptyralaserleuargserilevalala
115120125
tcctcagggacagtggaattcacagcagagggattcacatggacaggt432
serserglythrvalgluphethralagluglyphethrtrpthrgly
130135140
gtaactcaaaacggaagaagtggagcctgcaaaaggggatcagccgat480
valthrglnasnglyargserglyalacyslysargglyseralaasp
145150155160
agtttctttagccgactgaattggctaacaaaatctggaagctcttac528
serphepheserargleuasntrpleuthrlysserglysersertyr
165170175
cccacattgaatgtgacaatgcctaacaataaaaatttcgacaagcta576
prothrleuasnvalthrmetproasnasnlysasnpheasplysleu
180185190
tacatctgggggattcatcacccgagctcaaatcaagagcagacaaaa624
tyriletrpglyilehishisproserserasnglngluglnthrlys
195200205
ttgtacatccaagaatcaggacgagtaacagtctcaacaaaaagaagt672
leutyrileglngluserglyargvalthrvalserthrlysargser
210215220
caacaaacaataatccctaacatcggatctagaccgttggtcagaggt720
glnglnthrileileproasnileglyserargproleuvalarggly
225230235240
caatcaggcaggataagcatatactggaccattgtaaaacctggagat768
glnserglyargileseriletyrtrpthrilevallysproglyasp
245250255
atcctaatgataaacagtaatggcaacttagttgcaccgcggggatat816
ileleumetileasnserasnglyasnleuvalalaproargglytyr
260265270
tttaaattgaacacagggaaaagctctgtaatgagatccgatgtaccc864
phelysleuasnthrglylysserservalmetargseraspvalpro
275280285
atagacatttgtgtgtctgaatgtattacaccaaatggaagcatctcc912
ileaspilecysvalserglucysilethrproasnglyserileser
290295300
aacgacaagccattccaaaatgtgaacaaagttacatatggaaaatgc960
asnasplyspropheglnasnvalasnlysvalthrtyrglylyscys
305310315320
cccaagtatatcaggcaaaacactttaaagctggccactgggatgagg1008
prolystyrileargglnasnthrleulysleualathrglymetarg
325330335
aatgtaccagaaaagcaaaccagaggaatctttggagcaatagcggga1056
asnvalproglulysglnthrargglyilepheglyalailealagly
340345350
ttcatcgaaaacggctgggaaggaatggttgatgggtggtatgggttc1104
pheilegluasnglytrpgluglymetvalaspglytrptyrglyphe
355360365
cgatatcaaaactctgaaggaacagggcaagctgcagatctaaagagc1152
argtyrglnasnsergluglythrglyglnalaalaaspleulysser
370375380
actcaagcagccatcgaccagattaatggaaagttaaacagagtgatt1200
thrglnalaalaileaspglnileasnglylysleuasnargvalile
385390395400
gaaagaaccaatgagaaattccatcaaatagagaaggaattctcagaa1248
gluargthrasnglulysphehisglnileglulysglupheserglu
405410415
gtagaaggaagaattcaggacttggagaaatatgtagaagacaccaaa1296
valgluglyargileglnaspleuglulystyrvalgluaspthrlys
420425430
atagacctatggtcctacaatgcagaattgctggtggctctagaaaat1344
ileaspleutrpsertyrasnalagluleuleuvalalaleugluasn
435440445
caacatacaattgacttaacagatgcagaaatgaataaattatttgag1392
glnhisthrileaspleuthraspalaglumetasnlysleupheglu
450455460
aagactagacgccagttaagagaaaacgcagaagacatgggaggtgga1440
lysthrargargglnleuarggluasnalagluaspmetglyglygly
465470475480
tgtttcaagatttaccacaaatgtgataatgcatgcattgaatcaata1488
cysphelysiletyrhislyscysaspasnalacysilegluserile
485490495
agaactgggacatatgaccattacatatacaaagatgaagcattaaac1536
argthrglythrtyrasphistyriletyrlysaspglualaleuasn
500505510
aatcgatttcagatcaaaggtgtagagttgaaatcaggctacaaagat1584
asnargpheglnilelysglyvalgluleulysserglytyrlysasp
515520525
tggatactgtggatttcattcgccatatcatgcttcttaatttgcgtt1632
trpileleutrpileserphealailesercyspheleuilecysval
530535540
gttctattgggtttcattatgtgggcttgccaaaaaggcaacatcaga1680
valleuleuglypheilemettrpalacysglnlysglyasnilearg
545550555560
tgcaacatttgcatttga1698
cysasnilecysile
565
<210>62
<211>565
<212>prt
<213>流感病毒
<400>62
metlysthrthrileileleuileleuleuthrhistrpalatyrser
151015
glnasnproileserglyasnasnthralathrleucysleuglyhis
202530
hisalavalalaasnglythrleuvallysthrmetseraspaspgln
354045
ilegluvalthrasnalathrgluleuvalglnserilesermetgly
505560
lysilecysasnlyssertyrargileleuaspglyargasncysthr
65707580
leuileaspalametleuglyaspprohiscysaspalapheglntyr
859095
glusertrpaspleupheilegluargserseralapheserasncys
100105110
tyrprotyraspileproasptyralaserleuargserilevalala
115120125
serserglythrvalgluphethralagluglyphethrtrpthrgly
130135140
valthrglnasnglyargserglyalacyslysargglyseralaasp
145150155160
serphepheserargleuasntrpleuthrlysserglysersertyr
165170175
prothrleuasnvalthrmetproasnasnlysasnpheasplysleu
180185190
tyriletrpglyilehishisproserserasnglngluglnthrlys
195200205
leutyrileglngluserglyargvalthrvalserthrlysargser
210215220
glnglnthrileileproasnileglyserargproleuvalarggly
225230235240
glnserglyargileseriletyrtrpthrilevallysproglyasp
245250255
ileleumetileasnserasnglyasnleuvalalaproargglytyr
260265270
phelysleuasnthrglylysserservalmetargseraspvalpro
275280285
ileaspilecysvalserglucysilethrproasnglyserileser
290295300
asnasplyspropheglnasnvalasnlysvalthrtyrglylyscys
305310315320
prolystyrileargglnasnthrleulysleualathrglymetarg
325330335
asnvalproglulysglnthrargglyilepheglyalailealagly
340345350
pheilegluasnglytrpgluglymetvalaspglytrptyrglyphe
355360365
argtyrglnasnsergluglythrglyglnalaalaaspleulysser
370375380
thrglnalaalaileaspglnileasnglylysleuasnargvalile
385390395400
gluargthrasnglulysphehisglnileglulysglupheserglu
405410415
valgluglyargileglnaspleuglulystyrvalgluaspthrlys
420425430
ileaspleutrpsertyrasnalagluleuleuvalalaleugluasn
435440445
glnhisthrileaspleuthraspalaglumetasnlysleupheglu
450455460
lysthrargargglnleuarggluasnalagluaspmetglyglygly
465470475480
cysphelysiletyrhislyscysaspasnalacysilegluserile
485490495
argthrglythrtyrasphistyriletyrlysaspglualaleuasn
500505510
asnargpheglnilelysglyvalgluleulysserglytyrlysasp
515520525
trpileleutrpileserphealailesercyspheleuilecysval
530535540
valleuleuglypheilemettrpalacysglnlysglyasnilearg
545550555560
cysasnilecysile
565
<210>63
<211>2280
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(2280)
<400>63
atggagagaataaaagaactgagagatctgatgttacaatcccgcacc48
metgluargilelysgluleuargaspleumetleuglnserargthr
151015
cgcgagatactaacaaaaactactgtggaccacatggccataatcaag96
arggluileleuthrlysthrthrvalasphismetalaileilelys
202530
aaatacacatcaggaagacaagagaagaaccctgcacttaggatgaaa144
lystyrthrserglyargglnglulysasnproalaleuargmetlys
354045
tggatgatggcaatgaaatacccaattacagcagataagaggataatg192
trpmetmetalametlystyrproilethralaasplysargilemet
505560
gagatgattcctgagagaaatgaacagggacaaaccctttggagcaaa240
glumetileprogluargasngluglnglyglnthrleutrpserlys
65707580
acgaacgatgctggctcagaccgcgtaatggtatcacctctggcagtg288
thrasnaspalaglyseraspargvalmetvalserproleualaval
859095
acatggtggaataggaatggaccaacaacgaacacaattcattatcca336
thrtrptrpasnargasnglyprothrthrasnthrilehistyrpro
100105110
aaagtctacaaaacttattttgaaaaggttgaaagattgaaacacgga384
lysvaltyrlysthrtyrpheglulysvalgluargleulyshisgly
115120125
acctttggccccgttcattttaggaatcaagtcaagataagacgaaga432
thrpheglyprovalhispheargasnglnvallysileargargarg
130135140
gttgatgtaaaccctggtcacgcggacctcagtgctaaagaagcacaa480
valaspvalasnproglyhisalaaspleuseralalysglualagln
145150155160
gatgtgatcatggaagttgttttcccaaatgaagtgggagccagaatt528
aspvalilemetgluvalvalpheproasngluvalglyalaargile
165170175
ctaacatcagaatcacaactaacaataaccaaagagaaaaaggaagaa576
leuthrsergluserglnleuthrilethrlysglulyslysgluglu
180185190
cttcaggactgcaaaattgctcccttgatggtagcatacatgctagaa624
leuglnaspcyslysilealaproleumetvalalatyrmetleuglu
195200205
agagagttggtccgaaaaacaaggttcctcccagtagtaggcggaaca672
arggluleuvalarglysthrargpheleuprovalvalglyglythr
210215220
agcagtgtatacattgaagtgttgcatctgactcagggaacatgctgg720
serservaltyrilegluvalleuhisleuthrglnglythrcystrp
225230235240
gagcaaatgtacaccccaggaggaaaagttagaaacgatgatattgat768
gluglnmettyrthrproglyglylysvalargasnaspaspileasp
245250255
caaagtttaattattgcagcccggaacatagtgagaagagcaacagta816
glnserleuileilealaalaargasnilevalargargalathrval
260265270
tcagcagatccactagcatccctactggaaatgtgccacagtacacag864
seralaaspproleualaserleuleuglumetcyshisserthrgln
275280285
attggtggaacaaggatggtagacatccttaagcagaacccaacagag912
ileglyglythrargmetvalaspileleulysglnasnprothrglu
290295300
gaacaagctgtggatatatgcaaagcagcaatgggattgagaattagc960
gluglnalavalaspilecyslysalaalametglyleuargileser
305310315320
tcatcattcagctttggtggattcaccttcaaaaggacaagtggatca1008
serserpheserpheglyglyphethrphelysargthrserglyser
325330335
tcagtcaagagagaagaagaaatgcttacgggcaaccttcaaacattg1056
servallysargglugluglumetleuthrglyasnleuglnthrleu
340345350
aaaataagagtgcatgagggctatgaagaattcacaatggtcggaaga1104
lysileargvalhisgluglytyrglugluphethrmetvalglyarg
355360365
agagcaacagccattatcagaaaggcaaccagaagattgattcaattg1152
argalathralaileilearglysalathrargargleuileglnleu
370375380
atagtaagtgggagagatgaacaatcaattgctgaagcaataattgta1200
ilevalserglyargaspgluglnserilealaglualaileileval
385390395400
gccatggtgttttcgcaagaagattgcatgataaaagcagttcgaggc1248
alametvalpheserglngluaspcysmetilelysalavalarggly
405410415
gatttgaactttgttaatagagcaaatcagcgtttgaaccccatgcat1296
aspleuasnphevalasnargalaasnglnargleuasnpromethis
420425430
caactcttgaggcatttccaaaaagatgcaaaagtgcttttccaaaat1344
glnleuleuarghispheglnlysaspalalysvalleupheglnasn
435440445
tggggaattgaacccatcgacaatgtaatggggatgattggaatattg1392
trpglyilegluproileaspasnvalmetglymetileglyileleu
450455460
cctgacatgaccccaagcaccgagatgtcattgagaggagtgagagtc1440
proaspmetthrproserthrglumetserleuargglyvalargval
465470475480
agcaaaatgggagtggatgagtactccagcactgagagagtggtggtg1488
serlysmetglyvalaspglutyrserserthrgluargvalvalval
485490495
agcattgaccgttttttaagagttcgggatcaaaggggaaacatacta1536
serileaspargpheleuargvalargaspglnargglyasnileleu
500505510
ctgtcccctgaagaagtcagtgaaacacaaggaacggaaaagctgaca1584
leuserproglugluvalsergluthrglnglythrglulysleuthr
515520525
ataatttattcgtcatcaatgatgtgggagattaatggtcccgaatca1632
ileiletyrsersersermetmettrpgluileasnglyprogluser
530535540
gtgttggtcaatacttatcaatggatcatcagaaactgggaaattgta1680
valleuvalasnthrtyrglntrpileileargasntrpgluileval
545550555560
aaaattcagtggtcacaggaccccacaatgttatacaataagatagaa1728
lysileglntrpserglnaspprothrmetleutyrasnlysileglu
565570575
tttgaaccattccaatccctggtccctagggccaccagaagccaatac1776
pheglupropheglnserleuvalproargalathrargserglntyr
580585590
agcggtttcgtaagaaccctgtttcagcaaatgcgagatgtacttgga1824
serglyphevalargthrleupheglnglnmetargaspvalleugly
595600605
acatttgatactgctcaaataataaaactcctcccttttgccgctgct1872
thrpheaspthralaglnileilelysleuleuprophealaalaala
610615620
cctccggaacagagtaggatgcagttctcttctttgactgttaatgta1920
proprogluglnserargmetglnpheserserleuthrvalasnval
625630635640
agaggttcgggaatgaggatacttgtaagaggcaattccccagtgttc1968
argglyserglymetargileleuvalargglyasnserprovalphe
645650655
aactacaataaagtcactaaaaggctcacagtcctcggaaaggatgca2016
asntyrasnlysvalthrlysargleuthrvalleuglylysaspala
660665670
ggtgcgcttactgaggacccagatgaaggtacggctggagtagagtct2064
glyalaleuthrgluaspproaspgluglythralaglyvalgluser
675680685
gctgttctaagagggtttctcattttaggtaaagaaaacaagagatat2112
alavalleuargglypheleuileleuglylysgluasnlysargtyr
690695700
ggcccagcactaagcatcaatgaacttagcaaacttgcaaaaggggag2160
glyproalaleuserileasngluleuserlysleualalysglyglu
705710715720
aaagccaatgtactaattgggcaaggggacgtagtgttggtaatgaaa2208
lysalaasnvalleuileglyglnglyaspvalvalleuvalmetlys
725730735
cggaaacgtgactctagcatacttactgacagccagacagcgaccaaa2256
arglysargaspserserileleuthraspserglnthralathrlys
740745750
aggattcggatggccatcaattag2280
argileargmetalaileasn
755
<210>64
<211>759
<212>prt
<213>流感病毒
<400>64
metgluargilelysgluleuargaspleumetleuglnserargthr
151015
arggluileleuthrlysthrthrvalasphismetalaileilelys
202530
lystyrthrserglyargglnglulysasnproalaleuargmetlys
354045
trpmetmetalametlystyrproilethralaasplysargilemet
505560
glumetileprogluargasngluglnglyglnthrleutrpserlys
65707580
thrasnaspalaglyseraspargvalmetvalserproleualaval
859095
thrtrptrpasnargasnglyprothrthrasnthrilehistyrpro
100105110
lysvaltyrlysthrtyrpheglulysvalgluargleulyshisgly
115120125
thrpheglyprovalhispheargasnglnvallysileargargarg
130135140
valaspvalasnproglyhisalaaspleuseralalysglualagln
145150155160
aspvalilemetgluvalvalpheproasngluvalglyalaargile
165170175
leuthrsergluserglnleuthrilethrlysglulyslysgluglu
180185190
leuglnaspcyslysilealaproleumetvalalatyrmetleuglu
195200205
arggluleuvalarglysthrargpheleuprovalvalglyglythr
210215220
serservaltyrilegluvalleuhisleuthrglnglythrcystrp
225230235240
gluglnmettyrthrproglyglylysvalargasnaspaspileasp
245250255
glnserleuileilealaalaargasnilevalargargalathrval
260265270
seralaaspproleualaserleuleuglumetcyshisserthrgln
275280285
ileglyglythrargmetvalaspileleulysglnasnprothrglu
290295300
gluglnalavalaspilecyslysalaalametglyleuargileser
305310315320
serserpheserpheglyglyphethrphelysargthrserglyser
325330335
servallysargglugluglumetleuthrglyasnleuglnthrleu
340345350
lysileargvalhisgluglytyrglugluphethrmetvalglyarg
355360365
argalathralaileilearglysalathrargargleuileglnleu
370375380
ilevalserglyargaspgluglnserilealaglualaileileval
385390395400
alametvalpheserglngluaspcysmetilelysalavalarggly
405410415
aspleuasnphevalasnargalaasnglnargleuasnpromethis
420425430
glnleuleuarghispheglnlysaspalalysvalleupheglnasn
435440445
trpglyilegluproileaspasnvalmetglymetileglyileleu
450455460
proaspmetthrproserthrglumetserleuargglyvalargval
465470475480
serlysmetglyvalaspglutyrserserthrgluargvalvalval
485490495
serileaspargpheleuargvalargaspglnargglyasnileleu
500505510
leuserproglugluvalsergluthrglnglythrglulysleuthr
515520525
ileiletyrsersersermetmettrpgluileasnglyprogluser
530535540
valleuvalasnthrtyrglntrpileileargasntrpgluileval
545550555560
lysileglntrpserglnaspprothrmetleutyrasnlysileglu
565570575
pheglupropheglnserleuvalproargalathrargserglntyr
580585590
serglyphevalargthrleupheglnglnmetargaspvalleugly
595600605
thrpheaspthralaglnileilelysleuleuprophealaalaala
610615620
proprogluglnserargmetglnpheserserleuthrvalasnval
625630635640
argglyserglymetargileleuvalargglyasnserprovalphe
645650655
asntyrasnlysvalthrlysargleuthrvalleuglylysaspala
660665670
glyalaleuthrgluaspproaspgluglythralaglyvalgluser
675680685
alavalleuargglypheleuileleuglylysgluasnlysargtyr
690695700
glyproalaleuserileasngluleuserlysleualalysglyglu
705710715720
lysalaasnvalleuileglyglnglyaspvalvalleuvalmetlys
725730735
arglysargaspserserileleuthraspserglnthralathrlys
740745750
argileargmetalaileasn
755
<210>65
<211>2274
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(2274)
<400>65
atggatgtcaatccgactctacttttcttaaaggtgccagcgcaaaat48
metaspvalasnprothrleuleupheleulysvalproalaglnasn
151015
gctataagcacaacattcccttatactggagatcctccctacagtcat96
alaileserthrthrpheprotyrthrglyaspproprotyrserhis
202530
ggaacagggacaggatacaccatggatactgtcaacagaacacaccaa144
glythrglythrglytyrthrmetaspthrvalasnargthrhisgln
354045
tattcagaaaaagggaaatggacaacaaacactgagattggagcacca192
tyrserglulysglylystrpthrthrasnthrgluileglyalapro
505560
caacttaatccaatcgatggaccacttcctgaagacaatgaaccaagt240
glnleuasnproileaspglyproleuprogluaspasngluproser
65707580
gggtacgcccaaacagattgtgtattggaagcaatggctttccttgaa288
glytyralaglnthraspcysvalleuglualametalapheleuglu
859095
gaatcccatcccggaatctttgaaaattcgtgtcttgaaacgatggag336
gluserhisproglyilephegluasnsercysleugluthrmetglu
100105110
gtgattcagcagacaagagtggacaaactaacacaaggccgacaaact384
valileglnglnthrargvalasplysleuthrglnglyargglnthr
115120125
tatgattggaccttgaataggaatcaacctgccgcaacagcacttgct432
tyrasptrpthrleuasnargasnglnproalaalathralaleuala
130135140
aatacgattgaagtattcagatcaaatggtctgacctccaatgaatcg480
asnthrilegluvalpheargserasnglyleuthrserasngluser
145150155160
gggagattgatggacttcctcaaagatgtcatggagtccatgaacaag528
glyargleumetasppheleulysaspvalmetglusermetasnlys
165170175
gaggaaatggaaataacaacacacttccaacggaagagaagagtaaga576
gluglumetgluilethrthrhispheglnarglysargargvalarg
180185190
gacaacatgacaaagagaatgataacacagagaaccataggaaagaaa624
aspasnmetthrlysargmetilethrglnargthrileglylyslys
195200205
aaacaacgattaagcagaaagagctatctaatcagaacattaacccta672
lysglnargleuserarglyssertyrleuileargthrleuthrleu
210215220
aacacaatgaccaaggacgctgagagagggaaattgaaacgacgagca720
asnthrmetthrlysaspalagluargglylysleulysargargala
225230235240
atcgctaccccagggatgcagataagaggatttgtatattttgttgaa768
ilealathrproglymetglnileargglyphevaltyrphevalglu
245250255
acactagctcgaagaatatgtgaaaagcttgaacaatcaggattgcca816
thrleualaargargilecysglulysleugluglnserglyleupro
260265270
gttggcggtaatgagaaaaaggccaaactggctaatgtcgtcagaaaa864
valglyglyasnglulyslysalalysleualaasnvalvalarglys
275280285
atgatgactaattcccaagacactgaactctccttcaccatcactggg912
metmetthrasnserglnaspthrgluleuserphethrilethrgly
290295300
gacaataccaaatggaatgaaaatcagaacccacgcatattcctggca960
aspasnthrlystrpasngluasnglnasnproargilepheleuala
305310315320
atgatcacatacataactagagatcagccagaatggttcagaaatgtt1008
metilethrtyrilethrargaspglnproglutrppheargasnval
325330335
ctaagcattgcaccgattatgttctcaaataaaatggcaagactgggg1056
leuserilealaproilemetpheserasnlysmetalaargleugly
340345350
aaaggatatatgtttgaaagcaaaagtatgaaattgagaactcaaata1104
lysglytyrmetphegluserlyssermetlysleuargthrglnile
355360365
ccagcagaaatgctagcaagcattgacctaaaatatttcaatgattca1152
proalaglumetleualaserileaspleulystyrpheasnaspser
370375380
acaaaaaagaaaattgaaaagatacgaccactcctggttgacgggact1200
thrlyslyslysileglulysileargproleuleuvalaspglythr
385390395400
gcttcactgagtcctggcatgatgatgggaatgttcaacatgttgagc1248
alaserleuserproglymetmetmetglymetpheasnmetleuser
405410415
actgtgctgggtgtatccatattaaacctgggccagaggaaatataca1296
thrvalleuglyvalserileleuasnleuglyglnarglystyrthr
420425430
aagaccacatactggtgggatggtctgcaatcatccgatgactttgct1344
lysthrthrtyrtrptrpaspglyleuglnserseraspasppheala
435440445
ttgatagtgaatgcgcctaatcatgaaggaatacaagctggagtagac1392
leuilevalasnalaproasnhisgluglyileglnalaglyvalasp
450455460
agattctatagaacttgcaaactggtcgggatcaacatgagcaaaaag1440
argphetyrargthrcyslysleuvalglyileasnmetserlyslys
465470475480
aagtcctacataaatagaactggaacattcgaattcacaagctttttc1488
lyssertyrileasnargthrglythrphegluphethrserphephe
485490495
taccggtatggttttgtagccaatttcagcatggaactacccagtttt1536
tyrargtyrglyphevalalaasnphesermetgluleuproserphe
500505510
ggggtttccggaataaatgaatctgcagacatgagcattggagtgaca1584
glyvalserglyileasngluseralaaspmetserileglyvalthr
515520525
gtcatcaaaaacaacatgataaataatgatctcggtcctgccacggca1632
valilelysasnasnmetileasnasnaspleuglyproalathrala
530535540
caaatggcactccaactcttcattaaggattatcggtacacataccgg1680
glnmetalaleuglnleupheilelysasptyrargtyrthrtyrarg
545550555560
tgccatagaggtgatacccagatacaaaccagaagatcttttgagttg1728
cyshisargglyaspthrglnileglnthrargargserphegluleu
565570575
aagaaactgtgggaacagactcgatcaaagactggtctactggtatca1776
lyslysleutrpgluglnthrargserlysthrglyleuleuvalser
580585590
gatgggggtccaaacctatataacatcagaaacctacacatcccggaa1824
aspglyglyproasnleutyrasnileargasnleuhisileproglu
595600605
gtctgtttaaaatgggagctaatggatgaagattataaggggaggcta1872
valcysleulystrpgluleumetaspgluasptyrlysglyargleu
610615620
tgcaatccattgaatcctttcgttagtcacaaagaaattgaatcagtc1920
cysasnproleuasnprophevalserhislysgluilegluserval
625630635640
aacagtgcagtagtaatgcctgctcatggccctgccaaaagcatggag1968
asnseralavalvalmetproalahisglyproalalyssermetglu
645650655
tatgatgctgttgcaacaacacattcttggatccccaagaggaaccgg2016
tyraspalavalalathrthrhissertrpileprolysargasnarg
660665670
tccatattgaacacaagccaaaggggaatactagaagatgagcagatg2064
serileleuasnthrserglnargglyileleugluaspgluglnmet
675680685
tatcagaaatgctgcaacctgtttgaaaaattcttccccagcagctca2112
tyrglnlyscyscysasnleupheglulysphepheproserserser
690695700
tacagaagaccagtcggaatttctagtatggttgaggccatggtatcc2160
tyrargargprovalglyilesersermetvalglualametvalser
705710715720
agggcccgcattgatgcacgaattgacttcgaatctggacggataaag2208
argalaargileaspalaargileaspphegluserglyargilelys
725730735
aaggatgagttcgctgagatcatgaagatctgttccaccattgaagag2256
lysaspgluphealagluilemetlysilecysserthrilegluglu
740745750
ctcagacggcaaaaatag2274
leuargargglnlys
755
<210>66
<211>757
<212>prt
<213>流感病毒
<400>66
metaspvalasnprothrleuleupheleulysvalproalaglnasn
151015
alaileserthrthrpheprotyrthrglyaspproprotyrserhis
202530
glythrglythrglytyrthrmetaspthrvalasnargthrhisgln
354045
tyrserglulysglylystrpthrthrasnthrgluileglyalapro
505560
glnleuasnproileaspglyproleuprogluaspasngluproser
65707580
glytyralaglnthraspcysvalleuglualametalapheleuglu
859095
gluserhisproglyilephegluasnsercysleugluthrmetglu
100105110
valileglnglnthrargvalasplysleuthrglnglyargglnthr
115120125
tyrasptrpthrleuasnargasnglnproalaalathralaleuala
130135140
asnthrilegluvalpheargserasnglyleuthrserasngluser
145150155160
glyargleumetasppheleulysaspvalmetglusermetasnlys
165170175
gluglumetgluilethrthrhispheglnarglysargargvalarg
180185190
aspasnmetthrlysargmetilethrglnargthrileglylyslys
195200205
lysglnargleuserarglyssertyrleuileargthrleuthrleu
210215220
asnthrmetthrlysaspalagluargglylysleulysargargala
225230235240
ilealathrproglymetglnileargglyphevaltyrphevalglu
245250255
thrleualaargargilecysglulysleugluglnserglyleupro
260265270
valglyglyasnglulyslysalalysleualaasnvalvalarglys
275280285
metmetthrasnserglnaspthrgluleuserphethrilethrgly
290295300
aspasnthrlystrpasngluasnglnasnproargilepheleuala
305310315320
metilethrtyrilethrargaspglnproglutrppheargasnval
325330335
leuserilealaproilemetpheserasnlysmetalaargleugly
340345350
lysglytyrmetphegluserlyssermetlysleuargthrglnile
355360365
proalaglumetleualaserileaspleulystyrpheasnaspser
370375380
thrlyslyslysileglulysileargproleuleuvalaspglythr
385390395400
alaserleuserproglymetmetmetglymetpheasnmetleuser
405410415
thrvalleuglyvalserileleuasnleuglyglnarglystyrthr
420425430
lysthrthrtyrtrptrpaspglyleuglnserseraspasppheala
435440445
leuilevalasnalaproasnhisgluglyileglnalaglyvalasp
450455460
argphetyrargthrcyslysleuvalglyileasnmetserlyslys
465470475480
lyssertyrileasnargthrglythrphegluphethrserphephe
485490495
tyrargtyrglyphevalalaasnphesermetgluleuproserphe
500505510
glyvalserglyileasngluseralaaspmetserileglyvalthr
515520525
valilelysasnasnmetileasnasnaspleuglyproalathrala
530535540
glnmetalaleuglnleupheilelysasptyrargtyrthrtyrarg
545550555560
cyshisargglyaspthrglnileglnthrargargserphegluleu
565570575
lyslysleutrpgluglnthrargserlysthrglyleuleuvalser
580585590
aspglyglyproasnleutyrasnileargasnleuhisileproglu
595600605
valcysleulystrpgluleumetaspgluasptyrlysglyargleu
610615620
cysasnproleuasnprophevalserhislysgluilegluserval
625630635640
asnseralavalvalmetproalahisglyproalalyssermetglu
645650655
tyraspalavalalathrthrhissertrpileprolysargasnarg
660665670
serileleuasnthrserglnargglyileleugluaspgluglnmet
675680685
tyrglnlyscyscysasnleupheglulysphepheproserserser
690695700
tyrargargprovalglyilesersermetvalglualametvalser
705710715720
argalaargileaspalaargileaspphegluserglyargilelys
725730735
lysaspgluphealagluilemetlysilecysserthrilegluglu
740745750
leuargargglnlys
755
<210>67
<211>2151
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(2151)
<400>67
atggaagactttgtgcgacagtgcttcaatccaatgatcgtcgagctt48
metgluaspphevalargglncyspheasnprometilevalgluleu
151015
gcggaaaaggcaatgaaagaatatggagagaacccgaaaatcgaaaca96
alaglulysalametlysglutyrglygluasnprolysilegluthr
202530
aacaaatttgcagcaatatgcactcacttggaagtctgcttcatgtac144
asnlysphealaalailecysthrhisleugluvalcysphemettyr
354045
tcggatttccactttataaatgaactgggtgagtcagtggtcatagag192
seraspphehispheileasngluleuglygluservalvalileglu
505560
tctggtgacccaaatgctcttttgaaacacagatttgaaatcattgag240
serglyaspproasnalaleuleulyshisargphegluileileglu
65707580
gggagagatcgaacaatggcatggacagtagtaaacagcatctgcaac288
glyargaspargthrmetalatrpthrvalvalasnserilecysasn
859095
accacaagagctgaaaaacctaaatttcttccagatttatacgactat336
thrthrargalaglulysprolyspheleuproaspleutyrasptyr
100105110
aaagagaacagatttgttgaaattggtgtgacaaggagagaagttcac384
lysgluasnargphevalgluileglyvalthrargarggluvalhis
115120125
atatactacctggagaaggccaacaaaataaagtctgagaaaacacat432
iletyrtyrleuglulysalaasnlysilelysserglulysthrhis
130135140
atccacattttctcatttacaggagaagaaatggctacaaaagcggac480
ilehisilepheserphethrglygluglumetalathrlysalaasp
145150155160
tatactcttgatgaagagagtagagccaggatcaagaccagactattc528
tyrthrleuaspglugluserargalaargilelysthrargleuphe
165170175
actataagacaagaaatggccagtagaggcctctgggattcctttcgt576
thrileargglnglumetalaserargglyleutrpaspserphearg
180185190
cagtccgagagaggcgaagagacaattgaagaaagatttgaaatcaca624
glnsergluargglyglugluthrileglugluargphegluilethr
195200205
gggacgatgcgcaagcttgccaattacagtctcccaccgaacttctcc672
glythrmetarglysleualaasntyrserleuproproasnpheser
210215220
agccttgaaaattttagagtctatatagatggattcgaaccgaacggc720
serleugluasnpheargvaltyrileaspglyphegluproasngly
225230235240
tgcattgagagtaagctttctcaaatgtccaaagaagtaaatgccaaa768
cysilegluserlysleuserglnmetserlysgluvalasnalalys
245250255
atagaaccattttcaaagacaacaccccgaccactcaaaatgccaggt816
ileglupropheserlysthrthrproargproleulysmetprogly
260265270
ggtccaccctgccatcagcgatccaaattcttgctaatggatgctctg864
glyproprocyshisglnargserlyspheleuleumetaspalaleu
275280285
aaactgagcattgaggacccaagtcacgagggagaggggataccacta912
lysleuserilegluaspproserhisgluglygluglyileproleu
290295300
tatgatgcaatcaaatgcatgaaaactttctttggatggaaagagccc960
tyraspalailelyscysmetlysthrphepheglytrplysglupro
305310315320
agtattgttaaaccacataaaaagggtataaacccgaactatctccaa1008
serilevallysprohislyslysglyileasnproasntyrleugln
325330335
acttggaagcaagtattagaagaaatacaagaccttgagaacgaagaa1056
thrtrplysglnvalleuglugluileglnaspleugluasngluglu
340345350
aggacccccaagaccaagaatatgaaaaaaacaagccaattgaaatgg1104
argthrprolysthrlysasnmetlyslysthrserglnleulystrp
355360365
gcactaggtgaaaatatggcaccagagaaagtggattttgaggattgt1152
alaleuglygluasnmetalaproglulysvalaspphegluaspcys
370375380
aaagacatcaatgatttaaaacaatatgacagtgatgagccagaagca1200
lysaspileasnaspleulysglntyraspseraspgluprogluala
385390395400
aggtctcttgcaagttggattcaaagtgagttcaacaaggcttgtgag1248
argserleualasertrpileglnserglupheasnlysalacysglu
405410415
ctgacagattcaagctggatagagctcgatgaaattggggaggatgtc1296
leuthraspsersertrpilegluleuaspgluileglygluaspval
420425430
gccccaatagaatacattgcgagcatgaggagaaattattttactgct1344
alaproileglutyrilealasermetargargasntyrphethrala
435440445
gagatttcccattgtagagcaacagaatatataatgaaaggagtgtac1392
gluileserhiscysargalathrglutyrilemetlysglyvaltyr
450455460
atcaacactgctctactcaatgcatcctgtgctgcgatggatgaattt1440
ileasnthralaleuleuasnalasercysalaalametaspgluphe
465470475480
caattaattccgatgataagtaaatgcaggaccaaagaagggagaagg1488
glnleuileprometileserlyscysargthrlysgluglyargarg
485490495
aaaacaaatttatatggattcataataaagggaaggtcccatttaaga1536
lysthrasnleutyrglypheileilelysglyargserhisleuarg
500505510
aatgatactgacgtggtgaactttgtaagtatggaattttctctcact1584
asnaspthraspvalvalasnphevalsermetglupheserleuthr
515520525
gatccaagatttgagccacacaaatgggaaaaatactgcgttctagaa1632
aspproargphegluprohislystrpglulystyrcysvalleuglu
530535540
attggagacatgcttttaagaactgctgtaggtcaagtgtcaagaccc1680
ileglyaspmetleuleuargthralavalglyglnvalserargpro
545550555560
atgtttttgtatgtaaggacaaatggaacctctaaaattaaaatgaaa1728
metpheleutyrvalargthrasnglythrserlysilelysmetlys
565570575
tggggaatggaaatgaggcgctgcctccttcagtctctgcaacagatt1776
trpglymetglumetargargcysleuleuglnserleuglnglnile
580585590
gaaagcatgatcgaagctgagtcctcagtcaaagaaaaggacatgacc1824
glusermetileglualagluserservallysglulysaspmetthr
595600605
aaagaattttttgagaacaaatcagagacatggcctataggagagtcc1872
lysgluphephegluasnlyssergluthrtrpproileglygluser
610615620
cccaaaggagtggaagagggctcaatcgggaaggtttgcaggacctta1920
prolysglyvalglugluglyserileglylysvalcysargthrleu
625630635640
ttagcaaaatctgtgtttaacagtttatatgcatctccacaactggaa1968
leualalysservalpheasnserleutyralaserproglnleuglu
645650655
ggattttcagctgaatctaggaaattacttctcattgttcaggctctt2016
glypheseralagluserarglysleuleuleuilevalglnalaleu
660665670
agagatgacctggaacctggaacctttgatattggggggttatatgaa2064
argaspaspleugluproglythrpheaspileglyglyleutyrglu
675680685
tcaattgaggagtgcctgattaatgatccctgggttttgcttaatgca2112
serilegluglucysleuileasnaspprotrpvalleuleuasnala
690695700
tcttggttcaactccttcctcacacatgcactgaagtag2151
sertrppheasnserpheleuthrhisalaleulys
705710715
<210>68
<211>716
<212>prt
<213>流感病毒
<400>68
metgluaspphevalargglncyspheasnprometilevalgluleu
151015
alaglulysalametlysglutyrglygluasnprolysilegluthr
202530
asnlysphealaalailecysthrhisleugluvalcysphemettyr
354045
seraspphehispheileasngluleuglygluservalvalileglu
505560
serglyaspproasnalaleuleulyshisargphegluileileglu
65707580
glyargaspargthrmetalatrpthrvalvalasnserilecysasn
859095
thrthrargalaglulysprolyspheleuproaspleutyrasptyr
100105110
lysgluasnargphevalgluileglyvalthrargarggluvalhis
115120125
iletyrtyrleuglulysalaasnlysilelysserglulysthrhis
130135140
ilehisilepheserphethrglygluglumetalathrlysalaasp
145150155160
tyrthrleuaspglugluserargalaargilelysthrargleuphe
165170175
thrileargglnglumetalaserargglyleutrpaspserphearg
180185190
glnsergluargglyglugluthrileglugluargphegluilethr
195200205
glythrmetarglysleualaasntyrserleuproproasnpheser
210215220
serleugluasnpheargvaltyrileaspglyphegluproasngly
225230235240
cysilegluserlysleuserglnmetserlysgluvalasnalalys
245250255
ileglupropheserlysthrthrproargproleulysmetprogly
260265270
glyproprocyshisglnargserlyspheleuleumetaspalaleu
275280285
lysleuserilegluaspproserhisgluglygluglyileproleu
290295300
tyraspalailelyscysmetlysthrphepheglytrplysglupro
305310315320
serilevallysprohislyslysglyileasnproasntyrleugln
325330335
thrtrplysglnvalleuglugluileglnaspleugluasngluglu
340345350
argthrprolysthrlysasnmetlyslysthrserglnleulystrp
355360365
alaleuglygluasnmetalaproglulysvalaspphegluaspcys
370375380
lysaspileasnaspleulysglntyraspseraspgluprogluala
385390395400
argserleualasertrpileglnserglupheasnlysalacysglu
405410415
leuthraspsersertrpilegluleuaspgluileglygluaspval
420425430
alaproileglutyrilealasermetargargasntyrphethrala
435440445
gluileserhiscysargalathrglutyrilemetlysglyvaltyr
450455460
ileasnthralaleuleuasnalasercysalaalametaspgluphe
465470475480
glnleuileprometileserlyscysargthrlysgluglyargarg
485490495
lysthrasnleutyrglypheileilelysglyargserhisleuarg
500505510
asnaspthraspvalvalasnphevalsermetglupheserleuthr
515520525
aspproargphegluprohislystrpglulystyrcysvalleuglu
530535540
ileglyaspmetleuleuargthralavalglyglnvalserargpro
545550555560
metpheleutyrvalargthrasnglythrserlysilelysmetlys
565570575
trpglymetglumetargargcysleuleuglnserleuglnglnile
580585590
glusermetileglualagluserservallysglulysaspmetthr
595600605
lysgluphephegluasnlyssergluthrtrpproileglygluser
610615620
prolysglyvalglugluglyserileglylysvalcysargthrleu
625630635640
leualalysservalpheasnserleutyralaserproglnleuglu
645650655
glypheseralagluserarglysleuleuleuilevalglnalaleu
660665670
argaspaspleugluproglythrpheaspileglyglyleutyrglu
675680685
serilegluglucysleuileasnaspprotrpvalleuleuasnala
690695700
sertrppheasnserpheleuthrhisalaleulys
705710715
<210>69
<211>844
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(690)
<400>69
atggattccaacactgtgtcaagctttcaggtagactgttttctttgg48
metaspserasnthrvalserserpheglnvalaspcyspheleutrp
151015
catgtccgtaaacgattcgcagaccaagaactgggtgatgccccattc96
hisvalarglysargphealaaspglngluleuglyaspalaprophe
202530
cttgaccggcttcgccgagaccagaagtccctaaggggaagaggtagc144
leuaspargleuargargaspglnlysserleuargglyargglyser
354045
actcttggtctggacatcgaaacagccactcatgcaggaaagcagata192
thrleuglyleuaspilegluthralathrhisalaglylysglnile
505560
gtggagcagattctggaaaaggaatcagatgaggcacttaaaatgacc240
valgluglnileleuglulysgluseraspglualaleulysmetthr
65707580
attgcctctgttcctgcttcacgctacttaactgacatgactcttgat288
ilealaservalproalaserargtyrleuthraspmetthrleuasp
859095
gagatgtcaagagactggttcatgctcatgcccaagcaaaaagtaaca336
glumetserargasptrpphemetleumetprolysglnlysvalthr
100105110
ggctccctatgtataagaatggaccaggcaatcatggataagaacatc384
glyserleucysileargmetaspglnalailemetasplysasnile
115120125
atacttaaagcaaactttagtgtgattttcgaaaggctggaaacacta432
ileleulysalaasnpheservalilephegluargleugluthrleu
130135140
atactacttagagccttcaccgaagaaggagcagtcgttggcgaaatt480
ileleuleuargalaphethrglugluglyalavalvalglygluile
145150155160
tcaccattaccttctcttccaggacatactaatgaggatgtcaaaaat528
serproleuproserleuproglyhisthrasngluaspvallysasn
165170175
gcaattggggtcctcatcggaggacttaaatggaatgataatacggtt576
alaileglyvalleuileglyglyleulystrpasnaspasnthrval
180185190
agaatctctgaaactctacagagattcgcttggagaagcagtcatgaa624
argilesergluthrleuglnargphealatrpargserserhisglu
195200205
aatgggagaccttcattcccttcaaaacagaaacgaaaaatggagaga672
asnglyargproserpheproserlysglnlysarglysmetgluarg
210215220
acaattaagccagaaatttgaagaaataagatggttgattgaagaagt720
thrilelysprogluile
225230
gcgacatagattgaaaaatacagaaaatagttttgaacaaataacatttatgcaagcctt780
acaactattgcttgaagtagaacaagagataagaactttctcgtttcagcttatttaatg840
ataa844
<210>70
<211>230
<212>prt
<213>流感病毒
<400>70
metaspserasnthrvalserserpheglnvalaspcyspheleutrp
151015
hisvalarglysargphealaaspglngluleuglyaspalaprophe
202530
leuaspargleuargargaspglnlysserleuargglyargglyser
354045
thrleuglyleuaspilegluthralathrhisalaglylysglnile
505560
valgluglnileleuglulysgluseraspglualaleulysmetthr
65707580
ilealaservalproalaserargtyrleuthraspmetthrleuasp
859095
glumetserargasptrpphemetleumetprolysglnlysvalthr
100105110
glyserleucysileargmetaspglnalailemetasplysasnile
115120125
ileleulysalaasnpheservalilephegluargleugluthrleu
130135140
ileleuleuargalaphethrglugluglyalavalvalglygluile
145150155160
serproleuproserleuproglyhisthrasngluaspvallysasn
165170175
alaileglyvalleuileglyglyleulystrpasnaspasnthrval
180185190
argilesergluthrleuglnargphealatrpargserserhisglu
195200205
asnglyargproserpheproserlysglnlysarglysmetgluarg
210215220
thrilelysprogluile
225230
<210>71
<211>1497
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(1497)
<400>71
atggcgtctcaaggcaccaaacgatcctatgaacagatggaaactgat48
metalaserglnglythrlysargsertyrgluglnmetgluthrasp
151015
ggggaacgccagaatgcaactgaaatcagagcatctgtcggaaggatg96
glygluargglnasnalathrgluileargalaservalglyargmet
202530
gtgggaggaatcggacggttttatgtccagatgtgtactgagcttaaa144
valglyglyileglyargphetyrvalglnmetcysthrgluleulys
354045
ctaaacgaccatgaagggcggctgattcagaacagcataacaatagaa192
leuasnasphisgluglyargleuileglnasnserilethrileglu
505560
aggatggtgctttcggcattcgacgaaagaagaaacaagtatctcgag240
argmetvalleuseralapheaspgluargargasnlystyrleuglu
65707580
gagcatcccagtgctgggaaagaccctaagaaaacgggaggcccgata288
gluhisproseralaglylysaspprolyslysthrglyglyproile
859095
tacagaagaaaagatgggaaatggatgagggaactcatcctccatgat336
tyrargarglysaspglylystrpmetarggluleuileleuhisasp
100105110
aaagaagaaatcatgagaatctggcgtcaggccaacaatggtgaagac384
lysglugluilemetargiletrpargglnalaasnasnglygluasp
115120125
gctactgctggtcttactcatatgatgatctggcactccaatctcaat432
alathralaglyleuthrhismetmetiletrphisserasnleuasn
130135140
gacaccacataccaaagaacaagggctcttgttcggactgggatggat480
aspthrthrtyrglnargthrargalaleuvalargthrglymetasp
145150155160
cccagaatgtgctctctgatgcaaggctcaaccctcccacggagatct528
proargmetcysserleumetglnglyserthrleuproargargser
165170175
ggagccgctggtgctgcagtaaaaggcgttggaacaatggtaatggaa576
glyalaalaglyalaalavallysglyvalglythrmetvalmetglu
180185190
ctcatcagaatgatcaagcgcggaataaatgatcggaatttctggaga624
leuileargmetilelysargglyileasnaspargasnphetrparg
195200205
ggtgaaaatggtcgaagaaccagaattgcttatgaaagaatgtgcaat672
glygluasnglyargargthrargilealatyrgluargmetcysasn
210215220
atcctcaaagggaaatttcagacagcagcacaacgggctatgatggac720
ileleulysglylyspheglnthralaalaglnargalametmetasp
225230235240
caggtgagggaaggccgcaatcctggaaacgctgagattgaggatctc768
glnvalarggluglyargasnproglyasnalagluilegluaspleu
245250255
attttcttggcacgatcagcacttattttgagaggatcagtagcccat816
ilepheleualaargseralaleuileleuargglyservalalahis
260265270
aaatcatgcctacctgcctgtgtttatggccttgcactaaccagtggg864
lyssercysleuproalacysvaltyrglyleualaleuthrsergly
275280285
tatgactttgagaaggaaggatactctctggttggaattgatcctttc912
tyrasppheglulysgluglytyrserleuvalglyileaspprophe
290295300
aaactactccagaacagtcaaattttcagtctaatcagaccaaaagaa960
lysleuleuglnasnserglnilepheserleuileargprolysglu
305310315320
aacccagcacacaaaagccagttggtgtggatggcatgccattctgca1008
asnproalahislysserglnleuvaltrpmetalacyshisserala
325330335
gcatttgaggatctgagagttttaaatttcattagaggaaccaaagta1056
alaphegluaspleuargvalleuasnpheileargglythrlysval
340345350
atcccaagaggacagttaacaaccagaggagttcaaattgcttcaaat1104
ileproargglyglnleuthrthrargglyvalglnilealaserasn
355360365
gaaaacatggagacaataaattctagcacacttgaactgagaagcaaa1152
gluasnmetgluthrileasnserserthrleugluleuargserlys
370375380
tattgggcaataaggaccagaagcggaggaaacaccagtcaacagaga1200
tyrtrpalaileargthrargserglyglyasnthrserglnglnarg
385390395400
gcatctgcaggacagataagtgtgcaacctactttctcagtacagaga1248
alaseralaglyglnileservalglnprothrpheservalglnarg
405410415
aatcttccctttgagagagcaaccattatggctgcattcactggtaac1296
asnleuprophegluargalathrilemetalaalaphethrglyasn
420425430
actgaaggaaggacttccgacatgagaacggaaatcataaggatgatg1344
thrgluglyargthrseraspmetargthrgluileileargmetmet
435440445
gaaaatgccaaatcagaagatgtgtctttccaggggcggggagtcttc1392
gluasnalalyssergluaspvalserpheglnglyargglyvalphe
450455460
gagctctcggacgaaaaggcaacgaacccgatcgtgccttcctttgac1440
gluleuseraspglulysalathrasnproilevalproserpheasp
465470475480
atgagcaatgaagggtcttatttcttcggagacaatgctgaggagttt1488
metserasngluglysertyrphepheglyaspasnalaglugluphe
485490495
gacagttaa1497
aspser
<210>72
<211>498
<212>prt
<213>流感病毒
<400>72
metalaserglnglythrlysargsertyrgluglnmetgluthrasp
151015
glygluargglnasnalathrgluileargalaservalglyargmet
202530
valglyglyileglyargphetyrvalglnmetcysthrgluleulys
354045
leuasnasphisgluglyargleuileglnasnserilethrileglu
505560
argmetvalleuseralapheaspgluargargasnlystyrleuglu
65707580
gluhisproseralaglylysaspprolyslysthrglyglyproile
859095
tyrargarglysaspglylystrpmetarggluleuileleuhisasp
100105110
lysglugluilemetargiletrpargglnalaasnasnglygluasp
115120125
alathralaglyleuthrhismetmetiletrphisserasnleuasn
130135140
aspthrthrtyrglnargthrargalaleuvalargthrglymetasp
145150155160
proargmetcysserleumetglnglyserthrleuproargargser
165170175
glyalaalaglyalaalavallysglyvalglythrmetvalmetglu
180185190
leuileargmetilelysargglyileasnaspargasnphetrparg
195200205
glygluasnglyargargthrargilealatyrgluargmetcysasn
210215220
ileleulysglylyspheglnthralaalaglnargalametmetasp
225230235240
glnvalarggluglyargasnproglyasnalagluilegluaspleu
245250255
ilepheleualaargseralaleuileleuargglyservalalahis
260265270
lyssercysleuproalacysvaltyrglyleualaleuthrsergly
275280285
tyrasppheglulysgluglytyrserleuvalglyileaspprophe
290295300
lysleuleuglnasnserglnilepheserleuileargprolysglu
305310315320
asnproalahislysserglnleuvaltrpmetalacyshisserala
325330335
alaphegluaspleuargvalleuasnpheileargglythrlysval
340345350
ileproargglyglnleuthrthrargglyvalglnilealaserasn
355360365
gluasnmetgluthrileasnserserthrleugluleuargserlys
370375380
tyrtrpalaileargthrargserglyglyasnthrserglnglnarg
385390395400
alaseralaglyglnileservalglnprothrpheservalglnarg
405410415
asnleuprophegluargalathrilemetalaalaphethrglyasn
420425430
thrgluglyargthrseraspmetargthrgluileileargmetmet
435440445
gluasnalalyssergluaspvalserpheglnglyargglyvalphe
450455460
gluleuseraspglulysalathrasnproilevalproserpheasp
465470475480
metserasngluglysertyrphepheglyaspasnalaglugluphe
485490495
aspser
<210>73
<211>1413
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(1413)
<400>73
atgaatccaaatcaaaagataatagcaattggatttgcatcattgggg48
metasnproasnglnlysileilealaileglyphealaserleugly
151015
atattaatcattaatgtcattctccatgtagtcagcattatagtaaca96
ileleuileileasnvalileleuhisvalvalserileilevalthr
202530
gtactggtcctcaataacaatagaacagatctgaactgcaaagggacg144
valleuvalleuasnasnasnargthraspleuasncyslysglythr
354045
atcataagagaatacaatgaaacagtaagagtagaaaaacttactcaa192
ileileargglutyrasngluthrvalargvalglulysleuthrgln
505560
tggtataataccagtacaattaagtacatagagagaccttcaaatgaa240
trptyrasnthrserthrilelystyrilegluargproserasnglu
65707580
tactacatgaataacactgaaccactttgtgaggcccaaggctttgca288
tyrtyrmetasnasnthrgluproleucysglualaglnglypheala
859095
ccattttccaaagataatggaatacgaattgggtcgagaggccatgtt336
propheserlysaspasnglyileargileglyserargglyhisval
100105110
tttgtgataagagaaccttttgtatcatgttcgccctcagaatgtaga384
phevalilearggluprophevalsercysserproserglucysarg
115120125
acctttttcctcacacagggctcattactcaatgacaaacattctaac432
thrphepheleuthrglnglyserleuleuasnasplyshisserasn
130135140
ggcacaataaaggatcgaagtccgtataggactttgatgagtgtcaaa480
glythrilelysaspargserprotyrargthrleumetservallys
145150155160
atagggcaatcacctaatgtatatcaagctaggtttgaatcggtggca528
ileglyglnserproasnvaltyrglnalaargphegluservalala
165170175
tggtcagcaacagcatgccatgatggaaaaaaatggatgacagttgga576
trpseralathralacyshisaspglylyslystrpmetthrvalgly
180185190
gtcacagggcccgacaatcaagcaattgcagtagtgaactatggaggt624
valthrglyproaspasnglnalailealavalvalasntyrglygly
195200205
gttccggttgatattattaattcatgggcaggggatattttaagaacc672
valprovalaspileileasnsertrpalaglyaspileleuargthr
210215220
caagaatcatcatgcacctgcattaaaggagactgttattgggtaatg720
glnglusersercysthrcysilelysglyaspcystyrtrpvalmet
225230235240
actgatggaccggcaaataggcaagctaaatataggatattcaaagca768
thraspglyproalaasnargglnalalystyrargilephelysala
245250255
aaagatggaagagtaattggacaaactgatataagtttcaatggggga816
lysaspglyargvalileglyglnthraspileserpheasnglygly
260265270
cacatagaggagtgttcttgttaccccaatgaagggaaggtggaatgc864
hisilegluglucyssercystyrproasngluglylysvalglucys
275280285
atatgcagggacaattggactggaacaaatagaccaattctggtaata912
ilecysargaspasntrpthrglythrasnargproileleuvalile
290295300
tcttctgatctatcgtacacagttggatatttgtgtgctggcattccc960
serseraspleusertyrthrvalglytyrleucysalaglyilepro
305310315320
actgacactcctaggggagaggatagtcaattcacaggctcatgtaca1008
thraspthrproargglygluaspserglnphethrglysercysthr
325330335
agtcctttgggaaataaaggatacggtgtaaaaggcttcgggtttcga1056
serproleuglyasnlysglytyrglyvallysglypheglyphearg
340345350
caaggaactgacgtatgggccggaaggacaattagtaggacttcaaga1104
glnglythraspvaltrpalaglyargthrileserargthrserarg
355360365
tcaggattcgaaataataaaaatcaggaatggttggacacagaacagt1152
serglyphegluileilelysileargasnglytrpthrglnasnser
370375380
aaggaccaaatcaggaggcaagtgattatcgatgacccaaattggtca1200
lysaspglnileargargglnvalileileaspaspproasntrpser
385390395400
ggatatagcggttctttcacattgccggttgaactgacaaaaaaggga1248
glytyrserglyserphethrleuprovalgluleuthrlyslysgly
405410415
tgtttggtcccctgtttctgggttgaaatgattagaggtaaacctgaa1296
cysleuvalprocysphetrpvalglumetileargglylysproglu
420425430
gaaacaacaatatggacctctagcagctccattgtgatgtgtggagta1344
gluthrthriletrpthrserserserserilevalmetcysglyval
435440445
gatcataaaattgccagttggtcatggcacgatggagctattcttccc1392
asphislysilealasertrpsertrphisaspglyalaileleupro
450455460
tttgacatcgataagatgtaa1413
pheaspileasplysmet
465470
<210>74
<211>470
<212>prt
<213>流感病毒
<400>74
metasnproasnglnlysileilealaileglyphealaserleugly
151015
ileleuileileasnvalileleuhisvalvalserileilevalthr
202530
valleuvalleuasnasnasnargthraspleuasncyslysglythr
354045
ileileargglutyrasngluthrvalargvalglulysleuthrgln
505560
trptyrasnthrserthrilelystyrilegluargproserasnglu
65707580
tyrtyrmetasnasnthrgluproleucysglualaglnglypheala
859095
propheserlysaspasnglyileargileglyserargglyhisval
100105110
phevalilearggluprophevalsercysserproserglucysarg
115120125
thrphepheleuthrglnglyserleuleuasnasplyshisserasn
130135140
glythrilelysaspargserprotyrargthrleumetservallys
145150155160
ileglyglnserproasnvaltyrglnalaargphegluservalala
165170175
trpseralathralacyshisaspglylyslystrpmetthrvalgly
180185190
valthrglyproaspasnglnalailealavalvalasntyrglygly
195200205
valprovalaspileileasnsertrpalaglyaspileleuargthr
210215220
glnglusersercysthrcysilelysglyaspcystyrtrpvalmet
225230235240
thraspglyproalaasnargglnalalystyrargilephelysala
245250255
lysaspglyargvalileglyglnthraspileserpheasnglygly
260265270
hisilegluglucyssercystyrproasngluglylysvalglucys
275280285
ilecysargaspasntrpthrglythrasnargproileleuvalile
290295300
serseraspleusertyrthrvalglytyrleucysalaglyilepro
305310315320
thraspthrproargglygluaspserglnphethrglysercysthr
325330335
serproleuglyasnlysglytyrglyvallysglypheglyphearg
340345350
glnglythraspvaltrpalaglyargthrileserargthrserarg
355360365
serglyphegluileilelysileargasnglytrpthrglnasnser
370375380
lysaspglnileargargglnvalileileaspaspproasntrpser
385390395400
glytyrserglyserphethrleuprovalgluleuthrlyslysgly
405410415
cysleuvalprocysphetrpvalglumetileargglylysproglu
420425430
gluthrthriletrpthrserserserserilevalmetcysglyval
435440445
asphislysilealasertrpsertrphisaspglyalaileleupro
450455460
pheaspileasplysmet
465470
<210>75
<211>981
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(756)
<400>75
atgagtcttctaaccgaggtcgaaacgtacgttctctctatcgtacca48
metserleuleuthrgluvalgluthrtyrvalleuserilevalpro
151015
tcaggccccctcaaagccgagatcgcgcagagacttgaagatgtcttt96
serglyproleulysalagluilealaglnargleugluaspvalphe
202530
gcgggaaagaacaccgatcttgaggcactcatggaatggctaaagaca144
alaglylysasnthraspleuglualaleumetglutrpleulysthr
354045
agaccaatcctgtcacctctgactaaagggattttaggatttgtattc192
argproileleuserproleuthrlysglyileleuglyphevalphe
505560
acgctcaccgtgcccagtgagcgaggactgcagcgtagacgctttgtc240
thrleuthrvalprosergluargglyleuglnargargargpheval
65707580
caaaatgcccttagtggaaacggagatccaaacaacatggacagagca288
glnasnalaleuserglyasnglyaspproasnasnmetaspargala
859095
gtaaaactgtacaggaagcttaaaagagaaataacattccatggggca336
vallysleutyrarglysleulysarggluilethrphehisglyala
100105110
aaagaggtggcactcagctattccactggtgcactagccagctgcatg384
lysgluvalalaleusertyrserthrglyalaleualasercysmet
115120125
ggactcatatacaacagaatgggaactgttacaaccgaagtggcattt432
glyleuiletyrasnargmetglythrvalthrthrgluvalalaphe
130135140
ggcctggtatgcgccacatgtgaacagattgctgattcccagcatcga480
glyleuvalcysalathrcysgluglnilealaaspserglnhisarg
145150155160
tctcacaggcagatggtgacaacaaccaacccattaatcagacatgaa528
serhisargglnmetvalthrthrthrasnproleuilearghisglu
165170175
aacagaatggtattagccagtaccacggctaaagccatggaacagatg576
asnargmetvalleualaserthrthralalysalametgluglnmet
180185190
gcaggatcgagtgagcaggcagcagaggccatggaggttgctagtagg624
alaglysersergluglnalaalaglualametgluvalalaserarg
195200205
gctaggcagatggtacaggcaatgagaaccattgggacccaccctagc672
alaargglnmetvalglnalametargthrileglythrhisproser
210215220
tccagtgccggtttgaaagatgatctccttgaaaatttacaggcctac720
serseralaglyleulysaspaspleuleugluasnleuglnalatyr
225230235240
cagaaacggatgggagtgcaaatgcagcgattcaagtgatcctctc766
glnlysargmetglyvalglnmetglnargphelys
245250
gtcattgcagcaagtatcattgggatcttgcacttgatattgtggattcttgatcgtctt826
ttcttcaaattcatttatcgtcgccttaaatacgggttgaaaagagggccttctacggaa886
ggagtacctgagtctatgagggaagaatatcggcaggaacagcagaatgctgtggatgtt946
gacgatggtcattttgtcaacatagagctggagta981
<210>76
<211>252
<212>prt
<213>流感病毒
<400>76
metserleuleuthrgluvalgluthrtyrvalleuserilevalpro
151015
serglyproleulysalagluilealaglnargleugluaspvalphe
202530
alaglylysasnthraspleuglualaleumetglutrpleulysthr
354045
argproileleuserproleuthrlysglyileleuglyphevalphe
505560
thrleuthrvalprosergluargglyleuglnargargargpheval
65707580
glnasnalaleuserglyasnglyaspproasnasnmetaspargala
859095
vallysleutyrarglysleulysarggluilethrphehisglyala
100105110
lysgluvalalaleusertyrserthrglyalaleualasercysmet
115120125
glyleuiletyrasnargmetglythrvalthrthrgluvalalaphe
130135140
glyleuvalcysalathrcysgluglnilealaaspserglnhisarg
145150155160
serhisargglnmetvalthrthrthrasnproleuilearghisglu
165170175
asnargmetvalleualaserthrthralalysalametgluglnmet
180185190
alaglysersergluglnalaalaglualametgluvalalaserarg
195200205
alaargglnmetvalglnalametargthrileglythrhisproser
210215220
serseralaglyleulysaspaspleuleugluasnleuglnalatyr
225230235240
glnlysargmetglyvalglnmetglnargphelys
245250
<210>77
<211>1698
<212>dna
<213>流感病毒
<220>
<221>cds
<222>(1)..(1698)
<400>77
atgaagacaaccattattttaatactactgacccattgggcctacagt48
metlysthrthrileileleuileleuleuthrhistrpalatyrser
151015
caaaacccaatcagtggcaataacacagccacactgtgtctgggacac96
glnasnproileserglyasnasnthralathrleucysleuglyhis
202530
catgcagtagcaaatggaacattggtaaaaacaatgagtgatgatcaa144
hisalavalalaasnglythrleuvallysthrmetseraspaspgln
354045
attgaggtgacaaatgctacagaattagttcagagcatttcaatgggg192
ilegluvalthrasnalathrgluleuvalglnserilesermetgly
505560
aaaatatgcaacaaatcatatagaattctagatggaagaaattgcaca240
lysilecysasnlyssertyrargileleuaspglyargasncysthr
65707580
ttaatagatgcaatgctaggagacccccactgtgacgcctttcagtat288
leuileaspalametleuglyaspprohiscysaspalapheglntyr
859095
gagagttgggacctctttatagaaagaagcagcgctttcagcaattgc336
glusertrpaspleupheilegluargserseralapheserasncys
100105110
tacccatatgacatccctgactatgcaccgctccgatccattgtagca384
tyrprotyraspileproasptyralaproleuargserilevalala
115120125
tcctcagggacagtggaattcacagcagagggattcacatggacaggt432
serserglythrvalgluphethralagluglyphethrtrpthrgly
130135140
gtaactcaaaacggaagaagtggagcctgcaaaaggggatcagccgat480
valthrglnasnglyargserglyalacyslysargglyseralaasp
145150155160
agtttctttagccgactgaattggctaacaaaatctggaagctcttac528
serphepheserargleuasntrpleuthrlysserglysersertyr
165170175
cccacattgaatgtgacaatgcctaacaataaaaatttcgacaagcta576
prothrleuasnvalthrmetproasnasnlysasnpheasplysleu
180185190
tacatctgggggattcatcacccgagctcaaatcaagagcagacaaaa624
tyriletrpglyilehishisproserserasnglngluglnthrlys
195200205
ttgtacatccaagaatcaggacgagtaacagtctcaacaaaaagaagt672
leutyrileglngluserglyargvalthrvalserthrlysargser
210215220
caacaaacaataatccctaacatcggatctagaccgttggtcagaggt720
glnglnthrileileproasnileglyserargproleuvalarggly
225230235240
caatcaggcaggataagcatatactggaccattgtaaaacctggagat768
glnserglyargileseriletyrtrpthrilevallysproglyasp
245250255
atcctaatgataaacagtaatggcaacttagttgcaccgcggggatat816
ileleumetileasnserasnglyasnleuvalalaproargglytyr
260265270
tttaaattgaacacagggaaaagctctgtaatgagatccgatgtaccc864
phelysleuasnthrglylysserservalmetargseraspvalpro
275280285
atagacatttgtgtgtctgaatgtattacaccaaatggaagcatctcc912
ileaspilecysvalserglucysilethrproasnglyserileser
290295300
aacgacaagccattccaaaatgtgaacaaagttacatatggaaaatgc960
asnasplyspropheglnasnvalasnlysvalthrtyrglylyscys
305310315320
cccaagtatatcaggcaaaacactttaaagctggccactgggatgagg1008
prolystyrileargglnasnthrleulysleualathrglymetarg
325330335
aatgtaccagaaaagcaaaccagaggaatctttggagcaatagcggga1056
asnvalproglulysglnthrargglyilepheglyalailealagly
340345350
ttcatcgaaaacggctgggaaggaatggttgatgggtggtatgggttc1104
pheilegluasnglytrpgluglymetvalaspglytrptyrglyphe
355360365
cgatatcaaaactctgaaggaacagggcaagctgcagatctaaagagc1152
argtyrglnasnsergluglythrglyglnalaalaaspleulysser
370375380
actcaagcagccatcgaccagattaatggaaagttaaacagagtgatt1200
thrglnalaalaileaspglnileasnglylysleuasnargvalile
385390395400
gaaagaaccaatgagaaattccatcaaatagagaaggaattctcagaa1248
gluargthrasnglulysphehisglnileglulysglupheserglu
405410415
gtagaaggaagaattcaggacttggagaaatatgtagaagacaccaaa1296
valgluglyargileglnaspleuglulystyrvalgluaspthrlys
420425430
atagacctatggtcctacaatgcagaattgctggtggctctagaaaat1344
ileaspleutrpsertyrasnalagluleuleuvalalaleugluasn
435440445
caacatacaattgacttaacagatgcagaaatgaataaattatttgag1392
glnhisthrileaspleuthraspalaglumetasnlysleupheglu
450455460
aagactagacgccagttaagagaaaacgcagaagacatgggaggtgga1440
lysthrargargglnleuarggluasnalagluaspmetglyglygly
465470475480
tgtttcaagatttaccacaaatgtgataatgcatgcattgaatcaata1488
cysphelysiletyrhislyscysaspasnalacysilegluserile
485490495
agaactgggacatatgaccattacatatacaaagatgaagcattaaac1536
argthrglythrtyrasphistyriletyrlysaspglualaleuasn
500505510
aatcgatttcagatcaaaggtgtagagttgaaatcaggctacaaagat1584
asnargpheglnilelysglyvalgluleulysserglytyrlysasp
515520525
tggatactgtggatttcattcgccatatcatgcttcttaatttgcgtt1632
trpileleutrpileserphealailesercyspheleuilecysval
530535540
gttctattgggtttcattatgtgggcttgccaaaaaggcaacatcaga1680
valleuleuglypheilemettrpalacysglnlysglyasnilearg
545550555560
tgcaacatttgcatttga1698
cysasnilecysile
565
<210>78
<211>565
<212>prt
<213>流感病毒
<400>78
metlysthrthrileileleuileleuleuthrhistrpalatyrser
151015
glnasnproileserglyasnasnthralathrleucysleuglyhis
202530
hisalavalalaasnglythrleuvallysthrmetseraspaspgln
354045
ilegluvalthrasnalathrgluleuvalglnserilesermetgly
505560
lysilecysasnlyssertyrargileleuaspglyargasncysthr
65707580
leuileaspalametleuglyaspprohiscysaspalapheglntyr
859095
glusertrpaspleupheilegluargserseralapheserasncys
100105110
tyrprotyraspileproasptyralaproleuargserilevalala
115120125
serserglythrvalgluphethralagluglyphethrtrpthrgly
130135140
valthrglnasnglyargserglyalacyslysargglyseralaasp
145150155160
serphepheserargleuasntrpleuthrlysserglysersertyr
165170175
prothrleuasnvalthrmetproasnasnlysasnpheasplysleu
180185190
tyriletrpglyilehishisproserserasnglngluglnthrlys
195200205
leutyrileglngluserglyargvalthrvalserthrlysargser
210215220
glnglnthrileileproasnileglyserargproleuvalarggly
225230235240
glnserglyargileseriletyrtrpthrilevallysproglyasp
245250255
ileleumetileasnserasnglyasnleuvalalaproargglytyr
260265270
phelysleuasnthrglylysserservalmetargseraspvalpro
275280285
ileaspilecysvalserglucysilethrproasnglyserileser
290295300
asnasplyspropheglnasnvalasnlysvalthrtyrglylyscys
305310315320
prolystyrileargglnasnthrleulysleualathrglymetarg
325330335
asnvalproglulysglnthrargglyilepheglyalailealagly
340345350
pheilegluasnglytrpgluglymetvalaspglytrptyrglyphe
355360365
argtyrglnasnsergluglythrglyglnalaalaaspleulysser
370375380
thrglnalaalaileaspglnileasnglylysleuasnargvalile
385390395400
gluargthrasnglulysphehisglnileglulysglupheserglu
405410415
valgluglyargileglnaspleuglulystyrvalgluaspthrlys
420425430
ileaspleutrpsertyrasnalagluleuleuvalalaleugluasn
435440445
glnhisthrileaspleuthraspalaglumetasnlysleupheglu
450455460
lysthrargargglnleuarggluasnalagluaspmetglyglygly
465470475480
cysphelysiletyrhislyscysaspasnalacysilegluserile
485490495
argthrglythrtyrasphistyriletyrlysaspglualaleuasn
500505510
asnargpheglnilelysglyvalgluleulysserglytyrlysasp
515520525
trpileleutrpileserphealailesercyspheleuilecysval
530535540
valleuleuglypheilemettrpalacysglnlysglyasnilearg
545550555560
cysasnilecysile
565
<210>79
<211>20
<212>dna
<213>流感病毒
<400>79
tatgcatcgctccgatccat20
<210>80
<211>21
<212>dna
<213>流感病毒
<400>80
gctccacttcttccgttttga21
<210>81
<211>30
<212>dna
<213>流感病毒
<400>81
aattcacagcagagggattcacatggacag30
<210>82
<211>24
<212>dna
<213>流感病毒
<220>
<221>variation
<222>(7)..(7)
<223>r=aorg
<400>82
catggartggctaaagacaagacc24
<210>83
<211>24
<212>dna
<213>流感病毒
<220>
<221>variation
<222>(18)..(18)
<223>k=gort
<400>83
agggcattttggacaaakcgtcta24
<210>84
<211>18
<212>dna
<213>流感病毒
<400>84
acgctcaccgtgcccagt18
<210>85
<211>28
<212>dna
<213>流感病毒
<400>85
tattcgtctcagggagcaaaagcagggg28
<210>86
<211>42
<212>dna
<213>流感病毒
<400>86
tgtaatacgactcactatagggctccacttcttccgttttga42
<210>87
<211>30
<212>dna
<213>流感病毒
<400>87
gatcgctcttcagggagcaaaagcaggtag30
<210>88
<211>40
<212>dna
<213>流感病毒
<400>88
tgtaatacgactcactatagggcattttggacaaagcgtc40