基于caev的载体系统的制作方法

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专利名称::基于caev的载体系统的制作方法
技术领域
:本发明涉及用于递送多聚核苷酸的慢病毒载体,更具体地涉及用于向非分裂和分裂细胞递送多聚核苷酸的基于羊关节炎-脑炎病毒的载体。
背景技术
:慢病毒是逆转录病毒的一个亚群,能够感染非分裂和分裂细胞。由于来源于慢病毒的载体能够稳定整合到分裂和非分裂细胞的基因组中并且能够介导长期基因表达,所以它是向靶细胞递送外源基因的理想工具(Gilbert和Wong-Staal,2001;Mitrophanousetal.,1999;Naldinietal.,1996;Sauter和Gasmi,2001)。已经从很多脊椎动物物种包括灵长类动物和非灵长类动物中分离出慢病毒,灵长类动物中如人和猴免疫缺陷病毒(HIV-1、HIV-2、SIV),以及非灵长类动物中如猫免疫缺陷病毒(FIV)、牛免疫缺陷病毒(BIV)、马传染性病毒(EIAV)、羊关节炎-脑炎病毒(CAEV)和绵羊髓鞘脱落病毒(visnavirus)。其中,目前了解最多的是HIV和SIV。然而,由于载体有可能重组成有毒力的、致病性的形式,所以这种系统用于人中引起了严重的安全性问题。因此,优选非灵长类慢病毒用于基因治疗。在非灵长类慢病毒载体中,对FIV(Curran和Nolan,2002)和EIAV[US2001/0044149]来源载体的特征描述最多,而其他非灵长类慢病毒载体的进展较少。如所有慢病毒一样,CAEV可以在分裂细胞中以及在终末分化和非分裂细胞中感染和复制。CAEV的多种生物学性质使该病毒成为发展成基因转移/治疗载体的引人注目的候选者。首先,CAEV的正常宿主是山羊,并且没有报道过人感染CAEV的案例。其次,CAEV基因组是慢病毒中距HIV-1系统发生性最远的。再次,和其他慢病毒相比,CAEV的基因组构成相对简单。CAEV基因组含有3个结构基因(gag、pol、env)以及3个调节/辅助基因(vif、tat和rev)。尽管有着这些优势,但开发基于CAEV的递送系统所做的努力并没成功,仅产生了不安全和低效的重组病毒载体生产系统,这使得使用基于CAEV的基因递送系统不实际。1998年,Mselli-Lakhaletal.报道了第一代基于CAEV的载体系统,但该系统的病毒滴度(即10-187TU/ml)在可用水平以下。作者将低效归因于缺乏胞质中基因组RNA积累和载体RNA的包装效率低。该研究的另一个缺点是将感染性野生型病毒(“辅助病毒”)作为其包装系统,这在用于人时很少有实际价值。因此,仍然需要一种安全高效的基于CAEV的慢病毒载体系统,它能够介导广范围的分裂和非分裂细胞中的基因转移。
发明内容本发明一般地涉及生产用于向靶细胞递送外源多聚核苷酸的基于CAEV的慢病毒载体颗粒。这些载体颗粒可用于抗病毒、抗肿瘤和/或基因治疗。在一方面中,本发明提供用于此处所述基于CAEV载体生产系统的转移载体,该转移载体包含(a)CAEV包装序列,该包装序列基本由以下组成(i)CAEV5’LTR和CAEVgag-编码序列之间的非翻译区,以及(ii)连接至所述非翻译区3’端的CAEVgag-编码序列的核苷酸1至X,其中X小于613,(b)多聚腺苷酸化、RNA转运、逆转录和整合所需的、且与所述包装序列形成可操作性连接的顺式作用元件。在本发明的一个实施方案中,X选自60、100、125、150、175、200、225、250、275、300、325、350、375、400、425、450、475、500、525、550、575和600。在本发明的另一个实施方案中,X选自(a)X大于25且小于600,(b)X大于25且小于500,(c)X大于25且小于400,(d)X大于25且小于300,(e)X大于25且小于200,(f)X大于50且小于600,(g)X大于50且小于500,(h)X大于50且小于400,(i)X大于50且小于300,(j)X大于50且小于200,(k)X大于75且小于600,(l)X大于75且小于500,(m)X大于75且小于400,(n)X大于75且小于300,(o)X大于75且小于200,(p)X大于100且小于600,(q)X大于100且小于500,(r)X大于100且小于400,(s)X大于100且小于300,(t)X大于100且小于200,(u)X大于125且小于600,(v)X大于125且小于500,(w)X大于125且小于400,(x)X大于125且小于300,(y)X大于125且小于200,(z)X大于150且小于600,(aa)X大于150且小于500,(bb)X大于150且小于400,(cc)X大于150且小于300,(dd)X大于150且小于200,(ee)X大于200且小于600,(ff)X大于200且小于500,(gg)X大于200且小于400,(hh)X大于200且小于300,(ii)X大于200且小于200,(jj)X大于250且小于600,(kk)X大于250且小于500,(ll)X大于250且小于400,和(mm)X大于250且小于300。在另一个实施方案中,X大于40且小于613。在另一个实施方案中,X大于57且小于613。在另一个实施方案中,X约为327。在本发明的一个实施方案中,gag-编码序列的起始密码子被突变以阻止gag蛋白的翻译。在另一个实施方案中,起始密码子突变成TAG。在本发明的转移载体的另一个实施方案中,gag-编码序列的ATG密码子位于起始密码子ATG下游X碱基对,其中起始密码子被突变以阻止gag蛋白的翻译,并且其中X小于30。在另一个实施方案中X约为21。本发明的转移载体还可以包含RRE区。在本发明的另一个实施方案中,转移载体包含CAEV3’LTR,其中U3区被缺失。本发明的转移载体还可包含异源启动子。在本发明的一个实施方案中,异源启动子是人巨细胞病毒的主要立即早期启动子(HCMVMIEP)。在另一个实施方案中,转移载体是pCAH/SINd1(SEQIDNO68)。本发明的转移载体还可包含含有感兴趣异源多聚核苷酸的转录盒,其可操作性连接至异源启动子(如人巨细胞病毒主要立即早期启动子HCMVMIEP或鼠巨细胞病毒的主要立即早期启动子MCMVMIEP)。这种转移载体允许感兴趣多聚核苷酸掺入到病毒颗粒中,因而提供了扩增含有该多聚核苷酸的被感染宿主细胞数目的方法。本发明还提供基于CAEV慢病毒载体系统,其用于生产可用于向哺乳动物细胞递送外源多聚核苷酸的基于CAEV的、复制缺陷性载体颗粒。载体颗粒能感染和转导哺乳动物细胞。载体系统包含上述转移载体和包装载体系统,其中所述包装载体系统包含包含CAEVgag-pol-编码序列和RRE的第一多聚核苷酸,以及包含病毒包膜编码序列的第二多聚核苷酸。在一个实施方案中,第二多聚核苷酸包含非-CAEVenv-编码序列。在一个实施方案中,第二多聚核苷酸包含VSV-G或GaLV-编码序列。在另一个实施方案中,CAEV载体系统包含含有rev-编码序列的第三多聚核苷酸。在另一个实施方案中,CAEV载体系统包含含有vif-编码序列的第四多聚核苷酸。在另一个实施方案中,上述每种CAEV载体系统的第一多聚核苷酸还包含可操作性连接至CAEVgag-pol-编码序列的异源调节序列。在另一个实施方案中,上述每种CAEV载体系统的第二多聚核苷酸还包含可操作性连接至所述病毒包膜-编码序列的异源调节序列。在另一个实施方案中,第三多聚核苷酸还包含rev-编码序列的异源调节序列。在另一个实施方案中,第三个多聚核苷酸还包含可操作性连接至vif-编码序列的异源调节序列。在本发明的一个实施方案中,CAEV载体系统包含缺失有功能的CAEV包装序列的包装载体系统。在另一个实施方案中,包装载体系统缺失剪接供体位点和gag起始密码子之间的CAEV基因组5’端。在一个实施方案中,CAEV载体系统包含含有第一多聚核苷酸的第一载体和含有第二多聚核苷酸的第二载体。在另一个实施方案中,载体系统包含含有第一多聚核苷酸的第一载体、含有第二多聚核苷酸的第二载体和含有第三多聚核苷酸的第三载体。在另一个实施方案中,载体系统包含含有第一多聚核苷酸的第一载体、含有第二多聚核苷酸的第二载体、含有第三多聚核苷酸的第三载体和含有第四多聚核苷酸的第四载体。第三载体可以是pHYK/rev(SEQIDNO75),第四载体可以是pHYK/vif(SEQIDNO76)。在另一个实施方案中,载体系统包含含有第一多聚核苷酸、第三多聚核苷酸和第四多聚核苷酸的的第一载体以及含有第二多聚核苷酸的第二载体。在一个实施方案中,CAEV载体系统的第一载体包含可操作性连接至异源启动子的CAEVgag-编码序列和RRE。在另一个实施方案中,CAEV载体系统包含第一载体pMGP/RRE(SEQIDNO77)。在一个实施方案中,CAEV载体系统的第二载体是可操作性连接至异源启动子的VSV-G-编码序列。该启动子可以是HCMVMIEP。第二载体还可包含β-珠蛋白内含子。在另一个实施方案中,CAEV载体系统包含第二载体pHGVSV-G(SEQIDNO74)。在一个实施方案中,CAEV载体系统的第二载体是可操作性连接至异源启动子的GaLVenv-编码序列。该启动子可以是MCMVMIEP。第二载体还可包含真核延伸因子-1alpha内含子。在另一个实施方案中,CAEV载体系统包含第二载体pMYKEF-1/env(SEQIDNO72)。本发明的另一方面是生产可用于感染哺乳动物细胞的基于CAEV的慢病毒载体颗粒的方法。该方法包含(a)在适合生产基于CAEV颗粒的条件下,用前述载体系统转染细胞,其中载体颗粒具有感染和转导能力并且是复制缺陷型,以及(b)回收载体颗粒。本发明还提供包含基于CAEV慢病毒载体颗粒和任选地媒介体(carrier)的组合物,其中载体颗粒是通过前述方法制备的。本发明还提供包含前述转移载体或基于CAEV慢病毒载体系统的药盒。本发明还提供包含CAEVgag-pol-编码序列和RRE以及任选地病毒env-编码序列的包装细胞。包装细胞还可包含rev-编码序列和/或vif-编码序列。该细胞可用于将转移载体的RNA形式包装到具有感染和转导能力且是复制缺陷型的载体颗粒中。在一个实施方案中,载体系统包含含有前述第一多聚核苷酸的细胞。载体系统还可含有前述第三和/或第四多聚核苷酸。在另一个实施方案中,载体系统包含含有前述第一多聚核苷酸和第二多聚核苷酸的细胞。载体系统还可含有前述第三和/或第四多聚核苷酸。在另一个实施方案中,载体系统包含含有第一载体的细胞,所述第一载体含有CAEVgag-pol-编码序列和RRE。所述第一载体还可含有rev-编码和/或vif-编码序列。作为替代,所述细胞可包含含有CAEVgag-pol-编码序列和RRE的第一载体、含有rev-编码序列的第二载体和/或含有vif-编码序列的第三载体。在有些实施方案中,载体系统包含一种细胞,所述细胞包含含有CAEVgag-pol-编码序列和RRE的第一载体、和含有病毒env-编码序列的第二载体。第一载体还可含有rev-编码和/或vif-编码序列。作为替代,所述细胞可包含含有CAEVgag-pol-编码序列和RRE的第一个载体、含有病毒env-编码序列的第二载体、和任选地含有rev-编码序列的第三载体和/或含有vif-编码序列的第四载体。本发明的另一方面是向哺乳动物细胞递送多聚核苷酸或多肽或者复制编码所述多肽的多聚核苷酸分子的方法,其包括在可允许所述多聚核苷酸整合到所述细胞基因组中的条件下以及任选地在允许扩增由所述多聚核苷酸编码的所述多肽的条件下使哺乳动物细胞与前述载体颗粒接触。所述哺乳动物细胞可以是分裂细胞、非分裂细胞或CD34+干细胞。该向哺乳动物细胞递送多聚核苷酸或多肽或者复制编码所述多肽的多聚核苷酸的方法,还可包括在载体颗粒接触细胞之前从哺乳动物中分离细胞。该方法还可包括在细胞与载体颗粒接触之后,在培养中扩增所述细胞。该方法还可包括在扩增已接触细胞之前或之后将其重新引入哺乳动物中。本发明还提供向脊椎动物递送多肽的方法,其包括将含有感兴趣异源多聚核苷酸的基于CAEV的慢病毒载体颗粒施用至脊椎动物,其中载体颗粒通过前述方法制备,使得由所递送多聚核苷酸编码的多肽在该脊椎动物中表达,在该脊椎动物中其表达量足以被检测到或引起生物学反应。本发明还提供含有CAEV包装序列的载体,其中CAEV包装序列由以下组成(a)CAEV5’LTR和CAEVgag-编码序列之间的非翻译区,和(b)连接到所述非翻译区3’端的CAEVgag-编码序列的核苷酸1至X,其中X小于613。发明人已经发现,如此处所述,生产所述基于CAEV的慢病毒载体颗粒,相对于现有基于CAEV的载体颗粒增强了慢病毒载体设计中的效率和安全性。通过发现5’LTR距gag起始密码子和gag-编码区之间非翻译区的最适长度而增强了效率,其通过允许高效的包入衣壳而用作高效的包装序列并从而增强病毒滴度。在设计包装质粒中通过使用强异源启动子也提高病毒滴度。通过构建tat-非依赖性转移载体和基于质粒的包装系统而增强了安全性。图1表示CAEV原病毒基因组结构的示意图。图2A表示质粒pMGP/RRE(SEQIDNO77)的示意图。pMGP/RRE(SEQIDNO77)是一个9446bp的质粒,包含位于CAEVgag-pol-编码区(位于bp709-5243)上游的MCMVMIEP区(bp1-660)、RRE区(bp5246-5627或bp5368-5669)以及牛生长激素(BGH)多聚腺苷酸化信号(bp5751-5984)。载体还包含新霉素抗性基因编码区(bp8151-7155)、SV40复制起始位点(bp8509-8152)、ColE1复制起始位点(bp6115-6698)以及氨苄青霉素抗性基因区(bp9362-8528)。图2B表示质粒pMGP/REV/RRE的示意图。pMGP/REV/RRE是一个9924bp的质粒,包含MCMVMIEP区(位于bp1-660)和位于CAEVgag-pol编码区(bp726-5258)上游的CAEV主要剪接供体(bp688-704)、第一外显子rev编码区(bp5383-5494)、RRE区(bp5540-5841)、第二外显子rev编码区(bp5888-6177)以及牛生长激素(BGH)多聚腺苷酸化信号(bp6229-6462)。载体还包含新霉素抗性基因编码区(bp7633-8629)、SV40复制起始位点(bp8987-8630)、ColE1复制起始位点(bp6593-7176)以及氨苄青霉素抗性基因区(bp9840-9006)。图3A表示质粒pCAH/SINd(SEQIDNO73)的示意图。pCAH/SINd(SEQIDNO73)是一个3566bp的质粒,包含HCMVMIEP(bp1-588)、CAEV5’LTR中的R-U5序列区(bp611-772)、RRE区(bp796-1154)以及U3缺失的CAEV3’LTR区(bp1275-1458)。载体还包含ColE1复制起始位点(bp1863-2466)以及卡那霉素抗性基因编码区(bp2698-3510)。图3B表示质粒pCAH/SINd0(SEQIDNO67)的示意图。pCAH/SINd0(SEQIDNO67)是一个3911bp的质粒,包含HCMVMIEP(bp1-588)、CAEV5’LTR的R-U5序列区(bp611-772)、含有引物结合位点(PBS)的剩余非翻译序列(bp773-789)、RRE区(bp1141-1499)以及U3缺失的CAEV3’LTR区(bp1620-1803)。载体还包含ColE1复制起始位点(bp2208-2791)以及卡那霉素抗性基因编码区(bp3043-3855)。图3C表示质粒pCAH/SINd1(SEQIDNO68)的示意图。pCAH/SINd1(SEQIDNO68)是一个4238bp的质粒,包含HCMVMIEP启动子(bp1-588)、CAEV5’LTR的R-U5序列区(bp610-772)、含有PBS位点的剩余非翻译序列(bp773-789)、gag基因的327bp片段(bp1121-1448),其中该片段起始ATG密码子(bp1121-1123)和位于该起始ATG密码子下游的ATG密码子(bp1142-1144)具有ATG点突变成TAG、RRE区(bp1468-1826)以及U3缺失的CAEV3’LTR区(bp1947-2130)。载体还包含ColE1复制起始位点(bp2535-3118)以及卡那霉素抗性基因区(bp3370-4182)。图3D表示质粒pCAH/SINd2(SEQIDNO69)的示意图。pCAH/SINd2(SEQIDNO69)是一个4523bp的质粒,包含HCMVMIEP(bp1-588)、CAEV5’LTR的R-U5序列区(bp610-772)、含有PBS位点的剩余非翻译序列(bp773-789)、gag基因的612bp片段(bp1121-1733),其中该片段起始ATG密码子(bp1121-1123)和位于起始ATG密码子下游的ATG密码子(bp1142-1144)具有点突变、RRE区(bp1753-2111)以及U3缺失的CAEV3’LTR区(bp2232-2415)。载体还包含ColE1复制起始位点(bp2820-3403)以及卡那霉素抗性基因编码区(bp3655-4467)。图3E表示质粒pCAH/SINd3(SEQIDNO70)的示意图。pCAH/SINd3(SEQIDNO70)是一个4819bp的质粒,包含HCMVMIEP(bp1-588)、CAEV5’LTR的R-U5序列区(bp610-772)、含有PBS位点的剩余非翻译序列(bp773-789)、gag基因的908bp片段(bp1121-2029),其中该片段起始ATG密码子(bp1121-1123)和位于起始ATG密码子下游的ATG密码子(bp1142-1144)具有点突变、RRE区(bp2049-2407)以及U3缺失的CAEV3’LTR区(bp2549-2711)。载体还包含ColE1复制起始位点(bp3116-3699)以及卡那霉素抗性基因编码区(bp3951-4763)。图3F表示质粒pCAH/SINd4(SEQIDNO71)的示意图。pCAH/SINd4(SEQIDNO71)是一个5112bp的质粒,包含HCMVMIEP(bp1-588)、CAEV5’LTR的R-U5序列区(bp610-772)、含有PBS位点的剩余非翻译序列(bp773-1120)、gag基因的1198bp片段(bp1121-2319),其中该片段起始ATG密码子(bp1121-1123)和位于起始ATG密码子下游的ATG密码子(bp1142-1144)具有点突变、RRE区(bp2342-2700)以及U3缺失的CAEV3’LTR区(bp2842-3004)。载体还包含ColE1复制起始位点(bp3409-3992)以及卡那霉素抗性基因编码区(bp4244-5056)。图3G表示质粒pCAH/SINd1/hlacZ(SEQIDNO79)的示意图。pCAH/SINd1/hlacZ(SEQIDNO79)是一个pCAH/SINd1(SEQIDNO68)衍生的长8127bp的质粒,它表达lacZ报告基因。该载体包含两个HCMVMIEP启动子区(分别位于bp1-588和bp1866-2460)、CAEV5’LTR的R-U5序列区(bp610-772)、含有PBS位点的剩余非翻译序列(bp773-789)、gag基因的325bp片段(bp1121-1446),其中该片段起始ATG密码子(bp1121-1123)和位于起始ATG密码子下游的ATG密码子(bp1142-1144)具有点突变、RRE区(bp1466-1836)、lacZ基因编码序列(bp2541-5711)以及U3缺失的CAEV3’LTR区(bp5782-6019)。载体还包含ColE1复制起始位点(bp6424-7007)以及卡那霉素抗性基因编码区(bp7259-8071)。图3H表示质粒pCAH/SINd60/hlacZ(SEQIDNO78)的示意图。pCAH/SINd60/hlacZ(SEQIDNO78)是一个长7856bp的质粒,它包含两个启动子区,HCMVMIEP(分别位于bp1-588和bp1595-2189)、CAEV5’LTR的R-U5序列区(bp610-772)、含有PBS位点的剩余非翻译序列(bp773-789bp)、gag基因的60bp片段(bp1121-1181),其中该片段起始ATG密码子(bp1121-1123)和位于起始ATG密码子下游的ATG密码子(bp1142-1144)具有点突变、RRE区(bp1195-1565)、lacZ基因编码序列(bp2270-5440)以及U3缺失的CAEV3’LTR区(bp5511-5748)。载体还包含ColE1复制起始位点(bp6153-6736)以及卡那霉素抗性基因编码区(bp6988-7800)。图4表示质粒pHYK/vif(SEQIDNO76)的示意图。pHYK/vif(SEQIDNO76)是一个长5729bp的质粒,它包含HCMVMIEP(bp1-596)、vif基因编码区(bp691-1380)、BGH多聚腺苷酸化信号(bp1467-1695)、ColE1复制起始位点(bp1826-2409)、新霉素抗性基因编码区(bp3862-2866)以及氨苄青霉素抗性基因编码区(bp5270-4239)。图5表示质粒pHYK/rev(SEQIDNO75)的示意图。pHYK/rev(SEQIDNO75)是一个长5419bp的质粒,它包含HCMVMIEP(bp1-596)、rev基因编码区(bp672-1073)、BGH多聚腺苷酸化信号(bp1157-1385)、ColE1复制起始位点(bp1516-2099)、新霉素抗性基因编码区(bp3552-2556)以及氨苄青霉素抗性基因编码区(bp4960-3929)。图6A表示pHGVSV-G(SEQIDNO74)的示意图。pHGVSV-G(SEQIDNO74)是一个长7623bp的质粒,它包含HCMVMIEP(bp1-596)、β-珠蛋白内含子区(bp714-1599)、VSV-G编码区(bp1632-3312)、BGH多聚腺苷酸化信号(bp3361-3589)、ColE1复制起始位点(bp3720-4303)、新霉素抗性基因编码区(bp5756-4760)、氨苄青霉素抗性基因编码区(bp7164-6133)以及F1复制起始位点(bp7165-7621)。图6B表示质粒pMYKEF1/env(SEQIDNO72)的示意图。pMYKEF1/env(SEQIDNO72)是一个长7579bp的质粒,它包含HCMVMIEP(bp1-665)、人EF1-α内含子区(bp668-1618)、GaLVenv编码区(bp1699-3701)、BGH多聚腺苷酸化信号(bp3885-4118)、ColE1复制起始位点(bp4349-4832)、新霉素抗性基因编码区(bp6290-5284)以及氨苄青霉素抗性基因编码区(bp7496-6666)。图7所示照片表明从转染入人293T靶细胞中的转移载体基因转录的转移载体RNA的相对量。图8所示的两张照片表明通过CAEV(A)和MuLV(B)向人293T靶细胞中的基因转移。图9所示照片表明在已转染293T细胞中所表达的(1、2和3道)以及被包入衣壳并从293T包装细胞释放(4、5和6道)的转移载体RNA的相对量。图10所示照片表明被包入衣壳并从人293T包装细胞释放的转移载体RNA的相对量。图11所示照片表明在由VSV-G或GaLV包膜蛋白所形成假型的慢病毒载体感染和逆转录之后整合的逆转录病毒cDNA的相对量。图12所示照片表明整合到被感染宿主细胞染色体中的病毒载体cDNA的相对量。图13所示两张图片表明(A)对照细胞和(B)G1期-停滞细胞的FACS分析。图14所示两张图片表明HIV-1-、CAEV-和MuLV-衍生的病毒载体对分裂和非分裂细胞的(A)转导细胞的数目以及(B)相对转导效率。具体实施例方式本发明涉及基于CAEV的慢病毒载体系统以及应用所述载体将感兴趣多肽递送入分裂和非分裂细胞的方法。CAEV基因组野生型CAEV病毒具有二聚体RNA基因组(单链、正极性),该RNA基因组通过双链DNA中间体进行复制并被包装在含有核蛋白核心的球形包膜的病毒粒子中。基因组包含编码结构和酶蛋白Gag、Pol和Env的三个基因以及整合病毒基因组两端的长末端重复序列(LTR)。此外,基因组编码三种调节蛋白vif、tat和rev。gag基因编码内在结构蛋白,pol基因编码病毒复制酶,env基因编码介导病毒附着至细胞表面的包膜糖蛋白。Vif蛋白与病毒感染性有关,Tat蛋白与5’LTR的反式激活有关。Rev蛋白及其靶序列RRE(Rev反应元件)与病毒RNA稳定性、病毒RNA剪接的调节以及大RNA(未剪接的和单股剪接的(singlyspliced))从核到质的转运有关。原病毒LTR序列包含U3(位于结构蛋白下游的独特序列元件)、R(基因组两端的短重复序列)、和U5(紧随R序列之后的独特序列元件)区。5’LTR的U3区包含病毒启动子和增强子。基因组的3’端在3’LTR中包含多聚腺苷酸化信号。CAEV的野生型基因组还包含多种顺式激活元件,包括用于原病毒整合在LTR末端的atts(附着位点);在5’LTR控制整合原病毒转录起始的启动子元件;位于5’LTR下游的PBS(引物结合位点);5’-剪接供体位点;包装序列(此处可与包装位点或包装信号互换);邻近3’LTR的ppt(多嘌呤tract)位点以及位于3’LTR的多聚腺苷酸化信号。如此处所用,术语“顺式”(“cis”)用于表示基因存在于同一染色体上或核酸线形部分上。因此,术语“顺式缺陷”表示在核酸线性序列上发现的缺陷。术语“顺式激活”用于表示调节基因对存在于同一染色体上或核酸线性部分上基因的控制作用。例如,影响下游mRNA合成的启动子就是顺式作用控制元件。已知CAEV两种分离株的全基因组序列,且序列以NC_001463(SEQIDNO1)和AF322109(SEQIDNO2)保存在国家生物技术信息中心(theNationalCenterforBiotechnologyInformation,NCBI)数据库中(分别为Saltarellietal.,1990以及Gjerset,B.J.etal.未发表)。本发明的核酸不限于CAEV的具体分离株,而是限于保留基因组序列已知功能的序列。例如,本领域已知病毒复制器件可能发生基因序列的天然变异,产生编码功能相似蛋白的相似核酸序列。NC_001463(SEQIDNO1)和AF322109(SEQIDNO2)基因组序列的序列比对见表1。如表1可见,序列间存在相当的核酸一致性,但核酸水平的差异也是明显的。尤为重要的是表2所注释的CAEVgag区的变异性(SEQIDNO3-6)。在表3-6(SEQIDNO7-14)中可分别发现NC_0014635’LTR、pol、rev和vif基因与AF322109相应基因的序列比对。还已知并且保存了CAEV基因组的很多部分序列。如,登记号AY081139、AY101347、AY101348、AY047362、AF402668、AF402667、AF402666、AF402665、AF402664、AJ305042、AJ305041和AJ305040都提供了CAEV巴西分离株中gag基因的序列。登记号AF015181、L78453、L78451、L78450、L78447和L78446也包含多种CAEV分离株中gag基因的序列。登记号X64828和M63106包含多种CAEV分离株中rev基因的序列。登记号AF015182、AJ305053、K03327、L78448、L78452和U35814包含多种CAEV分离株中pol基因的序列。表7可见NC_001463gag基因(SEQIDNOs15、17)和AF015181的gag基因(SEQIDNO16、18)之间的序列比对。表8可见NC_001463gag基因(SEQIDNOs19、25)与来自AF402664(SEQIDNOs20、26)、AF402665(SEQIDNOs21、27)、AF402666(SEQIDNOs22、28)、AF402667(SEQIDNOs23、29)、AF402668(SEQIDNOs24、30)的gag基因之间的序列比对。表9可见NC_001463gag基因(SEQIDNOs31、35)与来自AJ305040(SEQIDNOs32、36)、AJ305041(SEQIDNOs33、37)、AJ305042(SEQIDNOs34、38)的gag基因之间的序列比对。表10可见NC_001463gag基因(SEQIDNOs39、41)与来自AY047362(SEQIDNOs40、42)的gag基因之间的序列比对。表11可见NC_001463gag基因(SEQIDNOs43、45)与来自AY081139(SEQIDNOs44、46)的gag基因之间的序列比对。表12可见NC_001463gag基因(SEQIDNOs47、50)与来自AY101347(SEQIDNOs48、51)和AY101348(SEQIDNOs49、52)的gag基因之间的序列比对。表13可见NC_001463gag基因(SEQIDNOs53、59)与来自L78446(SEQIDNOs54、60)、L78447(SEQIDNOs55、61)、L78450(SEQIDNOs56、62)、L78451(SEQIDNOs57、63)和L78453(SEQIDNOs58、64)的gag基因之间的序列比对。通过VectorNTI(Informax,USA)应用如下参数进行比对两两比对间隙开放罚分15间隙延伸罚分6.6多重序列比对间隙开放罚分15间隙延伸罚分6.6间隙分离罚分范围8表14总结了上面所列gag基因序列的序列比对的百分一致性值。表15总结了NC_001463(SEQIDNO1)和AF322109(SEQIDNO2)之间全基因组比对、和gag、5’LTR、pol、rev和vif区比对的百分一致性。考虑到已知两个CAEV分离株的基因组序列,还有来自多种CAEV分离株的大量部分序列,并且可以容易地分辨出共有序列,使用多种CAEV序列来实施本发明将不需要过度的实验。本发明的CAEV载体本发明的载体提供一种在广泛的系统发生范围中不依赖于宿主细胞核来复制和表达多聚核苷酸或基因的方法。这种载体介导的将异源核酸掺入宿主细胞中被称为宿主细胞的转染或感染,其中感染是指应用病毒颗粒,而转染是指应用裸露的核酸分子。术语“基因”表示包含产生多肽或前体所必需的控制和编码序列的DNA序列。术语“多聚核苷酸”或“核酸分子”,如此处可互换,表示任意长度的核苷酸多聚体,比如两个或更多个,并且包括DNA和RNA。核苷酸可以是脱氧核糖核苷酸、核糖核苷酸、核苷酸类似物(包括修饰的磷酸结构、碱基或糖)或任意通过合适酶如DNA聚合酶或RNA聚合酶可以被结合到多聚体中的底物。多肽可以由全长编码序列所编码或由编码序列的任意部分所编码,只要能够保留多肽的期望活性即可。术语“野生型”表示具有从天然来源中分离出的该基因或基因产物的特征的基因或基因产物。野生型基因是指种群中最经常出现的基因并因此被直接称为该基因的“正常”或“野生型”形式。相反,术语“修饰”或“突变”表示当与野生型基因或基因产物相比时在序列和或功能特征上表现出变化的基因和或基因产物(即改变的特征)。可以分离天然存在的突变体,并根据当与野生型基因或基因产物相比时它们具有特征改变的事实来鉴定。必须注意,如本说明书和所附权利要求书中所使用的,除非文中另有指明,否则单数形式“一个”、“一种”(a、an、the)等包括对应的复数形式。因此,如“一个多聚核苷酸”包括多个多聚核苷酸以及“一个干细胞”包括多个细胞。如此处所用的,术语“逆转录病毒”表示复制周期中利用逆转录酶的RNA病毒。逆转录病毒基因组RNA被逆转录酶转化成双链DNA。病毒的这种双链DNA形式能够整合到感染细胞的染色体中;一旦整合,便称作“原病毒”。原病毒用作RNA聚合酶II的模板并指导编码生产新病毒颗粒所需的结构蛋白和酶的RNA分子的表达。如此处所用,术语“慢病毒”涉及能引起缓慢发展性疾病的一组(或属)逆转录病毒。该组所包括的病毒包括人免疫缺陷病毒(HIV);导致绵羊脑炎(visna)或肺炎(maedi)的髓鞘脱落-呼吸急促病毒(visna-maedi)、羊关节炎-脑炎病毒(CAEV);马传染性贫血病毒(EIAV);猫免疫缺陷病毒(FIV);牛免疫缺陷病毒(BIV)以及猴免疫缺陷病毒(SIV)。这些病毒引起的疾病特征在于潜伏期长和病程拖延。通常病毒潜伏性地感染单核细胞和巨嗜细胞,并通过它们传播到其他细胞。如此处所用,术语“载体(vector)”表示将多聚核苷酸(如DNA)片段从一个细胞转移到另一个细胞的核酸分子。术语“载体(vehicle)”有时可与“载体(vector)”相互替换。任何形式的载体(vehicle)或载体(vector)都包括在此定义范围内。例如,载体(vector)包括但不限于病毒颗粒、质粒、转座子等。用于构建本发明的载体的标准技术是本领域技术人员公知的,并且在Sambrooketal.,MolecularCloningALaboratoryManual2ndEd.(ColdSpringHarbor,N.Y.,1989)这类参考中可以发现。多种策略都可以用于连接DNA片段,策略的选择有赖于DNA片段末端的性质并且技术人员很容易做出选择。本发明适合的多聚腺苷酸化序列包括但不限于牛生长激素(BGH)多聚腺苷酸化信号(Pfarretal.,1986)、SV40早期区多聚腺苷酸化位点(Halletal.,1983)和SV40晚期区多聚腺苷酸化位点(CarswellandAlwine,1989)、β-珠蛋白polyA以及单纯疱疹病毒胸苷激酶polyA。本发明的启动子可包含来源于哺乳动物或病毒的启动子,并且足以在细胞中指导位于远处序列(即连接至启动子序列5’端的序列)的转录。启动子区还可以包括增强或抑制转录的控制元件。合适的启动子包括但不限于人或鼠巨细胞病毒立即早期启动子(HCMVMIEP或MCMVMIEP)、延伸因子1alpha(ef-1α)以及劳斯肉瘤病毒长末端重复启动子(pRSV)。内含子序列也可与启动子组合。内含子序列包括但不限于ef-1α内含子和β-珠蛋白内含子。还可以使用诱导表达系统。诱导系统的实例包括但不限于蜕皮激素-诱导的哺乳动物表达系统(Invitrogen,CA,USA)以及Tet-On和Tet-Off基因表达系统(Clontech,CA,USA)。细胞或组织特异性启动子可用于在特定细胞群体中定向表达基因序列。为了辅助表达,本发明的载体任选地可以包括位于启动子或终止子序列上游以及编码区下游的增强子序列。本发明的载体还可包含附加的核酸序列,如内含子序列、定位序列或信号序列,足以使细胞高效而有效地加工由载体核酸所表达的蛋白质。内含子序列的实例包括β-珠蛋白内含子(Kimetal.,2002)和人EF-1α内含子(Kimetal.,2002)。将该类附加序列插入载体中,如果期望转录,使之与启动子序列可操作性连接,或者如果期望翻译或加工,使之另外与起始和加工序列可操作性连接。作为替代,插入序列可置于载体中任何位置。术语“可操作性连接”用来描述基因序列和启动子或其他调节或加工序列之间的连接,使得由可操作性连接的启动子序列指导基因序列的转录,由可操作性连接的翻译调节序列指导基因序列的翻译,由可操作性连接的加工序列指导基因序列的翻译后加工。术语“SIN载体”表示自失活的载体,该载体在3’LTR中具有截短的U3区。在逆转录过程中,截短的U3区在5’LTR复制,导致失去转录能力和对内源启动子的干扰作用。转移载体的包装序列基本由以下组成(i)CAEV5’LTR和CAEVgag-编码序列间的非翻译区,以及(ii)连接至所述非翻译区3’端的CAEVgag-编码序列的核苷酸1至X,其中X小于613。在本发明的一个实施方案中,X选自60、100、125、150、175、200、225、250、275、300、325、350、375、400、425、450、475、500、525、550、575和600。在本发明的另一个实施方案中,X选自(a)X大于25且小于600,(b)X大于25且小于500,(c)X大于25且小于400,(d)X大于25且小于300,(e)X大于25且小于200,(f)X大于50且小于600,(g)X大于50且小于500,(h)X大于50且小于400,(i)X大于50且小于300,(j)X大于50且小于200,(k)X大于75且小于600,(l)X大于75且小于500,(m)X大于75且小于400,(n)X大于75且小于300,(o)X大于75且小于200,(p)X大于100且小于600,(q)X大于100且小于500,(r)X大于100且小于400,(s)X大于100且小于300,(t)X大于100且小于200,(u)X大于125且小于600,(v)X大于125且小于500,(w)X大于125且小于400,(x)X大于125且小于300,(y)X大于125且小于200,(z)X大于150且小于600,(aa)X大于150且小于500,(bb)X大于150且小于400,(cc)X大于150且小于300,(dd)X大于150且小于200,(ee)X大于200且小于600,(ff)X大于200且小于500,(gg)X大于200且小于400,(hh)X大于200且小于300,(ii)X大于200且小于200,(jj)X大于250且小于600,(kk)X大于250且小于500,(ll)X大于250且小于400,和(mm)X大于250且小于300。在另一个实施方案中,X大于40且小于613。在另一个实施方案中,X约为327。在转移载体的一个实施方案中,起始gag翻译的密码子被突变(如ATG变为TAG、TTG、CTG或ATT)或缺失。术语“密码子”表示DNA或信使RNA分子的三核苷酸序列,它代表指导特定氨基酸结合到生长的多肽链中。转移载体还包含异源启动子以及一或多个顺式激活序列。如此处所用,术语“包装信号”或“包装序列”表示病毒RNA包装到病毒衣壳或颗粒中所需的位于CAEV基因组5’LTR附近的序列。多种逆转录病毒载体利用包装病毒基因组所需的最小包装信号(也被称为psi[ψ]序列)。因此,如此处所用,术语“包装序列”、“包装信号”、“psi”以及符号“ψ”用于表示形成病毒颗粒期间包装CAEVRNA链所需的非编码序列。在本发明的另一个实施方案中,转移载体还包含转录盒。此处所用术语“转录盒”表示含有一组特定遗传元件的核酸片段或节段,通常是指可操作性连接至异源启动子的表达感兴趣多肽的多聚核苷酸。可将转录盒作为单个单元从载体或质粒中去除以及插入载体或质粒中。本发明转移载体的说明性实例如图3C所示。图3C表示质粒pCAH/SINd1(SEQIDNO68)。pCAH/SINd1(SEQIDNO68)是一个长4238bp的质粒,包含HCMVMIEP启动子、CAEV5’LTR的R-U5序列区、含有PBS的剩余非翻译序列、具有ATG到TAG双点突变的gag基因的327bp片段、RRE区以及U3缺失的CAEV3’LTR区。该载体还包含ColE1复制起始位点(bp2535-3118)以及卡那霉素抗性基因区(bp3370-4182)。转移载体的其他说明性实例见图3A-3H。本发明提供包含上述转移载体和包装载体系统的CAEV载体系统。包装载体系统包含第一和第二多聚核苷酸载体序列。第一多聚核苷酸载体序列包含CAEVgag-pol和RRE-编码序列,第二多聚核苷酸包含病毒包膜编码序列。在一个实施方案中,第二多聚核苷酸编码非-CAEV包膜。如此处所述,短语“结构基因”表示编码将病毒基因组包入衣壳(如包装)所需蛋白质的多聚核苷酸序列,包括gag、pol和env。本发明第一包装载体的说明性实例如图2A所示。图2A表示质粒pMGP/RRE(SEQIDNO77)。该质粒包含9446个碱基对,并且包括MCMVMIEP区、CAEVgag-pol-编码区、RRE区以及牛生长激素(BGH)多聚腺苷酸化信号。该载体还包含新霉素抗性基因编码区、SV40复制起始位点、ColE1复制起始位点以及氨苄青霉素抗性基因区。通过利用来自另一个亲缘相近病毒的包膜,有可能改变本发明病毒载体可以感染的宿主细胞范围。换言之,通过利用某些病毒的包膜蛋白参与其他病毒衣壳包装的能力,有可能扩大本发明CAEV载体的宿主范围。逆转录病毒-来源env基因的实例包括但不限于水泡性口炎病毒(VSV-G)、长臂猿白血病病毒(GaLV)、劳斯肉瘤病毒(RSV)、莫洛尼小鼠白血病病毒(MoMuLV)、小鼠乳腺肿瘤病毒(MMTV)和人免疫缺陷病毒(HIV)的G-蛋白。所有这些病毒包膜蛋白都能高效地与其他病毒基因组和基质成分形成假型病毒粒子。如此处所述,术语“假型”表示包含一种病毒的核酸却具有另一病毒的包膜蛋白的病毒颗粒。通常,VSV-G或GaLV假型载体的宿主范围非常广泛,通过超离心可以沉淀至高浓度的滴度(Burnsetal.,1993),并仍然保持高水平的感染性。本发明第二包装载体的其他说明性实例如图6A和6B所示。图6A表示pHGVSV-G(SEQIDNO74)。pHGVSV-G(SEQIDNO74)是一个长7623bp的质粒,它包含HCMVMIEP、β-珠蛋白内含子区、VSV-G编码区、BGH多聚腺苷酸化信号、ColE1复制起始位点、新霉素抗性基因编码区、氨苄青霉素抗性基因编码区以及F1复制起始位点。图6B表示质粒pMYKEF1/env(SEQIDNO72)。该质粒有7579bp,它包括HCMVMIEP、人EF1-α内含子区、GaLVenv编码区、BGH多聚腺苷酸化信号、ColE1复制起始位点、新霉素抗性基因编码区以及氨苄青霉素抗性基因编码区。在本发明的另一个实施方案中,包装载体包含编码Rev的第三多聚核苷酸。在感染细胞中,Rev结合到病毒转录本中的Rev-应答元件(RRE),引起复制晚期阶段中病毒结构蛋白的特征性单股剪接和未剪接转录本的转录。因此,Rev介导病毒基因表达的时间调节。因为哺乳动物细胞剪接机制与mRNA从核中合成部位到胞质的转运相偶联,所以Rev还影响含RRE的病毒转录本的转运。本发明第三包装载体的说明性实例如图5所示。图5表示质粒pHYK/rev(SEQIDNO75)。pHYK/rev(SEQIDNO75)是一个长5419bp的质粒,它包含HCMVMIEP、rev基因编码区、BGH多聚腺苷酸化信号、ColE1复制起始位点、新霉素抗性基因编码区以及氨苄青霉素抗性基因编码区。在本发明的另一个实施方案中,包装载体包含编码Vif的第四多聚核苷酸。并入Vif对于病毒粒子的感染和包装来说可以是必需的,这有赖于所选的包装细胞系。本发明第四包装载体的实例如图4所示。pHYK/vif(SEQIDNO76)是一个长5729bp的质粒,它包含HCMVMIEP、vif基因编码区、BGH多聚腺苷酸化信号、ColE1复制起始位点、新霉素抗性基因编码区以及氨苄青霉素抗性基因编码区。当逆转录病毒DNA转染到细胞中之后,它可以整合或可以不整合到染色体DNA中并转录,从而产生包含ψ序列的全长逆转录病毒RNA。在这些条件下,仅有载体RNA包装到病毒衣壳结构中。这些完整但复制缺陷的病毒颗粒随后能够用于向靶细胞相对高效地递送逆转录病毒载体。如此处所用,术语“复制缺陷”表示不能完整有效复制因而不能产生感染性病毒粒子的病毒(如复制缺陷型慢病毒后代)。术语“复制型(replication-competent)”表示野生型病毒或能够复制的突变病毒,使得病毒的病毒复制能够产生感染性病毒粒子(如复制型慢病毒后代)。也可以考虑诱导型以及非诱导型包装。在诱导型包装细胞和包装细胞系中,响应至少一种诱导物而生产CAEV颗粒。在诱导型细胞系的优选实施方案中,诱导物是Tat。在非诱导型包装细胞系和包装细胞中,生产慢病毒颗粒不需要诱导物。CAEV载体序列本发明的功能等同序列还包括保留与各自天然序列基本相同功能的多种CAEV基因组片段。这些片段包含特定感兴趣遗传元件的至少约10个、15个连续核苷酸、至少约20个连续核苷酸、至少约24、50、60、80、100、120、140、160、180、200、220、240、260、280、300、340、360、380或多至全部连续核苷酸。通过用限制性酶切割天然病毒基因组;通过合成来自病毒基因组天然核苷酸序列的核苷酸序列;或者通过PCR技术可以获得这些片段。具体参见(Mullis和Faloona,1987)和(Erlich,1989)。另外,各种载体成分的变体,如那些定点突变所产生的,也包括在本发明的方法中。如下更详细描述,用于确定功能等同的方法在本领域中可以获得。“变体”旨在包括基本相似的序列。因此,对于核苷酸序列或氨基酸序列,变体包括与病毒载体系统的各种成分功能等同的序列。变体核苷酸序列还包括已经生成、例如经定点突变生成、但仍然保持天然序列功能的合成来源的核苷酸序列。通常,本发明的核苷酸序列变体或氨基酸序列变体与各自天然核苷酸序列具有至少70%、通常80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%或99%的序列一致性。本发明变体包括的多聚核苷酸(如载体)包含由与此处公开的载体序列(SEQIDNOs67-79)具有至少70%、80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%或99%一致性的序列、基本由这样的序列组成、或由这样的序列组成。技术人员了解所公开核酸构建体的很多保守性变异产生功能一致的构建体。特定核酸序列的保守性变异表示编码一致或基本一致性氨基酸序列的核酸,或者在核酸不编码氨基酸序列时表示基本一致性序列。由于遗传密码的简并性,大量功能一致的核酸编码任意给定的多肽。例如,由于遗传密码的简并性,“沉默替换”(即不引起所编码多肽改变的核酸序列的替换)是编码氨基酸的每一核酸序列的内在性质。相似地,包装或可包装构建体的氨基酸序列中一或多个氨基酸的“保守性氨基酸替换”被替换为具有高度相似的不同氨基酸,因为与已公开构建体的高度相似性这也容易被鉴定。例如,密码子CGU、CGC、CGA、CGG、AGA和AGG均编码氨基酸精氨酸。因此,在由密码子指定为精氨酸的每个位置,该密码子可变成任一个所述对应密码子而不改变编码多肽。这种核酸变异是“沉默变异”,是“保守性修饰变异”的一种。此处每一编码多肽的核酸序列还描述每种可能的沉默变异。技术人员将会知道可以通过标准技术修饰核酸中每个密码子(除了AUG,其通常是甲硫氨酸唯一的密码子)以产生功能一致的分子。因此,编码多肽的核酸的每个“沉默变异”隐含在任何描述序列中。而且,技术人员将会知道,改变、添加或缺失编码序列中单个氨基酸或少部分氨基酸(典型地小于5%,更为典型地小于1%)的单个取代、缺失或添加,是“保守性修饰变异”,其中所述变异导致氨基酸被替换为化学相似的氨基酸。提供功能相似性氨基酸的保守性替换表在本领域是公知的。如下六组每组中包含彼此可相互替换的氨基酸1)丙氨酸(A)、丝氨酸(S)、苏氨酸(T);2)天冬氨酸(D)、谷氨酸(E);3)天冬酰胺(N)、谷氨酰胺(Q);4)精氨酸(R)、赖氨酸(K);5)异亮氨酸(I)、亮氨酸(L)、甲硫氨酸(M)、缬氨酸(V);和6)苯丙氨酸(F)、酪氨酸(Y)、色氨酸(W)。也可参见Creighton(1984)ProteinsW.H.FreemanandCompany。最后,添加不改变核酸分子活性的序列,如非功能性序列,是对基本核酸的保守性修饰。每种公开序列的这种保守性替换的变异是本发明的一个特征。对于本发明载体系统所用的各种全长或成熟多肽的氨基酸序列,变体包括通过以下方法从天然多肽衍生的那些多肽缺失(所谓截短)或添加一或多个氨基酸至天然多肽的N-端和/或C-端;在天然多肽的一或多个位点处缺失或添加一或多个氨基酸;或在天然多肽的一或多个位点处替换一或多个氨基酸。这些变体可以来自例如遗传多态性或人为操作。这些操作方法在本领域是公知的。技术人员将会知道很多途径均可在给定核酸构建体中产生变化。这些公知方法包括定点突变、用简并寡聚核苷酸进行的PCR扩增、将含有所述核酸的细胞暴露于突变剂或辐射、化学合成期望的寡聚核苷酸(如与连接和/或克隆相结合来产生大的核酸)以及其他已知技术。参见(Gillam和Smith,1979)、(Roberts、Cheetham和Rees,1987)和Sambrook、Innis、Ausbel、Berger、NeedhamVanDevanter和Mullis(如上述)。天然核酸序列或天然多肽的变体与天然序列或天然多肽基本一致。变体可存在少至1至10个氨基酸残基的差异,如6-10、少至5个、少至4、3、2或甚至1个氨基酸残基。核苷酸序列的变体可存在少至1至30个核苷酸的差异、如6-20、5、4、3、2甚至1个核苷酸残基的差异。当变体核苷酸序列或氨基酸序列的指定连续节段与参考序列的核苷酸序列或氨基酸序列比对并比较时,“序列一致性”旨在表示在变体序列和参考序列之内发现的相同核苷酸或氨基酸残基。序列比对和确定序列间一致性的方法在本领域中是公知的。对于两核苷酸序列间的最佳比对,相对于参考核苷酸序列,变体核苷酸序列的连续节段可以有添加核苷酸或缺失核苷酸。类似情况,为了两氨基酸序列的最佳比对,相对于参考氨基酸序列,变体氨基酸序列的连续节段可以有添加氨基酸残基或缺失氨基酸残基。用于比较参考核苷酸序列或者参考氨基酸序列的连续节段包含至少20个连续核苷酸或氨基酸残基,并可以是30、40、50、100或更多核苷酸或氨基酸残基。通过分配间隙罚分,可以进行校正以增加序列一致性,这与在变体核苷酸序列或氨基酸序列中包括间隙相关。可以用数学算法来确定两序列间的一致性百分比。例如可以用Smith-Waterman同源搜索算法用仿射6间隙搜索(anaffine6gapsearch)来确定氨基酸序列的一致性百分比,其中间隙开放罚分为12和间隙延伸罚分为2,BLOSUM矩阵为62。作为替代,使用Smith-Waterman同源搜索算法来确定核苷酸序列的一致性百分比,其中间隙开放罚分为25和间隙延伸罚分为5。序列一致性的这种确定可以通过例如用TimeLogicVersionG的DeCypher硬件加速器来进行。Smith-Waterman同源搜索算法在Smith和Waterman中教导,其通过参考并入本文。作为替代,可以使用利用默认参数的GCGGap比对程序(WisconsinGeneticComputingGroup,SuiteVersion10.1)。GCGGap程序应用Needleman和Wunch算法,对于核苷酸序列比对可以使用间隙开放罚分3和间隙延伸罚分1。用于比较两序列的数学算法的另一个优选的、非限制性实例是Karlin和Altschul算法(Karlin和Altschul,1990),并在Karlin和Altschul(Karlin和Altschul,1993)中改进。这种算法已并入到Altschuletal.的NBLAST和XBLAST程序中(Altschuletal.,1990)。可以在NBLAST程序中设置评分=100、字长=12进行BLAST核苷酸搜索,以获得具有足够序列一致性的核苷酸序列。可以在XBLAST程序中设置评分=50、字长=3进行BLAST蛋白质搜索,以获得具有足够序列一致性的氨基酸序列。为获得间隙比对用于比较目的,可以利用Altschuletal.所述的GappedBLAST(Altschuletal.,1997)。作为替代,可以用PSI-Blast进行叠代搜索来检测分子间的远相关性。参见上述Altschuletal.,(1997)。当使用BLAST、GappedBLAST和PSI-Blast程序时,可以使用各自程序的默认参数(如XBLAST和NBLAST)。参见http://www.ncbi.nlm.nih.gov。用于比较序列的数学算法的另一个非限制性实例是Myers和Miller算法(1988)CABIOS411-17。该算法并入到ALIGN程序中(2.0版),它是GCG序列比对软件包的一部分。当利用ALIGN程序比较氨基酸序列时,可以用PAM120权重余量表(weightresiduetable)、间隙长度罚分为12以及间隙罚分为4。VectorNTI(Informax,USA)也可用来确定氨基酸序列的一致性百分比。技术人员可基于提供的序列以及本领域通常有关CAEV的知识来选择本发明的期望核酸。慢病毒的生活周期、基因组结构、发育调节以及相关分子生物学已经成为十年来广泛研究的焦点。很多慢病毒基因组中很多突变的特异性作用是已知的。此外,一些CAEV株的核酸序列变异是已知的。而且,根据关于蛋白质和核酸性质的一般知识,技术人员能够选择具有与本文序列表所公开的核酸和多肽的活性相似或等同的合适序列。最后,核酸的大部分修饰可通过常规筛选技术在适于期望性质的分析中来评价。例如,编码多肽免疫学性质的改变可通过合适的免疫学分析来检测。其他性质的变化如核酸与互补核酸杂交、编码蛋白质的氧化还原或热稳定性、疏水性、对蛋白质裂解的敏感性、或聚集倾向均可根据标准技术进行分析。感兴趣多聚核苷酸如本领域技术人员所了解的,插入的感兴趣多聚核苷酸的核苷酸序列可以是任意核苷酸序列。例如,多聚核苷酸序列可以是报告基因序列或选择标记基因序列。如此处所用,报告基因序列是任意基因序列,当其表达时导致产生其存在或活性可被监测的蛋白质。合适的报告基因的实例包括半乳糖激酶、β-半乳糖苷酶、氯霉素乙酰转移酶、β-内酰胺酶、绿色荧光蛋白、增强型绿色荧光蛋白等的基因。作为替代,报告基因序列可以是其表达能够产生影响细胞生理的基因产物的任意基因序列。本发明的多聚核苷酸序列可包含一或多个已经具有一或多个启动子、起始序列或加工序列的基因序列。选择标记基因序列指能够表达一种蛋白质的基因序列,所述蛋白质的存在允许选择性地扩增含有它的细胞。选择标记基因的实例包括能赋予宿主抗生素抗性(如嘌呤霉素、潮霉素、新霉素、Zeocin等)、或赋予宿主氨基酸类似物抗性、或允许细菌在其他碳源上或在非允许培养条件下生长的基因序列。报告或选择标记基因序列足以允许在正常细胞中识别或选择载体。在本发明的一个实施方案中,报告基因序列可编码哺乳动物细胞中一般不存在的酶或其他蛋白质,从而这些酶或蛋白质的存在可以明确地确定载体在这些细胞中的存在。本发明的转移载体还允许将异源核酸或多聚核苷酸掺入病毒颗粒中,从而提供了扩增含有异源核酸的感染宿主细胞数目的方法。异源多聚核苷酸的掺入促进病毒颗粒内异源核酸的复制以及随后其中异源蛋白质的生产。异源蛋白质在此定义为一种蛋白质或其片段,其中宿主细胞不表达该蛋白质的全部或部分。如果核酸或基因序列不是天然存在于用来向细胞递送基因的病毒载体野生型中,那么其被称为异源。此处所用的术语异源核酸序列或多聚核苷酸序列旨在表示核酸分子(优选DNA)。多聚核苷酸序列或异源多聚核苷酸序列还可包含期望产物的编码序列,其中期望产物如合适生物学活性蛋白质或多肽、免疫原性或抗原性蛋白质或多肽、或治疗活性蛋白质或多肽。多肽可以补充宿主细胞中内源蛋白质表达的不足或不存在。该类基因序列可有多种来源,包括DNA、cDNA、合成DNA、RNA或其组合。这种基因序列可以包含基因组cDNA,所述基因组cDNA可包括或不包括天然存在的内含子。而且,这种基因组DNA可以与启动子序列或多聚腺苷酸化序列一同获得。本发明的基因序列优选是cDNA。可通过多种方法获得基因组DNA或cDNA。基因组DNA可以通过本领域公知方法从合适细胞中提取和纯化。作为替代,mRNA可从细胞中分离获得并通过逆转录或其他方法用来制备cDNA。作为替代,多聚核苷酸序列可包含与RNA序列互补的序列,如反义RNA序列,该反义序列可以施用至个体来抑制该个体的细胞中互补多聚核苷酸的表达。异源基因的表达可提供免疫原性或抗原性蛋白质或多肽来获得抗体反应。因此而产生的抗体可从动物体液中收集获得,如血液、血清或腹水。异源基因还可以是任意可转录的感兴趣核酸。通常外源基因编码多肽。优选地多肽具有一些治疗益处。多肽可以补充宿主细胞中内源性蛋白质表达的不足或不存在。多肽可赋予宿主细胞新的特性,如嵌合信号受体。参见U.S.Pat.No.5,359,046。普通技术人员能够确定此处所教导或本领域公知的外源基因操作技术的适当性。例如,技术人员将知道外源基因的大小是否适合包入衣壳以及外源基因产物是否能够适当表达。本发明中可用的具体异源蛋白质对其并不关键。可用于本发明的这些异源蛋白质的具体实例包括肌营养不良蛋白(dystrophin)(Hoffman,Brow和Kunkel,1987)、凝血因子VIII(Wionetal.,1985)、囊性纤维化跨膜转导调节蛋白(CysticFibrosisTransmembraneRegulatorProtein,CFTR)(Andersonetal.,1991;Crawford,1991)、鸟氨酸氨基甲酰转移酶(OTC)(Murakamietal.,1988)和α1-抗胰蛋白酶(Fagerhol和Cox,1981)。编码很多异源蛋白质的基因在本领域中是公知的,并且可以从基因组或cDNA文库中克隆[前述Sambrooketal]。这种基因的实例包括肌营养不良蛋白基因(Leeetal.,1991)、凝血因子VIII基因(Tooleetal.,1984)、CFTR基因(Rommensetal.,1989;Riordan,1989)、OTC基因(Horwichetal.,1984)以及α1-抗胰蛋白酶基因(Lemarchandetal.,1992)。此外,编码异源蛋白质的基因,如用于治疗血管增生疾病如动脉硬化的Rb(Changetal.,1995)以及用于治疗癌症(Willsetal.,1994;Clayman,1995)和HIV病(Bridges和Sarvet,1995)的p53均可用于本发明。不总是需要载体去编码功能性、异源基因产物,即它还可以编码部分基因产物来作为真核酶的抑制剂(Warne,Viciana和Downward,1993;Wang,1991)。还可期望通过本发明方法引入分子来调节(modulate)细胞中基因调节分子的表达。术语“调节”指当基因过度表达时抑制其表达,或当低表达时提高其表达。当细胞增殖性疾病与基因表达有关时,可使用在翻译水平干扰基因表达的核酸序列。该策略可利用例如反义核酸、核酶或三联体试剂(triplexagents),通过反义核酸或三联体试剂掩蔽其mRNA或通过用核酶切割来阻断特定mRNA的转录或翻译。反义核酸是和特异性mRNA分子的至少一部分互补的DNA或RNA分子。在细胞中,反义核酸与相应的mRNA杂交形成双链分子。因为细胞不翻译形成双链的mRNA,所以反义核酸干扰mRNA的翻译。优选约15个或更多核苷酸的反义寡聚物,因为它便于合成,并且当引入靶细胞后与更大的分子相比其引起问题的可能性小。使用反义方法抑制基因的体外翻译在本领域中是公知的(Marcus-Sekura,1988)。反义核酸可用于阻断突变蛋白或显性活性基因产物的表达,如在阿尔茨海默病中积累的淀粉样前体蛋白。这种方法也可用于治疗亨廷顿舞蹈病、遗传性帕金森病以及其他疾病。反义核酸也可用于抑制毒性相关蛋白质的表达。使用寡核苷酸阻止转录可以是通过已知作为三联体策略的机制,因为寡聚物缠绕双螺旋DNA,形成三链螺旋。因此,可以设计三联体化合物来识别所选基因上的独特位点(Maher,Wold和Dervan,1991;Helene,1991)。核酶是指具有特异性切割其他单链RNA能力的RNA分子,其切割方式类似于DNA限制性内切酶。通过改变编码这些RNA的核苷酸序列,可以设计识别并切割RNA分子中特异性核苷酸序列的工程分子(Cech,1988)。该策略的主要优点是仅仅使具有特定序列的mRNA失活。可以期望转移编码生物学效用调节剂的核酸。归属该类的是免疫增强剂(immunopotentiatingagents),包括编码分类为“白细胞介素”如白介素1至12的多种细胞因子的核酸。尽管干扰素工作机制不一定相同但也归属该类,尤其是γ-干扰素(γ-IFN)、肿瘤坏死因子(TNF)和粒细胞-巨嗜细胞集落刺激因子(GM-CSF)。可以期望向骨髓细胞或巨嗜细胞递送这种核酸来治疗先天性酶缺乏或免疫缺陷。编码生长因子、毒性肽、配体、受体或其他生理重要蛋白质的核酸也可以引入特定非分裂细胞。因此,本发明的重组CAEV载体系统可用于通过抗-HIV分子处理HIV-感染的细胞(如T-细胞或巨嗜细胞)。此外,例如呼吸上皮可用具有囊性纤维化跨膜转导调节蛋白(CFTR)基因的本发明重组慢病毒感染,来治疗囊性纤维化。因此,本发明的重组CAEV载体系统可用于治疗多种人类疾病。CAEV载体系统在人类疾病中的可能应用的具体实例包括但不限于阿尔茨海默病、帕金森病、肌萎缩性侧索硬化病、亨廷顿舞蹈病、β-地中海贫血、视网膜色素变性、粘多糖疾病、脑白质萎缩病、X-连锁SCID(X-linkedSCID)、苯丙酮尿症、酪氨酸血症(tryosinemia)、血友病A和B、Wilson氏病、LDL受体缺乏、人免疫缺陷和杜氏肌营养不良(Duchenne’sdystrophy)。CAEV载体颗粒在本发明的一种方法中,可根据此处公开的方法并结合本领域技术人员公知的技术制备感染性和复制缺陷的CAEV载体颗粒。所述方法包括用本发明载体表达系统转染慢病毒允许细胞;在转染细胞中生产CAEV衍生颗粒;和从细胞中收集病毒颗粒。如此处所用术语“转染”表示将外来DNA引入到真核细胞中。可以通过本领域多种已知方式进行转染,包括但不限于磷酸钙-DNA共沉淀、DEAE-葡聚糖-介导的转染、polybrene-介导的转染、电穿孔、显微注射、脂质体融合、脂质转染(lipofection)以及原生质体融合。这些技术是本领域公知的。如此处所用,术语“转导”表示利用病毒或逆转录病毒颗粒通过感染而非转导的方式递送基因。在一些实施方案中,转导逆转录病毒载体。因此,“转导基因”是通过慢病毒或载体感染或原病毒整合而已经被导入细胞的基因。在某些实施方案中,CAEV病毒载体颗粒将基因转导至“靶细胞”或宿主细胞中。促进在细胞中生产感染性病毒颗粒的步骤还可用常规技术进行,如标准细胞培养生长技术。收集感染性病毒颗粒的步骤还可用常规技术进行。例如,如本领域已知,可以通过收集细胞培养的上清来收集感染性颗粒。任选地,如果期望可以纯化收集的病毒颗粒。适合的纯化技术对本领域技术人员而言是公知的。如果技术人员需要,可以用本发明的载体和方法制备CAEV储液。制备病毒储液的方法是本领域公知的,例如见(Soneokaetal.,1995)和(LandauandLittman,1992)。在生产本发明储液的一种方法中,用本发明的载体系统转染慢病毒允许细胞。细胞然后在合适的细胞培养条件下生长,并如上述从细胞培养物中收集CAEV颗粒。适合的允许细胞系包括但不限于人细胞系293、293T和HeLa、猴细胞系Vero以及山羊细胞系GSM和Ch1Es。本发明的载体还可用于制备稳定的包装细胞(即稳定表达CAEV结构蛋白的细胞,细胞自身不能产生感染性病毒颗粒)和病毒生产细胞(VPC)。制备表达逆转录病毒蛋白的包装细胞的方法是本领域公知的,并且例如在Teminetal.的U.S.Pat.No.4,650,764提出的方法作为实例,其中所公开的全部内容并入此处。在本发明的范围内,包装细胞包括含有来自至少一个本发明所述CAEV包装载体的CAEV核酸序列的慢病毒允许宿主细胞,其核酸序列是包装信号缺陷的,因此使细胞自身可生产至少一种CAEV结构蛋白,但不能生产有复制能力的感染性病毒。根据已知方法,用前面提供的合适CAEV核酸序列转染CAEV允许宿主细胞(如人胚肾293或293T细胞)来制备包装细胞。所得包装细胞因此能够表达并生产至少一种CAEV结构蛋白。但是,包装细胞仍然不能生产重组CAEV病毒。然后可用其他核酸序列即转移载体来转染包装细胞,所述转移载体含有感兴趣异源基因和适当的包装信号。一旦被附加序列转染,包装细胞即可用来提供含有异源基因的CAEV病毒储备,但病毒自身是没有复制能力的。所得的病毒生产细胞(VPC)从而能够生产含有感兴趣异源基因的感染性病毒颗粒。基因转移和基因治疗单基因变化导致的很多人类遗传疾病是基因治疗的主要候选对象。如此处所用,术语“基因治疗”或“基因转移”定义为出于医药治疗目的而将基因插入细胞中。已知有很多基因治疗的应用,尤其是通过干细胞的遗传插入,因此它们是公知的并已被广泛评述。术语“靶”用于表示CAEV载体旨在转导所述细胞。用于治疗性基因转移的靶细胞,离体或者体内,包括但不限于造血干细胞、淋巴细胞、血管内皮细胞、呼吸道上皮细胞、角化细胞、骨胳和肌肉细胞、肝细胞、神经细胞以及癌细胞。本发明的基因转移技术还可用于阐明肽的加工以及鉴定多种蛋白质的功能结构域。为了研究在加工和细胞命运方面的细胞特异性差异,可将蛋白质的克隆cDNA或基因组序列导入不同的离体或体内靶细胞。通过使编码序列置于强启动子控制下,可以获得相当量的期望蛋白。此外,参与蛋白质加工、细胞内分选或生物活性的特定残基可通过编码序列中离散残基的突变引起的变化来确定。本发明的基因转移技术还可用于提供控制蛋白质表达和评价其调节细胞事件的能力的工具。有些蛋白质功能,比如它们在分化中的作用,可以在组织培养中进行研究,然而其他一些则需要在发育的不同时间重新引入到体内系统,以监测相关性质的变化,基因转移提供研究核酸序列和调节特定基因表达的细胞因子的方法。这种研究的一种策略是将待研究的调节元件融合到报告基因上,随后分析报告基因的表达。基因转移在理解和为疾病状态提供治疗中还具有相当有潜力的用途。有很多遗传疾病其缺陷基因是已知的并且已经被克隆。有些情况下,这些克隆基因的功能是已知的。通常将上述疾病状态分为两类缺乏状态,通常是酶,一般以隐性形式遗传,以及不平衡状态,至少有时涉及调节或结构蛋白,其以显性形式遗传。对于缺乏状态疾病,基因转移可用于将正常基因引入受影响的组织中用于替代治疗,以及用反义突变建立该疾病的动物模型。对于不平衡疾病状态,基因转移可用于在模型系统中建立疾病状态,然后再用于努力克服该疾病状态。因此本发明的方法允许治疗遗传疾病。如此处所用,通过部分或完全矫正引起疾病或使之更严重的缺乏或不平衡来治疗疾病状态。也可以利用核酸序列的位点特异性整合来引起突变或校正缺陷。本发明的方法也可用于神经元、神经胶质、成纤维细胞或间质细胞移植或“移植”,其包括移植离体感染本发明重组慢病毒的细胞、或者体内感染入中枢神经系统中或腔室中或硬膜下宿主脑表面上。这些移植方法对本领域技术人员而言是已知的,并描述于NeuralGraftingintheMammalianCNS,Bjorklund和Stenevi,eds.(1985)。对于缺乏蛋白质产物的疾病,基因转移可将正常基因引入受影响组织用于替代治疗,以及用反义突变建立该疾病的动物模型。例如,可以期望在CAEV颗粒中插入编码因子VIII或IX的核酸,来感染肌肉、脾或肝细胞。已知有很多基因治疗的应用,尤其是经干细胞的遗传插入,因此它们是公知的并已被大量评述。如此处所用,术语“干细胞”包括但不限于造血干细胞、神经干细胞、间质细胞(尤其是肌肉)干细胞和肝脏干细胞。干细胞能够在体内再生组织。造血干细胞是来源于人造血祖细胞的前体细胞。利用造血干细胞的基因治疗还可用于治疗淋巴样和髓样细胞的遗传异常,这些异常通常导致产生缺陷型蛋白质或基因表达水平异常。对于很多疾病,引入缺陷型基因的正常拷贝或功能同源物并产生即使小量的缺失基因产物也会有有益作用。同时,预期基因产物的过量表达不会有有害作用。如下提供非穷举的疾病列表,基因转移入造血干细胞对这些疾病有潜在用途。这些疾病通常包括骨髓疾病、红系细胞缺陷、代谢疾病等。造血干细胞基因治疗有利于治疗血细胞的遗传疾病,如α-和β-地中海贫血、镰刀形细胞贫血以及血友病A和B,其中珠蛋白基因或凝血因子基因(如因子IX和因子X基因)有缺陷。另一个良好实例是对严重性联合免疫缺陷疾病(SCIDS)的治疗,此类患者缺少腺苷脱氨酶(ADA),ADA帮助清除对T和B淋巴细胞有毒性的某些副产物,这些副产物使患者不能抵抗感染。这类患者是接受基因治疗的理想候选对象,向其造血干细胞而不是象以往那样向患者的淋巴细胞引入ADA基因。其他疾病包括慢性肉芽肿,其中噬中性粒细胞表达缺陷型细胞色素b,以及巨嗜细胞中异常的葡糖脑苷酶(glucocerebrosidase)基因产物引起的Gaucher病。此外,神经退行性疾病如帕金森病是基因治疗的一个引人注目的靶,其中通过向纹状体和黑质引入GDNF(胶质细胞源性神经营养因子)基因(Kordoweretal.,2000)。治疗多种形式癌症的策略也包括在基因治疗中。CAEV载体可以携带编码比如毒素或凋亡诱导剂的基因,它们能有效地特异性杀死癌细胞。通过在只有肿瘤细胞表达自杀基因的条件下向癌化造血细胞引入自杀基因也可以实现特异性杀死肿瘤细胞。自杀基因产物通过将正常无毒药物转变成有毒衍生物从而赋予细胞致死敏感性。例如,胞嘧啶脱氨酶将无毒性物质5’-氟胞嘧啶转变成有毒衍生物5-氟尿嘧啶(Mullen,Kilstrup和Blaese,1992)。肿瘤特异性淋巴细胞可以被遗传修饰,例如向肿瘤部位递送具有抗肿瘤活性的基因产物,从而克服与系统性递送这些基因产物相关的毒性。基因治疗策略还可用于向骨髓细胞提供对化疗毒性作用的抗性。基因治疗还可用于防止或对抗病毒感染,如HIV和HTLV-1感染。例如,造血干细胞可以被遗传修饰从而使细胞抵抗HIV感染。一条途径是通过用反义RNA或者通过破坏现有病毒调节通路来特异性抑制病毒基因表达。与逆转录病毒RNA互补的反义RNA已经表现出可以抑制多种逆转录病毒的复制(To,Booth和Neiman,1986),包括HIV(RhodesandJames,1991)和HTLV-1(vonRuden和Gilboa,1989)。造血干细胞基因治疗可以应用的另一方面在于缓解自身免疫疾病。治疗性基因可以编码例如B或T细胞信号分子,它们能重新构建正常凋亡信号,导致自身反应性细胞死亡或被清除。用于诊断、研究或基因治疗的离体细胞转化(如通过将转化细胞重新输注到宿主机体中)是本领域技术人员公知的。在本发明的一个实施方案中,从对象机体中分离细胞,用含有感兴趣多肽的本发明载体转染细胞,并将细胞重新输注到对象(如患者)机体中。适合离体转化的各种细胞型是本领域技术人员公知的。特别优选的细胞是上述干细胞(参见,例如Freshney(1994)CultureofAnimalCells,aManualofBasicTechnique,thirdeditionWiley-Liss,NewYork,此处所引用的参考讨论如何从患者中分离和培养细胞)。通过本领域公知方法培养转化细胞。也参见Kuchler(1977)BiochemicalMethodsinCellCultureandVirology,Kuchler,R.J.,Dowden,HutchinsonandRoss,Inc.,以及Atlas(1993)CRCHandbookofMicrobiologicalMedia(Parksed)CRCpress,BocaRaton,Fl。哺乳动物细胞系经常是单层培养的细胞形式,但是也可使用哺乳动物细胞悬浮培养。作为替代,细胞可来自细胞库中保存的细胞(如血库)。哺乳动物细胞系的说明性实例包括HEC-1-B细胞系、VERO和Hela细胞、中国仓鼠卵巢(CHO)细胞系、W138、BHK、Cos-7或MDCK细胞系(例如参见Freshney上述)。T细胞或B细胞也可用于有些离体基因转移操作中。多种用于分离T和B细胞的技术是公知的。表面标志分子的表达有助于这些细胞的鉴定和纯化。总之,本发明的病毒载体可用于稳定转导分裂或非分裂细胞,和稳定表达异源基因。利用该载体系统现在有可能向分裂或非分裂细胞中引入编码能影响细胞生理的蛋白质的基因。本发明的载体因此可用于疾病状态或细胞生理实验性改变的基因治疗。药盒(kit)本发明的另一个目的是提供包含用于此处所述方法的载体的药盒或药物递送系统。所有施用靶向逆转录病毒颗粒所需的基本材料和试剂可以组装到药盒中(如包装细胞构建体或细胞系)。药盒的成分可以多种配方形式提供。所述一或多种CAEV颗粒可与一或多种药剂(如化疗剂)一起配制成单个制药接受的组合物或分开的制药接受的组合物。这些药盒或药物递送系统的成分也可以干燥或冻干的形式提供。当试剂或成分以干燥形式提供时,通常通过添加合适的溶剂使其重构,所述溶剂也可以提供在另一种容器装置中。本发明的药盒还可含有关于靶向CAEV颗粒的剂量和或给药信息的说明书。典型地,本发明的药盒或药物递送系统也包括盛装封闭结构小瓶(vial)用于商业销售的装置,例如,盛装期望小瓶的注塑或吹塑容器。无论容器的数量或类型,药盒还可包括,或一同装入,辅助注射/施用或放置最终复杂复合物到对象体内的设备。这种设备可以是涂药器、吸入器、注射器、吸管、镊子、量勺、滴眼器或任意这类医学认可的递送载体。以下实施例举例说明本发明的多个方面,但从未意图限制其范围。实施例以下实施例用来举例说明本发明的某些实施方案和方面,不应解释为对其范围的限制。以下实施例证明这一发现,即本发明基于重组CAEV的慢病毒载体系统与公知的基于HIV-1的慢病毒系统在表达方面一样有效。这些实施例表明,本发明基于CAEV的载体颗粒生产系统的基因组RNA转录、包装、转导、逆转录以及整合的水平与基于HIV-1的慢病毒载体系统相当,而基于HIV-1的慢病毒载体系统早已作为高效的基因转移系统而被接受(Naldinietal.,1996)。这是首次对构建高滴度的基于CAEV载体系统的报导,该系统基于最低程度的三质粒共转染方法,仅需要表达gag-pol和env基因以及任选地rev基因。材料和方法质粒构建亲本质粒。本发明的CAEV载体衍生自亲本质粒pWTE-BM和质粒pCAEV-LTR,是由MarieSuzan博士(InstitutNationaldelaSanteetdelaRechercheMedicale“INSERM”,France)友情提供的。pWTE-BM质粒含有除了0.4kbHindIII片段以外的全长基因组CAEVcDNA,所述HindIII片段包含部分env、rev和U3区以及1337碱基对的填充片段。质粒pCAEV-LTR包含质粒pWTE-BM中缺失的0.4kbHindIII片段(Saltarellietal.,1990;Saltarelli,1993)。两种载体均不能产生野生型病毒。CAEVgag-pol表达载体(pMGP/RRE)(SEQIDNO77)和pMGP/REV/RRE)。pMGP/RRE(SEQIDNO77)质粒是PWTE-BM衍生的gag-pol表达质粒(如图2A所示)。pMGP/RRE(SEQIDNO77)质粒包含强的异源MCMV主要立即早期基因启动子(MCMVMIEP)、gag-pol基因以及rev应答元件(RRE)。pMGP/RRE(SEQIDNO77)质粒还编码作为抗生素选择标记的新霉素抗性基因。为了构建质粒,通过使用对几个PCR和亚克隆步骤的标准操作方案将pWTE-BM的gag-pol基因片段(CAEV基因组的512至5046核苷酸)亚克隆至pGL2-Basic克隆载体(Promega,WI,USA)。从质粒pMYK中切下MCMVMIEP片段(Kimetal.,2002),然后插入到gag基因上游,将RRE区(CAEV基因组的核苷酸7824至核苷酸8183或核苷酸7849至核苷酸8150)插入到pol基因下游。pMGP/REV/RRE是另一个gag-pol表达质粒(如2B图所示),其包含CAEVrev基因。此外,CAEV的主要剪接供体位点(CAEV基因组的核苷酸330至核苷酸346)插入到MCMV启动子下游。转移载体(pCAH/SINd系列)。构建pCAH/SINd系列的质粒(如图3A-3H所示)(SEQIDNO67-71、73、78和79),来鉴定设计本发明转移载体的最佳包装序列。该系列中的每个质粒被设计成包含不同长度的5’非翻译区和gag-编码区的起始,以便一段一段比较该区中各种长度的作用。出于某些安全性考虑,这些质粒被设计成具有缺失3’LTR的U3区的SIN(自我失活)载体。为了在缺少反式激活因子tat条件下高水平表达来自转移载体的载体RNA,5’LTR的U3区替换成HCMVMIEP。此外,转移载体包括多聚腺苷酸化、RNA转运、逆转录以及整合所需的所有已知顺式激活序列元件。pCAH/SINd系列中的质粒(SEQIDNO67-71、73、78和79)按照如下构建。将pCAH/SINd(缺乏PBS的阴性对照载体)(SEQIDNO73)(图3A)设计成在5’LTR仅含有5’非翻译序列(R和U5区)(CAEV基因组核苷酸1至核苷酸163)。将pCAH/SINd0(SEQIDNO67)(图3B)设计成含有全部5’非翻译区(CAEV基因组核苷酸1至核苷酸511)。将pCAH/SINd1(SEQIDNO68)(图3C)设计成含有全部5’非翻译区和没有点突变的gag基因的327bp片段(CAEV基因组核苷酸1至核苷酸839)。将pCAH/SINd2(SEQIDNO69)(图3D)设计成含有全部5’非翻译区和有点突变的gag基因的612bp片段(CAEV基因组核苷酸1至核苷酸1124)。将质粒pCAH/SINd3(SEQIDNO70)(图3E)设计成含有全部5’非翻译序列和有点突变的gag基因的908bp片段(CAEV基因组核苷酸1至核苷酸1420)。将质粒pCAH/SINd4(SEQIDNO71)(图3F)设计成含有全部5’非翻译序列和有点突变的gag基因的1198bp片段(CAEV基因组核苷酸1至核苷酸1710)。通过将由HCMVMIEP和lacZ基因组成的表达盒插入到pCAH/SINd1(SEQIDNO68)中来构建pCAH/SINd1/hlacZ(SEQIDNO78)(图3G)。除了gag基因长度以外,质粒pCAH/SINd60/hlacZ(SEQIDNO78)(图3H)与pCAH/SINd1(SEQIDNO68)具有相同的设计,它包含有点突变的gag基因的前60bp片段(CAEV基因组核苷酸1至核苷酸569)。CAEVvif表达载体(pHYK/vif)(SEQIDNO76)。已知快速和高效的病毒复制需要vif基因,将vif基因(CAEV基因组核苷酸5006至核苷酸5695)克隆到真核表达载体pHYK(Kimetal.,2002)(图4)中。CAEVrev表达载体(pHYK/rev)(SEQIDNO75)。rev基因通过与RRE相互作用在转录后水平调节病毒基因表达,其由两个外显子组成(第一外显子位于CAEV基因组的核苷酸6012至6123,第二外显子在核苷酸8514至8803)。Rev/RRE系统促进将未剪接RNA运出细胞核,并被认为是慢病毒复制必需的。通过RT-PCR合成rev基因的全长cDNA并亚克隆到pHYK载体中(图5)。病毒包膜基因表达载体。此处所用的包膜基因表达载体系统是质粒pHGVSV-G(SEQIDNO74)和质粒pMYKEF1/env(SEQIDNO72)(图6A和6B)。将质粒pHGVSV-G(SEQIDNO74)设计成表达水泡性口炎病毒G(VSV-G)糖蛋白并且包含具有β-珠蛋白内含子的HCMVMIEP作为启动子。将质粒pMYKEF-1/env(SEQIDNO72)设计成表达长臂猿白血病病毒(GaLV)包膜蛋白并且包含具有真核延伸因子-1α内含子的MCMVMIEP作为启动子。基于MuLV-和HIV-1的质粒。作为对照载体系统,本发明使用pMFG/lac/Zpuro和pHP/lacZ载体,它们分别是来源于鼠白血病病毒(MuLV)(Kimetal.,1997)和1型人免疫缺陷病毒(HIV-1)(Naldinietal.,1996)的含lacZ的逆转录病毒载体。对于MuLV和HIV-1载体系统的包装质粒,分别使用pEQPAM3(Personsetal.,1998)和pCMVΔR8-2。除了编码功能性HIV-1vpu基因和env基因中缺失1.3-kbBglII片段以外,HIV-1包装质粒pCMVΔR8-2与pCMVΔR9(Naldinietal.,1996)相同。载体颗粒的生产通过脂质体介导瞬时转染三种或更多种质粒进入293T细胞来生产假型化的基于CAEV的慢病毒载体颗粒,其中293T细胞在转染之前一天以5×105细胞每6孔培养皿铺板。gag-pol表达质粒、转移载体质粒和env-编码质粒按照1∶1∶1摩尔比实施三质粒共转染。gag-pol表达质粒、转移载体质粒、env-编码质粒和rev-表达质粒按照3∶3∶3∶1摩尔比实施四质粒共转染。gag-pol表达质粒、转移载体质粒、和env-编码质粒、rev-表达质粒和vif-表达质粒按照3∶3∶3∶1∶1摩尔比实施五质粒共转染。48小时之后收集含有病毒载体颗粒的培养上清,用0.45μM滤膜(Nalgene,NY,USA)澄清,立即使用或者贮存于-70℃超低温冰箱。体外转导转导如下进行在8μg/mlpolybrene存在条件下,向293T细胞中添加病毒载体颗粒持续4小时,随后添加新鲜培养基。48小时后,细胞在由1%甲醛和0.2%戊二醛组成的溶液中进行固定,并于37℃在含200μg5-溴-4-氯-3-吲哚-β-D-半乳糖苷(X-Gal,Promega,WI,USA)、4mM亚铁氰化钾、4mM铁氰化钾和2mMMgCl2的溶液中染色12小时,之后进行Beta-Gal表达分析。通过计数蓝斑数目作为每mlLacZ形成单位(LFU/ml)来确定滴度。RT-PCR分析通过利用TRIzolLS试剂(GIBCOBRL,CA,USA)的方法从培养细胞或培养上清中提取总RNA。用无RNase的DNaseI(1单位/μgDNA,20分钟,37℃)(Promega,WI,USA)处理总RNA以清除DNA污染。加入与DNaseI一起提供的RQ1DNase终止溶液来停止DNaseI反应,通过使用RNeasymini试剂盒(Qiagen,Germany)的方法回收RNA。通过逆转录(RT)反应将纯化的RNA逆转录成cDNA(90分钟,37℃)。具体而言,在MuLV逆转录酶、寡聚dT引物或C-端特异性引物和dNTP混合物存在下实施RT反应。实施PCR扩增用特异性引物来半定量分析模板DNA。具体而言,在热稳定ExTaq聚合酶、序列特异性DNA引物和dNTP混合物存在下从cDNA或染色体DNA合成PCR产物DNA。Southern杂交分析用DNeasyTissue试剂盒(Qiagen,Germany)从转导有假型HIV-1或CAEV载体颗粒的细胞、以及假转导的对照细胞中制备基因组DNA。用BamHI和KpnI消化来自HIV-1载体转导细胞的10μg基因组DNA。用EcoRI和SspI双消化来自CAEV载体转导的细胞和阴性对照细胞的各10μg基因组DNA。用0.7%琼脂糖凝胶电泳分离消化的基因组DNA,并转移到带正电荷的尼龙膜上(Roche,Germany)。用lacZ基因特异性引物(正向引物CTGGCGTAATAGCGAAGAGG(SEQIDNO65)、反向引物AACTCGCCGCACATCTGAAC(SEQIDNO66))通过PCR制备dig(地高辛)标记的探针,根据Dig应用手册进行southern杂交(Roche,Germany)。细胞的生长抑制和生长抑制细胞的FACS分析用蚜肠霉素(Sigma,USA)(25μg/ml)处理来生长抑制293T细胞,之后用CAEV病毒载体颗粒转导。作为阳性或阴性对照,用HIV-1载体或MuLV逆转录病毒载体平行转导细胞。转导后两天,用针对beta-gal活性的X-gal对细胞进行染色。在蚜肠霉素处理的培养物中,转染之前和之后都存在蚜肠霉素。经FACS分析确认细胞的生长抑制。在PBS中洗涤蚜肠霉素处理或未处理的对照细胞,在70%乙醇中在-20℃下固定过夜,之后用碘化丙锭(100μg/ml)(Sigma,USA)和RNAseA(100μg/ml)(Qiagen,Germany)在室温下处理1小时。通过FACS分析评价细胞,计算细胞周期G1、S和G2/M期中总活细胞的百分比(BectonDickinson,Sanjose,CA)。实施例1生产基于CAEV的慢病毒载体颗粒用CAEVgag-pol表达质粒、CAEVenv-表达质粒和转移载体质粒的最低程度的三质粒系统瞬时共转染人293T细胞来生成复制缺陷型慢病毒载体颗粒的复制。在四质粒系统中,再加上CAEVrev表达质粒;在五质粒系统中,再加上CAEVvif表达质粒。为了高效包装,转移载体设计成包含gag-编码序列的起始,其中在起始ATG密码子和位于下游的ATG密码子位置引入突变(ATG变成TAG)以防止gag蛋白的表达。将RRE包括其中来促进包装效率,在四-和五-质粒系统中从载体表达rev以支持CAEVmRNA的转出。在转移载体质粒中插入内部HCMV-MIEP启动子驱动的β-半乳糖苷酶基因作为报告基因。用强病毒启动子HCMVMIEP替换5’LTR的U3区,从而允许载体基因组不依赖于tat。转移载体RNA转录水平。转移载体基因组RNA的转录水平是介导从包装细胞中生产高滴度重组病毒载体的关键因素之一。本发明中,为了安全高效地转录转移载体RNA,用HCMV增强子/启动子元件来构建HCMV/CAEV杂合LTR启动子系统。为了检验含有杂合LTR启动子的pCAH/SINd(SEQIDNO67-71、73、78和79)系列中转移载体质粒的转录水平,通过脂质体介导的转染,将每个转移载体质粒与包装质粒(pMGP/RRE(SEQIDNO77)、pHYK/rev(SEQIDNO75)、pHYK/vif(SEQIDNO76)、pHGVSV-G(SEQIDNO74)或pMYKEF1/env(SEQIDNO72)一起引入人T细胞。孵育48小时之后,从已转染细胞中纯化总RNA,并实施逆转录酶-聚合酶链式反应(RT-PCR)分析来测定载体RNA转录。将CAEV转移载体的PCR引物组(RRE引物组)设计为用于合成编码部分RRE区的348-bpPCR产物。将另一组HIV-1转移载体pHRlacZ(Naldinietal。1996)的PCR引物组(lacZ引物组)设计为用于合成编码部分lacZ基因的645bpPCR产物。如图7所示,本发明的CAEV转移载体产生与基于HIV-1慢病毒转移载体相当水平的RNA转录本。载体颗粒的形成和释放。为了检查成熟且有感染性病毒载体颗粒的形成和释放,在向人293T细胞中脂质体介导共转染pMGP/RRE(SEQIDNO77)gag-pol表达质粒、pHGVSV-G(SEQIDNO74)env表达质粒、pHYK/rev(SEQIDNO75)rev表达质粒、pHYK/vif(SEQIDNO76)vif表达质粒和pCAH/SINd60/hlacZ(SEQIDNO78)转移载体质粒之后生产CAEV载体颗粒(DuBridgeetal.,1987)。转染48小时之后,收集转染细胞的培养上清,在8μg/mlpolybrene存在下施加到新鲜的人293T细胞中用于感染。结果证明本发明的五质粒系统能够产生与基于MuLV的慢病毒载体系统(pEQPAM3、pMFG/lacZ/puro、pHGVSV-G(SEQIDNO74))相当的病毒载体颗粒滴度(Ory,Neugeboren和Mulligan,1996;Personsetal.,1998)(图8所示)。实施例2Rev和Vif表达对载体颗粒生产的作用为了确定CAEVrev和vif调节基因表达对载体颗粒生产的作用,平行测试载体颗粒生产系统(1)缺失rev-和vif-编码序列的三质粒系统(pCAH/SIN、pMGP/RRE(SEQIDNO77)、pHGVSV-G(SEQIDNO74)或pMYKEF1/env(SEQIDNO72)),(2)缺失vif-编码序列的四质粒系统(pCAH/SIN、pMGP/RRE(SEQIDNO77)、pHGVSV-G(SEQIDNO74)或pMYKEF1/env(SEQIDNO72)、pHYK/rev(SEQIDNO75))以及(3)同时含有rev-和vif-编码序列的五质粒系统(pCAH/SIN、pMGP/RRE(SEQIDNO77)、pHGVSV-G(SEQIDNO74)或pMYKEF1/env(SEQIDNO72)、pHYK/rev(SEQIDNO75)、pHYK/vif(SEQIDNO76))在载体颗粒生产方面的效率。向293T细胞转染各个系统的质粒。转染后第二天,分别从转染细胞和转染细胞培养基中提取转移载体的RNA和病毒粒子RNA,并用作RT-PCR模板与lacZ引物组一起来检测转移载体RNA基因组。如图9所示,虽然包装细胞中转移载体RNA的表达水平不依赖于rev和vif基因的表达(图9的1、2和3道),在rev缺失时包入衣壳的转移载体RNA的量(图9,4道)远远低于rev存在时的量(图9,5道)。但令人惊奇的是,用vif存在时包入衣壳的RNA通过RT-PCR测定的载体颗粒滴度(图9,6道)低于用CAEVvif缺失时包入衣壳的RNA通过RT-PCR测定的载体颗粒滴度(图9,5道)。这些数据表明CAEVrev和vif不是载体颗粒生产所需的,但rev优选用于高效载体颗粒生产。值得注意的是,本发明关于vif表达的结果与Harmacheetal.报导的不一致(Harmacheetal.,1995;Harmacheetal.,1996),其中报导vif基因是CAEV在山羊滑膜细胞中高效复制所必需的,并且将影响病毒复制周期的晚期步骤(如,RNA包入衣壳、病毒颗粒从宿主细胞中释放)。对这种不一致的一种可行解释可以是在生产重组CAEV载体颗粒中用的是人293T细胞而不是山羊细胞。这一解释支持Seroudeetal.提出的假设,即vif和病毒生产细胞间的物种特异性限制可调节vif对病毒感染性的功能(Seroudeetal.,2002)。实施例3最优包装信号序列的鉴定为鉴定CAEV转移载体RNA包入衣壳的最优包装信号序列,按照如下比较一系列含有CAEVgag-编码区不同部分以及位于5’LTR和gag起始密码子之间非翻译区的质粒的载体颗粒生产效率。用pMGP/RRE(SEQIDNO77)gag-pol表达质粒、pHGVSV-G(SEQIDNO74)env表达质粒、pHYK/rev(SEQIDNO75)rev表达质粒、pHYK/vif(SEQIDNO76)vif表达质粒以及pCAH/SINd(SEQIDNO67-71、73、78和79)转移载体系列质粒共转染人293T细胞。作为阴性对照,在缺少包装质粒条件下转染CAEV转移载体pCAM/lacZ(L)。转染后第二天,从转染细胞培养基中提取病毒粒子RNA,并用作RT-PCR模板与RRE引物组一起来检测CAEV转移载体系列RNA基因组,或与lacZ引物组一起来检测HIV-1转移载体RNA基因组。如图10所示,从用pCAH/SINd1(SEQIDNO68)转染的生产病毒的293T细胞收获的培养基中,获得强PCR产物信号,这表明高效释放含有病毒RNA的病毒颗粒,其中pCAH/SINd1包含完整的5’LTR以及gag区的前327bp(图10,3道)。该信号与从阳性对照、HIV-1载体中获得的信号相当,这表明包入衣壳内的本发明CAEV转移载体RNA的量与基于HIV-1转移载体的该量相当(图10,8道)。具有gag-编码区前612bp或更长的CAEV转移载体包装效率显著降低(4、5和6道)。当所用转移载体缺失gag-编码序列时检测不到PCR产物信号(图10,1和2道)。阴性对照仅转染有转移载体,而阳性对照HIV-1载体转染有pCMVΔR8-2、pHR’/lacZ和pHGVSV-G(SEQIDNO74)(图10,7和8道)。总之,仅当转移载体包括少于约600bp的N-端gag-编码序列以及位于5’LTR和gag起始密码子之间的整个非翻译区时,在包装细胞中转移载体RNA才高效地包入衣壳。这些结果证明包装信号内RNA的二级结构的作用比RNA包入衣壳中的一级结构更为重要。实施例4CAEV载体病毒粒子的假型化为了确定重组CAEV载体病毒粒子是否可以被GaLV糖蛋白以及VSV-G糖蛋白假型化,GaLV表达载体、pMYKEF1/env(SEQIDNO72)或VSV-G表达载体、pHGVSV-G(SEQIDNO74)与转移载体质粒和包装质粒一起共转染人293T细胞。转染后48小时,收集含有转染细胞释放的假型病毒颗粒的培养上清,用0.45μm滤膜澄清后用于感染293T靶细胞。感染后一天,用基因组DNA分离试剂盒(Qiagen,HL,Germany)纯化基因组DNA并且进行PCR实验来检测整合的原病毒cDNA。正如预期,CAEV载体(图11中1道)被VSV-G蛋白高效假型化,与MuLV-(图11中3道)和基于HIV-1载体(图11中4道)相当。此外,与HIV-1慢病毒载体系统不一致,本发明的CAEV载体被GaLV包膜成功假型化(图11中2道)。CAEV载体的这种用GaLV包膜假型化的能力可以提供开发临床级慢病毒载体系统的极大优势。MuLV(转染有pEQPAM3、pMFG/lacZ/puro和pHGVSV-G(SEQIDNO74))和HIV-1(转染有pCMVΔR8-2、pHR’/lacZ和pHGVSV-G(SEQIDNO74))载体对照分别显示于3和4道。实施例5CAEV包装细胞系的产生pMGP/RRE(SEQIDNO77)和pHYK/rev(SEQIDNO75)载体都编码用于在真核细胞中筛选的neor基因。为了gag-pol和rev表达载体共转染之后能高效筛选,可用其它抗生素抗性基因如细菌gpt基因替换neor基因来构建另一个CAEVgag-pol表达载体。作为替代,可以使用编码gag、pol和rev基因的单包装质粒系统。为了确定是否能够产生稳定表达CAEV包装蛋白的293T细胞,在选择性培养基中筛选抗生素抗性菌落。从稳定的293T细胞生产重组CAEV载体表明产生用于生产CAEV载体的稳定包装细胞系是可行的。实施例6基于CAEV的载体cDNA在宿主染色体中的整合为了检测转导后CAEV载体cDNA的整合,通过向人293T细胞进行脂质体介导共转染pMGP/REV/RREgag-pol表达质粒、pHGVSV-G(SEQIDNO74)env表达质粒和pCAH/SINd1/hlacZ(SEQIDNO79)转移载体质粒来生产CAEV载体颗粒。作为阳性对照,向人293T细胞共转染pCMVΔR8.2gag-pol表达质粒、pHGVSV-G(SEQIDNO74)env表达质粒和pHR/lacZ转移载体来生产HIV-1载体颗粒。作为阴性对照,仅转染pCAH/SINd1/hlacZ(SEQIDNO79)转移载体质粒。转染后48小时,收集每种转染细胞的培养上清,在8μg/mlpolybrene存在下施加到新鲜的人293T细胞中用于感染。48小时之后,制备每种转导细胞的基因组DNA,限制性酶消化之后进行southern印迹分析。地高辛标记的lacZ探针对于基于HIV-1的转移载体检测到3.15kbBamHI-KpnI片段,以及对于基于CAEV的转移载体和阴性对照检测到1.35kbHindIH-SspI片段。对于阳性对照,使用pCAH/SINd1/hlacZ(SEQIDNO79)转移载体的0.3ng和3ngHindIII-SspIDNA片段。如图12所示,本发明基于CAEV的转移载体以与基于HIV-1的慢病毒转移载体相当的水平被整合。实施例7基因转移至非分裂细胞用DNA合成抑制剂蚜肠霉素处理293T细胞,置于6孔培养板,然后用编码lacZ标记基因的CAEV载体颗粒转导。作为对照,用表达lacZ的MuLV慢病毒载体和HIV-1慢病毒载体平行感染细胞。感染后48小时,为了检测转导效率,通过X-gal染色计数转导lacZ基因的表达。如图14所示,MuLV衍生的载体高效感染未用DNA合成抑制剂处理的细胞。但是,当细胞经DNA合成抑制剂处理被抑制在细胞周期中时,转导效率显著下降。相反,基于CAEV的载体能高效转导非分裂的人细胞以及分裂细胞,其转导水平与基于HIV-1的载体相当。实施例8肌肉细胞的体内转导该实施例中,CAH/SINd1/hlacZ(SEQIDNO79)CAEV载体用于体内转导肌肉细胞。在4μg/mlpolybrene存在下,于小鼠后肢(Beige品系)肌肉注射100μlCAEV载体。两天后处死小鼠,制备经注射的组织用于冷冻切片和用于β-半乳糖苷酶分析。预期结果是CAH/SINd1lacZ(SEQIDNO79)CAEV载体体内高效地转导肌肉细胞。前述说明,包括具体实施方案和实施例,旨在举例说明本发明,而不是作为限制。不偏离本发明的真正精神和范围,可以实施很多其他变化和改进。此处引用的所有公开,包括NCBI数据库中保存的序列、专利和专利申请,经引用其全部内容并入本公开中。参考文献Altschul,S.F.,Gish,W.,Miller,W.,Myers,E.W.,andLipman,D.J.(1990).Basiclocalalignmentsearchtool.JMolBiol215(3),403-10.Altschul,S.F.,Madden,T.L.,Schaffer,A.A.,Zhang,J.,Zhang,Z.,Miller,W.,andLipman,D.J.(1997).GappedBLASTandPSI-BLASTanewgenerationofproteindatabasesearchprograms.NucleicAcidsRes25(17),3389-402.Anderson,M.P.,Rich,D.P.,Gregory,R.J.,Smith,A.E.,andWelsh,M.J.(1991).GenerationofcAMP-acti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CCCTTAAAF322109GAACTGAG........CTGGTCGTGGTTATTATCGGG....GACCGAAGT151200NC_001463TCTGTGCAATACCAGAGCGGCTCTCGCAGCTGGCGCCCAACGTGGGGCCCAF322109CCCGTGCAACACCGGGGCGGTTCTCGCAGCTGGCGCCCAACGTGGGGCTC201250NC_001463GAGGAG............................................AF322109GAGTAGCTTGAGAAGCTCGACTGAGATCTGAATCCAAGAGCGACATCAGA251300NC_001463....AAGAAAAGAAAGC...GGCCCTGAGAACTCGGCTTCTG..AAAAAGAF322109CAGCAAGAAATGAGAGTAATGAGACCGCGAGCTCTGCTGCTGTAAAAAAG301350NC_001463AGGAAGAGGACAAGTTGCTATAGCAACAAGAGAGAAGAAGTAGAGCAAAGAF322109AGGAAGTAG.CGGGTTGCCGAGGCAACTGCTCAGAAGAACCAGGGGAAAG351400NC_001463GTCCAGTGGCT.CGGAAAAAGAGGAACTGAAACTTCGGGGACGCCTGAAGAF322109GGCTTCCAGCAACCTCAAAAGAGGAACCGAGACTTCGGGGACGCCTGAA.401450NC_001463GAGTAAGGTAAGTGACTCTGCTGTACGCGGGGCGAGGCAGAGGTT.TCCTAF322109..GTAAGGTAAGTGACTCTGCTGTACGCGGGGCGAGGCATAGGAGATCCT451500NC_001463TCTAAATT.GAAAGAGAAGTGTTGCTGCGAGAGGTCTTGGTGGTCGAGAAAF322109TCTATTCTAGGAAGAGAAGCGCTGTTCTGGGAGGTCTTGGCGACCGAGAA501550NC_001463TCCTGTACAAAAAAAAGGAGGGATCTCGGTCAGGACCAGGACCCCTGGGAAF322109TCTTGTT...AAATAAGCCAGGATCTCGATCAGGACCAAGACCCCTCAGG551600NC_001463GTAATACAACAGCAACACCGTAAGAAAATCCGCCATGGTGAGTCTAGATAAF322109AGAGGGTATAGACAGCGTGGTAAGAAA.TCCGCCGTGGTGAGTCTAGATA601650NC_001463GAGACATGGCGAGGCAAGTCTCCGGGGGGAAAAGAGATTATCCTGAGCTCAF322109GAGACATGGTGAGGCAGGCCTCCGGAAGGGGAAAGGAGTACCCCGAGCTA651700NC_001463GAAAAATGTATCAAGCATGCATGCAAGATAAAAGTTCGACTCAGAGGGGAAF322109AAAGAATGTCTGAAAAAGGCATGCAAAATAAAAGTAAGGGCTGGGGGGGA701750NC_001463GCACTTGACAGAAGGAAATTGTTTATGGTGCCTTAAAACATTAGATTACAAF322109GCGCCTGACAGAAGGAAATTGTCTCTGGTGTATAAAAACACTAGAGTGTA751800NC_001463TGTTTGAGGACCATAAAGAGGAACCTTGGACAAAAGTAAAATTTAGGACAAF322109TGTATGAGGATTGTAGGGAGGAACCTTGGACCCCAGAAAAATGTAAACAA801850NC_001463ATATGGCAGAAGGTGAAGAATCTAACTCCTGAGGAGAGTAACAAAAAAGAAF322109TTATGGAAAAAGTTGAAGCAGGTAGAGCCTGAGGAGAGTAGCAAAGCAGA851900NC_001463CTTTATGTCTTTGCAGGCCACATTAGCGGGTCTAATGTGTTGCCAAATGGAF322109CTATAACTCGTTAAAAGCAACCTTGGCGGGGATAGTCTGTGTGCAAATGG901950NC_001463GGATGAGACCTGAGACATTGCAAGATGCAATGGCTACAGTAATCATGAAAAF322109GAATGCAGCCCGAGACACTGCAGGATGCGATAGCAACCTTAAACATGAGA9511000NC_001463GATGGGTTACTGGAACAAGAGGAAAAGAAGGAAGACAAAAGAGAAAAGGAAF322109GA........TGAAGTAAAAGGAAAGGAA..AAGCCATCAGAAGAAAAGA10011050NC_001463AGAGAGTGTCTTCCCAATAGTAGTGCAAGCAGCAGGAGGGAGAAGCTGGAAF322109AGGGAATATATCCC..ATATTAGTGCAGGCAGGAGGAGGAAGAGCATGGA10511100NC_001463AAGCAGTAGATTCTGTAATGTTCCAGCAACTGCAAACAGTAGCAATGCAGAF322109GAGCGGTAGAGCCTGCTACCTTTCAGCAGCTCCAAACAGTGGCAATGCAG11011150NC_001463CATGGCCTCGTGTCTGAGGACTTTGAAAGGCAGTTGGCATATTATGCTACAF322109CATGGACTAGTATCAGAAGAATTTGAAAGGCAGCTAGCATACTATGCCAC11511200NC_001463TACCTGGACAAGTAAAGACATACTAGAAGTATTGGCCATGATGCCTGGAAAF322109CACATGGACAAGCAAGGATATCTTAGAAGTATTAGCCATGATGCCAGGAA12011250NC_001463ATAGAGCTCAAAAGGAGTTAATTCAAGGGAAATTAAATGAAGAAGCAGAAAF322109ATAGAGCGCAAAAAGAACTAATACAAGGAAAGTTAAATGAGGAAGCAGAG12511300NC_001463AGGTGGAGAAGGAATAATCCACCACCTCCAGCAGGAGGAGGATTAACAGTAF322109AGATGGAGAAGGCAGAATCCACAACCT......GCGGGCGGGTTAACCGT13011350NC_001463GGATCAAATTATGGGGGTAGGACAAACAAATCAAGCAGCAGCACAAGCTAAF322109GGATCAGATAATGGGGGTAGGACAAACGAATCAGGCAGCGGCACAGGCTA13511400NC_001463ACATGGATCAGGCAAGGCAAATATGCCTGCAATGGGTAATAAATGCATTAAF322109ATATGGATCAAGCAAGACAAATATGCCTACAATGGGTTATAACAGCAATA14011450NC_001463AGAGCAGTAAGACATATGGCGCACAGGCCAGGGAATCCAATGCTAGTAAAAF322109AGAGGAGTTAGGCATATGGCCCATAGACCAGGAAATCCCATGCTGGTAAG14511500NC_001463GCAAAAAACGAATGAGCCATATGAAGATTTTGCAGCAAGACTGCTAGAAGAF322109ACAAAAACCAAATGAGAACTATGAAGAGTTTGCCGCAAGGTTGTTAGAAG15011550NC_001463CAATAGATGCAGAGCCAGTTACACAGCCTATAAAAGATTATCTAAAGCTAAF322109CAGTGGATGCAGAACCCGTTACCCAACCTATAAAAGAATATTTAAAGGTA15511600NC_001463ACACTATCTTATACAAATGCATCAGCAGATTGTCAGAAGCAAATGGATAGAF322109ACTCTGTCTTACACAAATGCAAATTCGGAATGTCAAAAACATATGGACAG16011650NC_001463AACACTAGGACAAAGAGTACAACAAGCTAGTGTAGAAGAAAAAATGCAAGAF322109AGTGTTGGGGCAAAGAGTACAGCAGGCCTCAATAGAAGAAAAAATGCAGG16511700NC_001463CATGTAGAGATGTGGGATCAGAAGGGTTCAAAATGCAATTGTTAGCACAAAF322109CATGCAGGGACATCGGGGGAACAGCATATCAGATGCAGTTGCTTGCACAA17011750NC_001463GCATTAAGGCCAGGAAAAGGAAAAGGGAATGGACAGCCACAAAGGTGTTAAF322109GCCCTCCGTGGCGGAAAAGAAGATGGGAAAAAATCTGTAGGGAAGTGTTA17511800NC_001463CAACTGTGGAAAACCGGGACATCAAGCAAGGCAATGTAGACAAGGAATCAAF322109TAACTGTGGAAGGCCCGGACACAGAGCAAAAGAATGCAGACAAGGCATTA18011850NC_001463TATGTCACAACTGTGGAAAGAGAGGACATATGCAAAAAGAATGCAGAGGAAF322109TATGTCACAACTGTGGAAAAAGAGGGCATATACAGAAAAACTGCA....A18511900NC_001463AAGAGAGACATAAGGGGAAAACAGCAGGGAAACGGGAGGAGGGGGATACGAF322109AC.AGAA....AAGAAGAAAGGAGCAGGGAAACATGAGGAGGGGGCTACG19011950NC_001463TGTGGTGCCGTCCGCTCCTCCTATGGAATAACTTCAGCACCACCTATGGTAF322109TGTGGTGCCGTCCGCACCCCCTATGGAGTAACGCAAGCACCACTAATAGT19512000NC_001463TCAGGTCCGCATAGGTTCCCAGCAGAGGAACTTGTTATTTGATACCGGGGAF322109TAGGGTACAAATAGGGAATCAGGAGAAACAATTATTATTTGACACAGGGG20012050NC_001463CGGACCGAACTATAGTTAGATGGCATGAGGGCTCGGGAAACCCAGCCGGAAF322109CAGATAAAACGATAGTAAGAATGCATGATGGAACAGGGATTCCAAACGGA20512100NC_001463AGGATAAAACTGCAAGGAATAGGAGGAATAGTAGAAGGAGAAAAATGGAAAF322109AGAATAAAATTACAAGGGATAGGAGGAATAGTAGAAGGAGAAAAATGGAA21012150NC_001463TAATGTAGAATTAGAATATAAAGGAGAAACAAGAAAGGGAACAATAGTAGAF322109TAAAGTACCCATGACATATAAGGGAGAAACATCCTGCCCAAGCTTGGTTG21512200NC_001463TGTTACCACAAAGTCCAGTAGAAGTATTAGGACGAGATAACATGGCCCGAAF322109TGCTAAGAGATAGCCCAGTAGAAGTATTGGGAAGAGATAACATGGAAGCA22012250NC_001463TTTGGAATAAAGATAATAATGGCAAATTTAGAGGAAAAAAGAATCCCAATAF322109TTCGGCGTAACCCTAATAATGGCAAATTTAGAAGATAAGAAAATTCCCAC22512300NC_001463TACAAAAGTAAAATTGAAAGAGGGATGTACGGGTCCACATGTCCCACAATAF322109AATACCAGTAGAATTGAAAGAAGGATGTAAAGGGCCACATGTGCCCCAGT23012350NC_001463GGCCATTAACAGAAGAGAAATTAAAAGGTCTAACAGAAATCATAGATAAAAF322109GGCCATTAACAGCAGAGAAATTACAAGGACTAACAGGAATAGTAGAAAAA23512400NC_001463TTAGTGGAAGAAGGAAAACTAGGAAAGGCACCCCCACATTGGACATGTAAAF322109TTACTACAGGAAGGAAAATTGGCAGAGGCCCCAGAGGGATGGACGTGGAA24012450NC_001463TACTCCAATCTTTTGCATAAAAAAGAAATCAGGGAAGTGGAGAATGTTAAAF322109CACGCCCATCTTCTGCATAAAAAAGAAGTCAGGAAAATGGAGAATGTTAA24512500NC_001463TAGATTTCAGAGAATTGAACAAACAGACAGAAGATTTAACAGAAGCGCAGAF322109TAGATTTTAGGGAATTAAATAAGCAAACAGCAGATTTAGCAGAAGCGCAG25012550NC_001463TTAGGACTCCCGCATCCGGGAGGACTACAAAAGAAAAAACATGTTACAATAF322109CTAGGACTGCCACACCCAGGAGGGTTGCAAAGGAAAAAGAATGTAACAAT25512600NC_001463ATTGGACATAGGAGATGCATATTTTACTATACCCCTATATGAACCATATCAF322109TCTGGACATAGGAGATGCATATTTCACAATTCCCTTATACGAGCCCTATC26012650NC_001463GAGAGTACACATGTTTTACTCTATTAAGTCCTAATAATCTAGGACCATGTAF322109AGAAATATACATGCTTCACACTCCTAAGTCCTAACAATTTGGGACCATGT26512700NC_001463AAAAGATACTATTGGAAAGTGCTGCCACAAGGTTGGAAATTGAGTCCATCAF322l09AAAAGGTATTATTGGAAAGTATTACCCCAGGGATGGAAATTGAGCCCAGC27012750NC_001463TGTATATCAATTTACTATGCAGGAGATCTTAGAGGATTGGATACAGCAGCAF322109TGTATATCAATTCACCATGCAAAGGTTGTTAAAAGGATGGATACAACAGC27512800NC_001463ATCCAGAAATTCAATTTGGCATATATATGGATGATATTTACATAGGAAGTAF322109ATAAAAACATACAATTTGGAATATATATGGATGATATCTATATTGGAAGT28012850NC_001463GATTTAGAAATTAAAAAGCATAGAGAAATAGTGAAAGATTTAGCCAATTAAF322109GATCTAACGATAGCCCAACATAGGAAGATAATAGAAGAATTAGCCTCATT28512900NC_001463TATTGCCCAATATGGATTCACTCTGCCAGAAGAGAAGAGACAAAAGGGATAF322109TATAGAACAATTTGGGTTTACATTACCAGAAGATAAGAGACAAGAGGGCT29012950NC_001463ATCCAGCAAAATGGCTAGGATTTGAACTACACCCGCAGACCTGGAAATTTAF322109ATCCAGCAAAATGGCTAGGATTCGAGCTACATCCAGAAAAATGGAAATAT29513000NC_001463CAGAAGCATACATTACCTGAATTAACAAAGGGAACAATAACATTAAATAAAF322109CAAAAGCATAAATTGCCGGAATTACAAGAGGGGGTAATAACCCTGAACAA30013050NC_001463ATTACAGAAATTAGTAGGAGAATTAGTATGGAGACAATCCATAATTGGGAAF322109ATTACAGAAGATAGTAGGGGAATTAGTGTGGAGACAATCCTTGATAGGAA30513100NC_001463AAAGCATTCCTAACATTCTGAAATTAATGGAAGGAGATAGAGAATTACAAAF322109AGAGCATCCCCAATATCATAAAATTAATGGAAGGAGATCGCGCATTACAA31013150NC_001463AGTGAAAGAAAAATTGAAGAAGTACATGTGAAAGAATGGGAAGCATGTAGAF322109AGTGAAAGGAAAATAGAAAGAATACATGTACAAGAATGGGAAGCATGTCA31513200NC_001463GAAAAAATTAGAAGAAATGGAAGGAAATTATTATAATAAAGACAAAGATGAF322109AAAGAAATTAGATGAAATGGTAGGAAATTATTACAGAGAAGAAGAAGATA32013250NC_001463TCTATGGACAATTGGCTTGGGGAGACAAAGCTATAGAATATATAGTGTATAF322109TCTATGGACAAATAACTTGGGGGGATAAGGCAATAAAATACATAGTATTC32513300NC_001463CAGGAGAAAGGGAAACCATTATGGGTAAATGTGGTTCACAATATAAAGAAAF322109CAAAGGAAAGGGGAACCCCTATGGGTAAATGTAGTACATGACATAAAAAA33013350NC_001463CCTAAGCATCCCGCAACAGGTTATTAAAGCAGCGCAAAAATTAACCCAAGAF322109TTTGAGTCTCCCACAGCAAGTGATAAAAGCAGCACAGAAATTAACCCAGG33513400NC_001463AAGTCATCATTAGGACAGGAAAAATACCATGGATATTGTTGCCAGGGAAAAF322109AAGTAATCATAAGAACAGGAAAAATCCCATGGCTGCTACTACCAGGAAGA34013450NC_001463GAAGAAGATTGGAGACTAGAATTGCAATTAGGGAACATCACATGGATGCCAF322109GAAGAAGACTGGAGATTAGAACTGCAGGTAGGGAACATCACGTGGATGCC34513500NC_00l463AAAATTTTGGTCCTGTTATCGAGGA.CATACAAGATGGAGAAAAAGAAATAF322109ATCATTTTGGTCATGTTATCGAGGAGCACCCAAG.TGGAAAAGAAGGAAC35013550NC_001463ATAATAGAAGAAGTAGTAGAAGGGCCTACATATTATACAGATGGAGGAAAAF322109ATAGTGGCAGCAGTGGTAGATGGACCGACATATTATACAGATGGGGGAAA35513600NC_001463AAAGAATAAAGTAGGAAGTCTAGGGTTCATAGTATCAACAGGGGAAAAATAF322109GAAAAACGCACAGGGAAGCTTTGGCTTCATCTCCCCAACAGGAGAAAAGT36013650NC_001463TTAGAAAGCATGAAGAGGGCACAAACCAGCAACTAGAATTAAGAGCCATAAF322109TCAGAAGGCATGAAGATGGAACTAATCAGGTATTAGAATTAAGGGCAATA36513700NC_001463GAGGAAGCTCTAAAACAAGGGCCTCAAACAATGAATTTAGTAACAGATAGAF322109GAAGATCCATGTAAACAAGGACCTGAAAGCATGAACATTGTAACTGACAG37013750NC_001463TAGATATGCATTTGAATTTTTATTAAGAAATTGGGATGAAGAAGTAATAAAF322109CAGGTATGCTTATGAATTCATGCTCCGAAACTGGGATGAACAGGTCATAA37513800NC_00143AGAATCCAATTCAAGCAAGAATTATGGAAATTGCCCACAAGAAAGATAGGAF322109GAAACCCCATTCAGGCAAGAATCATGGCAGAAGTGCACAAGAAAAAGCAG38013850NC_001463ATAGGAGTGCATTGGGTGCCAGGACATAAAGGGATTCCCCAAAATGAAGAAF322109GTAGGAATACACTGGGTGCCAGGGCATAAAGGAATACCTCAGAATGAAGA38513900NC_001463AATAGACAAATATATTTCGGAAATATTTCTTGCAAAAGAAGGAGAAGGAAAF322109GATAGACCAGTACATATCAGAAGTATTCTTAGCACGAGAAGGAACAGGGA39013950NC_001463TTCTCCCAAAAAGAGAAGAGGATGCAGGGTATGATTTAATATGCCCAGAAAF322109TATGTGAAAAAAGGAAGGAAGATGCTGGATATGATTTATTATGCCCGCAT39514000NC_001463GAGGTTACCATAGAGCCAGGACAAGTGAAATGCATCCCCATAGAGCTAAGAF322109GAGGTAATACTTAAACCCCAAGAAGTAAAACGGATCCCAATAGACCTAAA40014050NC_001463ATTAAATTTAAAGAAATCACAATGGGCTATGATTGCTACAAAAAGCAGCAAF322109ATTAAAATTGAAAGAAAAGCAATGGGCCATGATAAGTGGGAAAAGTAGCG40514100NC_001463TGGCTGCCAAAGGAGTGTTCACACAAGGAGGAATCATAGACTCAGGATATAF322109TTGCAGCAAAAGGAATATTTGTACAAGGAGGCATAATAGATTCAGGGTAT41014150NC_001463CAGGGACAAATACAGGTAATAATGTATAATAGCAATAAAATAGCAGTAGTAF322109CAGGGACAAGTACAAGTCATCCTATATAATAGTAATAAGATAGAGGTCAA41514200NC_001463CATACCCCAAGGGAGAAAATTTGCACAATTAATATTAATGGATAAAAAGCAF322109AATACCACAAGGCAGGAAATTTGCCCAATTAATATTAATGAACTTACAAC42014250NC_001463ATGGAAAATTGGAACCCTGGGGGGAAAGCAGAAAAACAGAAAGGGGAGAAAF322109ATGAAGAATTAGAAGAATGGGGAAAGGAAAGAAAAACAGAAAGAGGAACA42514300NC_001463AAAGGATTTGGGTCTACAGGAATGTATTGGATAGAAAATATTCCTCTGGCAF322109AAAGGATTTGGGTCTACAGGAGCATTTTGGATAGAGAATATTCCCCAAGC43014350NC_001463AGAGGAAGACCACACAAAATGGCATCAAGATGCCCGATCATTGCATCTAGAF322109AGAGGAAGAACATTACAAATGGCATCAAGATGCTAGATCTCTGCAGCTAG43514400NC_001463AATTTGAAATTCCAAGAACAGCAGCAGAAGACATAGTAAATCAATGTGAAAF322109AATTCAAGATACCTAGAGCAGCAGCAGAAGACATTATACAGCACTGTGAG44014450NC_001463ATATGCAAAGAAGCGAGGACACCTGCAGTAATTAGAGGCGGAAACAAAAGAF322109GTATGTCAAGAAGGCAAACCCGCAGCGATCACGAGAGGGGGAAATAAAAG44514500NC_001463GGGGGTAAATCATTGGCAAGTGGATTATACCCATTATGAAAATATCATACAF322109AGGAATAGATCATTGGCAGGTAGACTATACACATTACAAAGAACACATAA45014550NC_001463TATTAGTATGGGTAGAAACAAATTCAGGACTAATATATGCAGAAAAAGTAAF322109TATTAGTATGGGTAGAGACTAATTCAGGATTAATATTTGCAGAGAAAGTA45514600NC_001463AAAGGAGAATCAGGGCAAGAATTCAGAATAAAAGTGATGCATTGGTATGCAF322109AAAGGAGAATCAGGACAAGAATTTAGGATGCAGACATTGAAATGGTATGC46014650NC_001463ATTATTTGGTCCAGAGTCATTGCAGTCAGACAATGGACCTGCATTTGCAGAF322109TTTGTTTCAACCAAAATCAGTGCAATCAGATAATGGGACAGCCTTCACAG46514700NC_001463CAGAGCCCACACAGCTGTTAATGCAATACCTAGGAGTAAAACACACAACAAF322109CTGAGGCTACGCAGCATCTAATGAAGTATTTAGGGATTCAGCACACTACG47014750NC_001463GGCATACCTTGGAATCCACAGTCTCAGGCTATAGTAGAAAGGGCACATCAAF322109GGTATTCCGTGGAACCCCCAGTCACAAAGTTTAGTAGAAAGAGCTCATCA47514800NC_001463ACTATTGAAAAGCACTTTAAAGAAGTTCCAGCCACAATTTGTCGCTGTAGAF322109AACATTAAAACACATGTTAGAAAAATTAGAACCACAATTTGTGGCCCTAC48014850NC_001463AATCAGCCATAGCAGCAGCCCTAGTCGCCATAAATATAAAAAGAAAGGGTAF322109AGTCTGCCATCGCAGCCACTCTAGTTGCGCTCAATATAAAAAGAAAGGGT48514900NC_001463GGGCTGGGGACAAGCCCTATGGATATTTTTATATATAATAAAGAACAGAAAF322109GGACTAGGGGCAAGCCCTATGGATATTTACATATATAATAAGGAGCAACA49014950NC_001463AAGAATAAATAATAAATATAATAAAAATTCTCAAAAAATTCAATTCTGTTAF322109AAGACAACAAGATAATAGTAATAAATTAATTCAGAAAA...AATTTTGTT49515000NC_001463ATTACAGAATAAGGAAAAGAGGACATC.AGGAGAGTGGAAAGGACCAACCAF322109ATTACAGGATCAGAAAAAGAGGCCATCCAGGAGAGTGGAACGGCCCAACT50015050NC_001463CAGGTACTGTGGAAAGGGGAAGGAGCCAATTGTGGTAAAGGATATAGAAAAF322109GAGGTACTGTGGGAAGGGGAAGGAGCCA.TAGTAGTTAAAGACAAAGAAA50515100NC_001463GTGAAAAGTATTTAGTAATACCTTACAAAGATGCAAAATTCATCCCGCCAAF322109GTGATAGATATCTAGTCATCCCATATAAAGATGCAAAATTTATTCCGCCA51015150NC_001463CCAACAAAAGAAAAGGAATAAAAAACCTGGACCAGAATTACCCTTAGCACAF322109CCGTCGGAACAGAAGGGATAGAAGAATAGGTCCAGAATTGCCTTTATCTT51515200NC_001463TATGGATACATATAGCAGAAAGCATTAATGGGGATAGCTCATGGTACATAAF322109TATGGACTTATACAGCATACAGCATAAATAAAGATCCCGCATGGTATACA52015250NC_001463ACAATGAGACTGCAACAGATGATGTGGGGAAAAAGAGGAAATAAGTTACAAF322109ACCCTAAGACTGCAGCAAATGATGTGGCATAGGAGGGGAAATAAATTGAC52515300NC_001463ATATAAGAATGAAGACAGGGAATATGAAAATTGGGAAATTACATCATGGGAF322109ATATGTCAGGGAAAATGCACAGTACGAGGAGTGGGAAATGACCTCGTATG53015350NC_001463GATGGAAAATGCACCTAAGGAGAGTGAAACAATGGATACAAGACAACAGGAF322109AGTGGAGGATAAGAATGAGAAGGGACAAAACAAAAAGTCATC.CAAGAGG53515400NC_001463AGAGGAAGC.CCATGGCAGTACAAAGTAGGAGGAACATGGAAAAGTATAGAF322109GCATACTTCGCCATGGCAATATCGGAGACAGGATGGATGGAAGGATGTGG54015450NC_001463GAGTGTGGTTCCTGCAAGCAGGAGATTACAGAAAGGTAGACAGGCACTTCAF322109GAACGTGGTTCCTACAGCCAGGGGACTATAGAAAGGCGGATCAGCAGTTC54515500NC_001463TGGTGGGCATGGAGGATACTGATATGTTCCTGCAGGAAAGAAAAGTTTGAAF322109TGGTTCGCTTGGAGAATAGTGTCGTGTTCATGTAAAAAGGAAGGATTTAA55015550NC_001463TATAAGAGAATTTATGAGAGGAAGACATAGATGGGATTTGTGCAAATCCTAF322109CATAAGAGAATTTATGCTAGGTACCCATAGATGGGATTTGTGTAAGTCGT55515600NC_001463GTGCTCAAGGAGAAGTAGTAAAGCATACTAGAACAAAAAGTCTGGAAAGAAF322109GTTGCCAGGGTGAAGTAGTAAAGAGAACACAACCCTACACCTTGCAAAGG56015650NC_001463CTAGTACTGCTACAGATGGTAGAACAGCATGTGTTTCAAGTATTGCCATTAF322109CTCACGTGGCTTAAATTAACAGAAGACCATGTATTTCAAGTAATGCCCTT56515700NC_001463GTGGAGAGCCAGGAGAAGTAGTACAACAGATTTCCCATGGTGCAGGGACAAF322109GTGGAGAGCTCGCAAAGGGATTACCATAGACTTTCCCTGGTGCAGGGACA57015750NC_001463CAACGGGATACACGCATGCGTGGTCTGTCCAGGAGTGCTGGTTGATGGAAAF322109CAAAAGGATTCCTGGAGCCGTGGACAACGCAAGAGTGTTGGCAAATAGAG57515800NC_001463TATCTCTTAGAGGATGAGTGAAGAACTGCCTCAAAGAAGGGAGACACATCAF322109TATCCCTTGGAGGATGAGTGAGGAAACCCCAGCAGGAAGAGAACCGACTG58015850NC_001453CAGAAGAACT.TGTAAGGAACGTACGGGAAAGAGAAAGGGATACATGGCAAF322109CAGAGGAAATATTTGAGCAA.......GAAGCAGAAAGT......TGGAA58515900NC_001463ATGGACAAGCATCAGAGTACCTGCGGAAATACTGCAAAGATGGCTTGCTAAF322109GAGAACAAGCGTGCGAGTCCCAAATGACATATTACAAAGATGGCTAGCAA59015950NC_001463TGCTTAGGTCAGGCAGAAATAGAAAGAAAGTGTATAGAGAAATGCAAAAAAF322109TGCTTAGGCAAAGAGGAAATAGAAAGAAAGTGCTTAGGGAAATGCAAAAA59516000NC_001463TGGATGTGGATACATCCCAAGGCGCCTGTGATTAGGGCCTGTGGATGCAGAF322109TGGGCATGGAGGAATCCCACGGCGCGGGTGATTCGGCCGTGTGGATGTCG60016050NC_001463ACTATGTAACCCGGGGTGGGGAACATAATCAAGGGAATAATAAATGCAAAAF322109GCTATGTAACCCCGGCTGGGGGAG.TAATTAAT..CATAATAAA.GCAAA60516100NC_001463TAAATGTAACTAACAAGTAGCAAAAGTGTCTGTGTTAGATGGATGCTGGGAF322109T...TGTAAC................................ATGCTGTG61016150NC_001463GCCAGATACATGCGCTTAACTGGGAAGGAAAACTGGGTTGAAGTAACCATAF322109TC.....A..............GG.........TGTCTTGCAGGAA...T61516200NC_001463GGACGGAGAGAAGGAAAGGAAAAGAGAAGGTTTCACTGCGGGACAGCAAGAF322109GG.CGGAGATAAGAAAAG..AA.GCAAAGGAGCCACT.....AATCCAGG62016250NC_001463GTAAGTATCAACCCCAGGTAAGTAAGCAAATAGGGAACAGAAATACTAACAF322109GTAAGTATAAAAAACAGGTAAGTA.........G......AA....TAAC62516300NC_001463CCATGCTTTGCCTATAAAGGGATATTCCTATGGAGGATATCACTAACAATAF322109..............TATAGTTATATT..........A.....CTAACAGT63016350NC_001463GTGGATATTGCTAGGGATAAATATGTGTGTCAGTGCAGAGGATTACATAAAF322109AAGAGCAGCACTAGG.......A...........GCAGAA...TACATAA63516400NC_001463CACTAATATCAGATCCCTATGGGTTCTCACCCATAAAAAATGTGTCTGGGAF322109CCATAATATCAGACCCATATGGGTTCTCTCCCGTGAGAAATGTGTCAGGA64016450NC_001463GTACCAGTGACTTGTGTAACAAAAGAATTCGCAAAATGGGGATGTCAACCAF322109GTACCTGTAACTTGTGTGACAAAAGAATTTAGTAAGTGGGGATGTCAGCC64516500NC_001463ACTAGGAGCGTACCCTGATCCAGAAATAGAATACAGAAATGTGAGTCAGGAF322109AATAGGAGCCTACCCAGACCCAGACTTAGAATACAGAAATATAAGTAAAG65016550NC_001463AAGTAGTGAAAGAAGTATATCAAGAGAATTGGCCATGGAATACATATCATAF322109AAATATTAGAGGAAGTATATCAACAAGACTGGCCGTGGAATACTTATCAT65516600NC_001463TGGCCTCTCTGGCAAATGGAGAATGTTAGGTACTGGTTAAAAGAAAATATAF322109TGGCCATTATGGCAAATGGATAATGTAGTACAATGGGCAAGGCAAAATTT66016650NC_001463GCAAGAAAATCAACAGAGAAAAAATAATACAAAAGAGGGTATAGAGGAATAF322109ACAGGATAACCGCAAG.GAAAAAAG...........GGACCTGGCAGACC66516700NC_001463TATTAGCAGGAACTATAAGGGGAAGATTCTGTGTACCATACCCATTTGCCAF322109TATTAGCAGGAAAAATAAGGGGAAGATTCTGTGTACCCTACCCATTTGCG67016750NC_001463TTGTTAAAATGCACAAAGTGGTGCTGGTATACAGCGGCCATAAA..CAACAF322109CTCCTGGAGTGCATGGAATGGTGCTGGTGGGTTAAGAACACTAATGCAGG67516800NC_001463GAGTCA.GGAAAAGCAGGAAAAATAAAAATAAATTGCACAGAAGCAAGAGAF322109GGGGTATGGAGAAGCAG..A.CATAAGAATAAATTGCTCAAGGGCAAGAG68016850NC_001463CAGTCTCCTGTACAGAGGACATGCCATTAGCCTCAATACAAAGAGCATATAF322109CAGTGAGCTGCACAAGTGAAATGCCCTTAGCATCCCTACAGAGGGTATAT68516900NC_001463TGGGATGAGAAAGACAGAGAGAGCATGGCCTTTATGAATATCAAAGCATGAF322109TGGGAAAAGGAGGAACGAAAAAACATGGAGAAAATGACCATCAAACCTTG69016950NC_001463TGATAGCAACCTAAGGTGTCAGAAAAGACCTGGAGGGTGTATGGAAGGATAF322109CAATAAAAATTTGGAATGCAAGAACAGAA..G.GGGATGCGCAGAAGGGT69517000NC_001463ACCCTATCCCAGTAGGAGCAGAAATAATCCCTGAAAGTATGAAATACCTAAF322109ATCCAGTACCTCCCAAGGCAGAGTTATTCCCTCCAGCGTTTCAGGATTTA70017050NC_001463AGGGGAGCAAAGAGTCAG..TATGGGGGAATAAAAGATAAGAATGGAGAAAF322109CAGCCA..AAAGGGTACGCATATGGGGCACTTAGAG...GGAACAGCAAA70517100NC_001463TTAAAATTACCATTAACATTAAGAGTGTGGGTAAAATTAGCAAATGTGTCAF322109TTTCCACAAAGAGTGTCGCTAAGAACATGGGTGAAAATAGCTAACCTGAC71017150NC_001463AGAATGGGTAAATGGGACACCCCCGGATTGGCAAGACAGAATTAACGGATAF322109AGGATGGGAAAAAGGAAAGCCAGCAGAATGGT......GGAATACCAG..71517200NC_001463CCAAAGGAATAAATGGGACGCTCTGGGGAGAGCTTAACAGTATGCATCACAF322109CCAACAGGTTCATTGGTTTGATACCACGCCACAATATCATTTAGGAT...72017250NC_001463CTAGGATTTGCCCTTAGCCAGAACGGCAAATGGTGTAACTACACCGGGGAAF322109.ATGTATTATCCCGAGCGCCTGAGAACAGGAGTTGTAATTTCACAGGGGA72517300NC_001463AATAAAATTAGGGCAAGAAACATTCCAATATCATTACAAGCCAAACTGGAAF322109AATACGAATAGGGCAACATCAGTTTGAGTATAATTACACCCTGACAAAGA73017350NC_001463ACTGTACC...GGGAATTGGACGCAATATCCGGTGTGGCAAGTGATTAGAAF322109ATTGCACAAAGGAGAAGTGGAAAGAGTACCCCATGTGGCATGTCTGGAGG73517400NC_001463AACCTGGATATGGTGGAACATATGACAGGAGAATGTGTGCAGAGACCACAAF322109CATTTAGATCAAAATGAGCACTTATCTAGCATATGTTTCAAAAGACCGAG74017450NC_001463AAGGCACAATATAACAGTAGGAAATGGAACCATAACAGGGAATTGCAGTAAF322109AAGAAATGCAACACAAATAGGGAACAGTACACTGCAAGGGCAATGTAATA74517500NC_001463CAACAAACTGGGATGGATGTAATTGCTCACGATCAGGAAACTACCTATATAF322109GAAGTAATTGGACAGGATGCCACTGCAATGAGACAGGGATAAAC..AC..75017550NC_001463AACAGCTCTGAGGGAGGATTGTTATTAATTCTGTGCAGACAAAACAGCACAF322109AACA.............................TGGAGAATAAATGGCAC75517600NC_001463CCTAACAAGGATCCTGGGAACAAATACAAATTGGACAACTATGTGGGGAAAF322109....AAAGGGAGC.TT..ATCTCTTA..AATAGCACTAAT.....GGAAA76017650NC_001463TATACAAAAATTGTTCAGGATGCGAGAATGCAACATTAGACAACACAGGAAF322109CATCATGGTCTTGTT....ATGCTGGAACACAACAGTGG......CAGGG76517700NC_001463GAAGGAACCTTAGGAGGTGTAGCTAATAAGAACTGTAGCTTGCCTCATAAAF322109GTA.......TATGAGAGTCAGCTAA....A.GTGGAATGAGAGTCTTAA77017750NC_001463AAATGAGAGCAACAAGTGGACTTGTGCCCCAAGACAAAGAGATGGAAAAAAF322109AGACGGAGACTATGGGCTCTGTTTTAATTCAACAAACAGGAATTGTACTA77517800NC_001463CAGATTC.GCTATACATAGCAGGAGGAAAAAAGTTTTGGACACGAATTAAAF322109GAAATGGAGCTCGGCACTATGTAAACAAGAGAGTGATAAAAAACGAC.AC78017850NC_001463GGCCCAATTCAGCTGTGAAAGTAACATAGGACAATTAGATGGAATGTTGCAF322109AGCAGATCATAATTGTGATAGCAGCATATCAGCAATAGATGGAATGGTAC78517900NC_001463ATCAGCAAATACTATTGCAAAAATATCAAGTAATTAAGGTAAGAGCTTATAF322109ATCAACAAATATTACTGCAAAGGTATCAAGTAATTAGAGTAAGAGCTTAC79017950NC_001463ACATATGGGGTGATAGAAATGCCAGAAAACTATGCAAAAACAAGAATCATAF322109ACATACGGAGTGATTGATATGCCAGACAATTATG.AGACCCTACCAGGA.79518000NC_001463AAACAGGAAAAAAAGAGAACTCAGCCACAAGAGGAAGAAGAGAGGCGTTGAF322109....AGGAGAAGGAGAGATCTCGCAAAGGCCAGGAAAAAGAGGGGCGTGG80018050NC_001463GCTTGGTCATTATGCTAGTTATCATGGCAATAGTAGCTGCCGCAGGGGCTAF322109GCCTGGTCATCATGTTAGCTATCATGGCCATAGTGGCTGCTGCAGGAGCA80518100NC_001463TCTCTGGGAGTCGCAAACGCGATTCAGCAGTCTTACACTAAGGCAGCTGTAF322109TCTCTGGGAGTCGCGAACGCGATTCAGCAGTCCTACACCAGGGACGCTGT81018150NC_001463CCAGACCCTTGCTAATGCAACTGCTGCACAGCAGGATGTGTTAGAGGCAAAF322109CCAGACTCTTGCTAACGCGACTGCTGTGCAACAGCAGGTGTTAGAGGCGT81518200NC_001463CCTATGCCATGGTACAGCATGTGGCTAAAGGCGTACGAATCTTGGAAGCTAF322109CCTATGCCATGATACAGCATGTGGCTAAGGGAATACGCATCCTTGAAGCA82018250NC_001463CGAGTGGCTCGAGTGGAAGCTATCACAGATAGAATAATGCTATACCAAGAAF322109CGCGTGGCGAGAATGGAAGTTATGATGGATAGAATGATGTTATATCAGGA82518300NC_001463ATTGGATTGTTGGCACTATCATCAATACTGTATAACCTCTACAAAAACAGAF322109AGTAGACTGCTGGCATTATCACCAATATTGTGTAACCTCTACAAGAGCAG83018350NC_001463AAGTAGCAAAATATATCAATTGGACGAGGTTTAAGGATAATTGCACATGGAF322109ACATAGTGAATTACATTAATTGGACAAGGTTTAAAGATAATTGCACATGG83518400NC_001463CAGCAGTGGGAGAGAGGATTACAGGGGTATGATACAAACTTAACAATACTAF322109CAAGAGTGGGAAAGGGAGATAAGTGCGCATGAAGGAAACATCACTATATT84018450NC_001463GTTAAAGGAATCAGCAGCAATGACACAACTAGCAGAAGAGCAAGCAAGGAAF322109ACTCAAAGAATCAGCAAGGATAACACAATTAGCACAACAAAAGGTACAAA84518500NC_001463GGATACCAGAAGTATGGGAAAGTTTAAAAGACGTCTTTGATTGGTCAGGAAF322109GAATACCAGATGTGTGGACAGCACTAAGGGAGTCACTAGGATGGACACAA85018550NC_001463TGGTTCTCATGGCTAAAGTATATTCCTATTATAGTAGTAGGATTATTAGGAF322109TGGCTGGCTTGGATAAAATACCTTCCCATAATAGTAGTAGGGATATTAGG85518600NC_001463ATGCATTCTGATAAGAGCTGTGATATGTGTATGTCAACCTCTTGTGCAGAAF322109ATGCATAATCATAAGAATAATGTTGTGTGTAGTACAACCAGTTCTTCAGA86018650NC_001463TATACAGAACTCTAAGTACCCCGACATACCAACGGGTCACAGTCATCATGAF322109TTTACAGAACCTTGACTCAGACCAGGTATCAACAAGTCAACTTGGTGATG86518700NC_001463GAAACAAGAGCAGACGTCGCAGGAGAAAATCAGGATTTTGGC...GATGGAF322109GAGACCCGGGTGCAACTAGAAGAAGAAGAAGAAGAAGACGGAAGGGATGG87018750NC_001463CTTAGAGGAATCAGACAA...CAGCGAAACAAGCGAAAGAGTGACAGTACAF322109TGGAGATGGCTCAGAGAGATGCAGCGATCCCGACAACAAAGG...AATTA87518800NC_001463AGAAAGCTTGGAGCCGTGCCTGGGAGCTTTGGCAGAACTCACCCTGGAAGAF322109TGAACGCCTGGAGGAGAGCTTGGGTGACTTGGAGAAACTCACCTTGGCAG88018850NC_001463GAGCCATGGAAAAGGGGCCTGCTGAGGCTGCTCGTCCTTCCGCTGACGATAF322109AACACATGGAAGAATGTGGTGGTGGCGCCGTTGGTGATTCCGCTGACAAT88518900NC_001463GGGAATCTGGATAAATGGATGGCTTGGAGAACACCACAAAAATAAAAAAAAF322109CAGAATTTGGCTCCTTGGAGAGAATGGAGAGAACCCCTAAAAGAAAAATA89018950NC_001463GAAAGGGTG.ACTGTGAGACATGGGCTAAAGAGGACTAATAACAAGCTAGAF322109AAAAGGGTGGACTGTGAGGACTGTG......AGGCCTAGGAGCGAGATAG89519000NC_001463GCCAAATTCCTGTAAATCACTTGGGGGGTTATAAGAAAAGCAAGTTCACTAF322109...AAACTTATAGGCCTCTCTTCCCGG.........AAAGCTAACTCACT90019050NC_001463ATGACAAAGCAAAATGTAAAGGCCAAATTCCTGTAAATCACTTGGGGGGTAF322109GTG........AGAGGAATAG..CAAGTCACAGTGA..CACT.....GCT90519100NC_001463TATAAGAAAAGCAAGTTCACTATGACAAAGCAAAATGTAACCGCAAG...AF322109AATTGTACCCGCAA...CCCTGAGATCATGCAAACCACAATCCTGAGATT91019150NC_001463.TGCTGACAGATGTAACAGCTGACATATCAGCTGATGCTTGCTCATGCTGAF322109ATGCTGACATGTGTAACAGCTGATGCCTCAGCTGATGCTTGCTCATGCTG91519200NC_001463ACACTGTAGCTCTGAGCTGTATATAAGGAGAAGCTTGCTGCTTGC.ACTTAF322109ACAATGTAACTAGGAGCTCTATATAAACAGAGCCCTAGAGCTTGCTACTT92019250NC_001463CAGAGTTCTAGGAGAGTCCC...........TCCT.AGTCTCTCCTCTCCAF322109CAGAGTGCTCTGAGGAGCTCGAAGGAAAGAGTCCTCAGCCTCTCCTCTCC92519300NC_001463GAGGAGGTACCGAGACCTCAAAATAAAGGAGTGATTGCCTTACTGCCGA.AF322109GAGGAGCTTCGG....CTCATAATAAAGGAGTGCTTGCTTCA..ACAGAA表2PileUpMSF759TypeNCheck1376..NameNC_001463(gag720bp)(SEQIDN03)Len759Check9060Weight0NameAF322109(gag720bp)(SEQIDN04)Len759Check2316Weight0//150NC_001463(gag720bp)ATGGTGAGTCTAGATAGAGACATGGCGAGGCAAGTCTCCGGGGGGAAAAGAF322109(gag720bp).....................ATGGTGAGGCAGGCCTCCGGAAGGGGAAA51100NC_001463(gag720bp)AGATTATCCTGAGCTCGAAAAATGTATCAAGCATGCATGCAAGATAAAAGAF322109(gag720bp)GGAGTACCCCGAGCTAAAAGAATGTCTGAAAAAGGCATGCAAAATAAAAG101150NC_001463(gag720bp)TTCGACTCAGAGGGGAGCACTTGACAGAAGGAAATTGTTTATGGTGCCTTAF322109(gag720bp)TAAGGGCTGGGGGGGAGCGCCTGACAGAAGGAAATTGTCTCTGGTGTATA151200NC_001463(gag720bp)AAAACATTAGATTACATGTTTGAGGACCATAAAGAGGAACCTTGGACAAAAF322109(gag720bp)AAAACACTAGAGTGTATGTATGAGGATTGTAGGGAGGAACCTTGGACCCC201250NC_001463(gag720bp)AGTAAAATTTAGGACAATATGGCAGAAGGTGAAGAATCTAACTCCTGAGGAF322109(gag720bp)AGAAAAATGTAAACAATTATGGAAAAAGTTGAAGCAGGTAGAGCCTGAGG251300NC_001463(gag720bp)AGAGTAACAAAAAAGACTTTATGTCTTTGCAGGCCACATTAGCGGGTCTAAF322109(gag720bp)AGAGTAGCAAAGCAGACTATAACTCGTTAAAAGCAACCTTGGCGGGGATA301350NC_001463(ga9720bp)ATGTGTTGCCAAATGGGGATGAGACCTGAGACATTGCAAGATGCAATGGCAF322109(9ag720bp)GTCTGTGTGCAAATGGGAATGCAGCCCGAGACACTGCAGGATGCGATAGC351400NC_001463(gag720bp)TACAGTAATCATGAAAGATGGGTTACTGGAACAAGAGGAAAAGAAGGAAGAF322109(gag720bp)AACCTTAAACATGAGAGATGAAGT........AAAAGGAAAGGAA..AAG401450NC_001463(gag720bp)ACAAAAGAGAAAAGGAAGAGAGTGTCTTCCCAATAGTAGTGCAAGCAGCAAF322109(gag720bp)CCATCAGAAGAAAAGAAGGGAATATAT..CCCATATTAGTGCAGGCAGGA451500NC_001463(gag720bp)GGAGGGAGAAGCTGGAAAGCAGTAGATTCTGTAATGTTCCAGCAACTGCAAF322109(gag720bp)GGAGGAAGAGCATGGAGAGCGGTAGAGCCTGCTACCTTTCAGCAGCTCCA501550NC_001463(gag720bp)AACAGTAGCAATGCAGCATGGCCTCGTGTCTGAGGACTTTGAAAGGCAGTAF322109(gag720bp)AACAGTGGCAATGCAGCATGGACTAGTATCAGAAGAATTTGAAAGGCAGC551600NC_001463(gag720bp)TGGCATATTATGCTACTACCTGGACAAGTAAAGACATACTAGAAGTATTGAF322109(gag720bp)TAGCATACTATGCCACCACATGGACAAGCAAGGATATCTTAGAAGTATTA601650NC_001463(gag720bp)GCCATGATGCCTGGAAATAGAGCTCAAAAGGAGTTAATTCAAGGGAAATTAF322109(gag720bp)GCCATGATGCCAGGAAATAGAGCGCAAAAAGAACTAATACAAGGAAAGTT651700NC_001463(gag720bp)AAATGAAGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCTCCAGCAGAF322109(gag720bp)AAATGAGGAAGCAGAGAGATGGAGAAGGCAGAATCCACAACCTGCGG...701750NC_001463(gag720bp)GAGGAGGATTAACAGTGGAT..............................AF322109(gag720bp)...GCGGGTTAACCGTGGATCAGATAATGGGGGTAGGACAAACGAATCAG751NC_001463(gag720bp).........AF322109(gag720bp)GCAGCGGCAPileUpMSF1347TypeNCheck2008..NameNC_001463(gag)(SEQIDNO5)Len1347Check6959Weight0NameAF322109(gag)(SEQIDNO6)Len1347Check5049Weight0//150NC_001463(gag)ATGGTGAGTCTAGATAGAGACATGGCGAGGCAAGTCTCCGGGGGGAAAAGAF322109(gag).....................ATGGTGAGGCAGGCCTCCGGAAGGGGAAA51100NC_001463(gag)AGATTATCCTGAGCTCGAAAAATGTATCAAGCATGCATGCAAGATAAAAGAF322109(gag)GGAGTACCCCGAGCTAAAAGAATGTCTGAAAAAGGCATGCAAAATAAAAG101150NC_001463(gag)TTCGACTCAGAGGGGAGCACTTGACAGAAGGAAATTGTTTATGGTGCCTTAF322109(gag)TAAGGGCTGGGGGGGAGCGCCTGACAGAAGGAAATTGTCTCTGGTGTATA151200NC_001463(gag)AAAACATTAGATTACATGTTTGAGGACCATAAAGAGGAACCTTGGACAAAAF322109(gag)AAAACACTAGAGTGTATGTATGAGGATTGTAGGGAGGAACCTTGGACCCC201250NC_001463(gag)AGTAAAATTTAGGACAATATGGCAGAAGGTGAAGAATCTAACTCCTGAGGAF322109(gag)AGAAAAATGTAAACAATTATGGAAAAAGTTGAAGCAGGTAGAGCCTGAGG251300NC_001463(gag)AGAGTAACAAAAAAGACTTTATGTCTTTGCAGGCCACATTAGCGGGTCTAAF322109(gag)AGAGTAGCAAAGCAGACTATAACTCGTTAAAAGCAACCTTGGCGGGGATA301350NC_001463(gag)ATGTGTTGCCAAATGGGGATGAGACCTGAGACATTGCAAGATGCAATGGCAF322109(gag)GTCTGTGTGCAAATGGGAATGCAGCCCGAGACACTGCAGGATGCGATAGC351400NC_001463(gag)TACAGTAATCATGAAAGATGGGTTACTGGAACAAGAGGAAAAGAAGGAAGAF322109(gag)AACCTTAAACATGAGAGATG........AAGTAAAAGGAAAGGAA..AAG401450NC_001463(gag)ACAAAAGAGAAAAGGAAGAGAGTGTCTTCCCAATAGTAGTGCAAGCAGCAAF322109(gag)CCATCAGAAGAAAAGAAGGGAATATATCCC..ATATTAGTGCAGGCAGGA451500NC_001463(gag)GGAGGGAGAAGCTGGAAAGCAGTAGATTCTGTAATGTTCCAGCAACTGCAAF322109(gag)GGAGGAAGAGCATGGAGAGCGGTAGAGCCTGCTACCTTTCAGCAGCTCCA501550NC_001463(gag)AACAGTAGCAATGCAGCATGGCCTCGTGTCTGAGGACTTTGAAAGGCAGTAF322109(gag)AACAGTGGCAATGCAGCATGGACTAGTATCAGAAGAATTTGAAAGGCAGC551600NC_001463(gag)TGGCATATTATGCTACTACCTGGACAAGTAAAGACATACTAGAAGTATTGAF322109(gag)TAGCATACTATGCCACCACATGGACAAGCAAGGATATCTTAGAAGTATTA601650NC_001463(gag)GCCATGATGCCTGGAAATAGAGCTCAAAAGGAGTTAATTCAAGGGAAATTAF322109(gag)GCCATGATGCCAGGAAATAGAGCGCAAAAAGAACTAATACAAGGAAAGTT651700NC_001463(gag)AAATGAAGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCTCCAGCAGAF322109(gag)AAATGAGGAAGCAGAGAGATGGAGAAGGCAGAATCCACAACCTGCGG...701750NC_001463(gag)GAGGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAAAF322109(gag)...GCGGGTTAACCGTGGATCAGATAATGGGGGTAGGACAAACGAATCAG751800NC_001463(gag)GCAGCAGCACAAGCTAACATGGATCAGGCAAGGCAAATATGCCTGCAATGAF322109(gag)GCAGCGGCACAGGCTAATATGGATCAAGCAAGACAAATATGCCTACAATG801850NC_001463(gag)GGTAATAAATGCATTAAGAGCAGTAAGACATATGGCGCACAGGCCAGGGAAF322109(gag)GGTTATAACAGCAATAAGAGGAGTTAGGCATATGGCCCATAGACCAGGAA851900NC_001463(gag)ATCCAATGCTAGTAAAGCAAAAAACGAATGAGCCATATGAAGATTTTGCAAF322109(gag)ATCCCATGCTGGTAAGACAAAAACCAAATGAGAACTATGAAGAGTTTGCC901950NC_001463(gag)GCAAGACTGCTAGAAGCAATAGATGCAGAGCCAGTTACACAGCCTATAAAAF322109(gag)GCAAGGTTGTTAGAAGCAGTGGATGCAGAACCCGTTACCCAACCTATAAA9511000NC_001463(gag)AGATTATCTAAAGCTAACACTATCTTATACAAATGCATCAGCAGATTGTCAF322109(gag)AGAATATTTAAAGGTAACTCTGTCTTACACAAATGCAAATTCGGAATGTC10011050NC_001463(gag)AGAAGCAAATGGATAGAACACTAGGACAAAGAGTACAACAAGCTAGTGTAAF322109(gag)AAAAACATATGGACAGAGTGTTGGGGCAAAGAGTACAGCAGGCCTCAATA10511100NC_001463(gag)GAAGAAAAAATGCAAGCATGTAGAGATGTGGGATCAGAAGGGTTCAAAATAF322109(gag)GAAGAAAAAATGCAGGCATGCAGGGACATCGGGGGAACAGCATATCAGAT11011150NC_001463(gag)GCAATTGTTAGCACAAGCATTAAGGCCAGGAAAAGGAAAAGGGAATGGACAF322109(gag)GCAGTTGCTTGCACAAGCCCTCCGTGGCGGAAAAGAAGATGGGAAAAAAT11511200NC_001463(gag)AGCCACAAAGGTGTTACAACTGTGGAAAACCGGGACATCAAGCAAGGCAAAF322109(gag)CTGTAGGGAAGTGTTATAACTGTGGAAGGCCCGGACACAGAGCAAAAGAA12011250NC_001463(gag)TGTAGACAAGGAATCATATGTCACAACTGTGGAAAGAGAGGACATATGCAAF322109(gag)TGCAGACAAGGCATTATATGTCACAACTGTGGAAAAAGAGGGCATATACA12511300NC_001463(gag)AAAAGAATGCAGAGGAAAGAGAGACATAAGGGGAAAACAGCAGGGAAACGAF322109(gag)GAAAAACTGCA.....AACAGAAA....AGAAGAAAGGAGCAGGGAAACA13011347NC_001463(gag)GGAGGAGGGGGATACGTGTGGTGCCGTCCGCTCCTCCTATGGAATAAAF322109(gag)TGAGGAGGGGGCTACGTGTGGTGCCGTCCGCACCCCCTATGGAGTAA表3PileUpMSF605TypeNCheck9138..NameNC_001463(5′)(SEQIDNO7)Len605Check5398Weight0NameAF322109(5′)(SEQIDNO8)Len605Check3740Weight0//150NC_001463(5′)..............GAGTTCTAGG...AGAGTCCCTCCTAGTCTCTCCTCAF322109(5′)GTGAGTGCTCTGAGGAGCTCGAAGGAAAGAGTCC.TC..AGCCTCTCCTC51100NC_001463(5′)TCCGAGGAGGTACCGAGACCTCAAATAAAGGAGTGATTGCCTTACTGCCAF322109(5′)TCCGAGGAGCTTCGG....CTCATAATAAAGGAGTGCTTGCTTCA..ACA101150NC_001463(5′)GAGTGGAGAGTGATTACTGAGCGGCCGGTGTATCGGGAGTCGTCCCTTAAAF322109(5′)GAACTGAG........CTGGTCGTGGTTATTATCGGG....GACCGAAGT151200NC_001463(5′)TCTGTGCAATACCAGAGCGGCTCTCGCAGCTGGCGCCCAACGTGGGGCCCAF322109(5′)CCCGTGCAACACCGGGGCGGTTCTCGCAGCTGGCGCCCAACGTGGGGCTC201250NC_001463(5′)GAGGAG............................................AF322109(5′)GAGTAGCTTGAGAAGCTCGACTGAGATCTGAATCCAAGAGCGACATCAGA251300NC_001463(5′)....AAGAAAAGAAAGC...GGCCCTGAGAACTCGGCTTCTG..AAAAAGAF322109(5′)CAGCAAGAAATGAGAGTAATGAGACCGCGAGCTCTGCTGCTGTAAAAAAG301350NC_001463(5′)AGGAAGAGGACAAGTTGCTATAGCAACAAGAGAGAAGAAGTAGAGCAAAGAF322109(5′)AGGAAGTAG.CGGGTTGCCGAGGCAACTGCTCAGAAGAACCAGGGGAAAG351400NC_001463(5′)GTCCAGTGGCT.CGGAAAAAGAGGAACTGAAACTTCGGGGACGCCTGAAGAF322109(5′)GGCTTCCAGCAACCTCAAAAGAGGAACCGAGACTTCGGGGACGCCTGAA.401450NC_001463(5′)GAGTAAGGTAAGTGACTCTGCTGTACGCGGGGCGAGGCAGAGGTT.TCCTAF322109(5′)..GTAAGGTAAGTGACTCTGCTGTACGCGGGGCGAGGCATAGGAGATCCT451500NC_001463(5′)TCTAAATT.GAAAGAGAAGTGTTGCTGCGAGAGGTCTTGGTGGTCGAGAAAF322109(5′)TCTATTCTAGGAAGAGAAGCGCTGTTCTGGGAGGTCTTGGCGACCGAGAA501550NC_001463(5′)TCCTGTACAAAAAAAAGGAGGGATCTCGGTCAGGACCAGGACCCCTGGGAAF322109(5′)TCTTGTT...AAATAAGCCAGGATCTCGATCAGGACCAAGACCCCTCAGG551600NC_001463(5′)GTAATACAACAGCAACACCGTAAGAAAATCCGCC................AF322109(5′)AGAGGGTATAGACAGCGTGGTAAGAAA.TCCGCCGTGGTGAGTCTAGATA601NC_001463(5′).....AF322109(5′)GAGAC表4PileUpMSF3338TypeNCheck5428..NameNC_001463(pol)(SEQIDNO9)Len3338Check8114Weight0NameAF322109(pol)(SEQIDNO10)Len3338Check7314Weight0//150NC_001463(pol)..................ATGTCACAACTGTGGAAAGAGAGGACATATGCAF322109(pol)ATGCAGACAAGGCATTATATGTCACAACTGTGGAAAAAGAGGGCATATAC51100NC_001463(pol)AAAAAGAATGCAGAGGAAAGAGAGACATAAGGGGAAAACAGCAGGGAAACAF322109(pol)AGAAAAACTGCA.....AACAGAAA....AGAAGAAAGGAGCAGGGAAAC101150NC_001463(pol)GGGAGGAGGGGGATACGTGTGGTGCCGTCCGCTCCTCCTATGGAATAACTAF322109(pol)ATGAGGAGGGGGCTACGTGTGGTGCCGTCCGCACCCCCTATGGAGTAACG151200NC_001463(pol)TCAGCACCACCTATGGTTCAGGTCCGCATAGGTTCCCAGCAGAGGAACTTAF322109(pol)CAAGCACCACTAATAGTTAGGGTACAAATAGGGAATCAGGAGAAACAATT201250NC_001463(pol)GTTATTTGATACCGGGGCGGACCGAACTATAGTTAGATGGCATGAGGGCTAF322109(pol)ATTATTTGACACAGGGGCAGATAAAACGATAGTAAGAATGCATGATGGAA251300NC_001463(pol)CGGGAAACCCAGCCGGAAGGATAAAACTGCAAGGAATAGGAGGAATAGTAAF322109(pol)CAGGGATTCCAAACGGAAGAATAAAATTACAAGGGATAGGAGGAATAGTA301350NC_001463(pol)GAAGGAGAAAAATGGAATAATGTAGAATTAGAATATAAAGGAGAAACAAGAF322109(pol)GAAGGAGAAAAATGGAATAAAGTACCCATGACATATAAGGGAGAAACATC351400NC_001463(pol)AAAGGGAACAATAGTAGTGTTACCACAAAGTCCAGTAGAAGTATTAGGACAF322109(pol)CTGCCCAAGCTTGGTTGTGCTAAGAGATAGCCCAGTAGAAGTATTGGGAA401450NC_001463(pol)GAGATAACATGGCCCGATTTGGAATAAAGATAATAATGGCAAATTTAGAGAF322109(pol)GAGATAACATGGAAGCATTCGGCGTAACCCTAATAATGGCAAATTTAGAA451500NC_001463(pol)GAAAAAAGAATCCCAATTACAAAAGTAAAATTGAAAGAGGGATGTACGGGAF322109(pol)GATAAGAAAATTCCCACAATACCAGTAGAATTGAAAGAAGGATGTAAAGG501550NC_001463(pol)TCCACATGTCCCACAATGGCCATTAACAGAAGAGAAATTAAAAGGTCTAAAF322109(pol)GCCACATGTGCCCCAGTGGCCATTAACAGCAGAGAAATTACAAGGACTAA551600NC_001463(pol)CAGAAATCATAGATAAATTAGTGGAAGAAGGAAAACTAGGAAAGGCACCCAF322109(pol)CAGGAATAGTAGAAAAATTACTACAGGAAGGAAAATTGGCAGAGGCCCCA601650NC_001463(pol)CCACATTGGACATGTAATACTCCAATCTTTTGCATAAAAAAGAAATCAGGAF322109(pol)GAGGGATGGACGTGGAACACGCCCATCTTCTGCATAAAAAAGAAGTCAGG651700NC_001463(pol)GAAGTGGAGAATGTTAATAGATTTCAGAGAATTGAACAAACAGACAGAAGAF322109(pol)AAAATGGAGAATGTTAATAGATTTTAGGGAATTAAATAAGCAAACAGCAG701750NC_001463(pol)ATTTAACAGAAGCGCAGTTAGGACTCCCGCATCCGGGAGGACTACAAAAGAF322109(pol)ATTTAGCAGAAGCGCAGCTAGGACTGCCACACCCAGGAGGGTTGCAAAGG751800NC_001463(pol)AAAAAACATGTTACAATATTGGACATAGGAGATGCATATTTTACTATACCAF322109(pol)AAAAAGAATGTAACAATTCTGGACATAGGAGATGCATATTTCACAATTCC801850NC_001463(pol)CCTATATGAACCATATCGAGAGTACACATGTTTTACTCTATTAAGTCCTAAF322109(pol)CTTATACGAGCCCTATCAGAAATATACATGCTTCACACTCCTAAGTCCTA851900NC_001463(pol)ATAATCTAGGACCATGTAAAAGATACTATTGGAAAGTGCTGCCACAAGGTAF322109(pol)ACAATTTGGGACCATGTAAAAGGTATTATTGGAAAGTATTACCCCAGGGA901950NC_001463(pol)TGGAAATTGAGTCCATCTGTATATCAATTTACTATGCAGGAGATCTTAGAAF322109(pol)TGGAAATTGAGCCCAGCTGTATATCAATTCACCATGCAAAGGTTGTTAAA9511000NC_001463(pol)GGATTGGATACAGCAGCATCCAGAAATTCAATTTGGCATATATATGGATGAF322109(pol)AGGATGGATACAACAGCATAAAAACATACAATTTGGAATATATATGGATG10011050NC_001463(pol)ATATTTACATAGGAAGTGATTTAGAAATTAAAAAGCATAGAGAAATAGTGAF322109(pol)ATATCTATATTGGAAGTGATCTAACGATAGCCCAACATAGGAAGATAATA10511100NC_001463(pol)AAAGATTTAGCCAATTATATTGCCCAATATGGATTCACTCTGCCAGAAGAAF322109(pol)GAAGAATTAGCCTCATTTATAGAACAATTTGGGTTTACATTACCAGAAGA11011150NC_001463(pol)GAAGAGACAAAAGGGATATCCAGCAAAATGGCTAGGATTTGAACTACACCAF322109(pol)TAAGAGACAAGAGGGCTATCCAGCAAAATGGCTAGGATTCGAGCTACATC11511200NC_001463(pol)CGCAGACCTGGAAATTTCAGAAGCATACATTACCTGAATTAACAAAGGGAAF322109(pol)CAGAAAAATGGAAATATCAAAAGCATAAATTGCCGGAATTACAAGAGGGG12011250NC_001463(pol)ACAATAACATTAAATAAATTACAGAAATTAGTAGGAGAATTAGTATGGAGAF322109(pol)GTAATAACCCTGAACAAATTACAGAAGATAGTAGGGGAATTAGTGTGGAG12511300NC_001463(pol)ACAATCCATAATTGGGAAAAGCATTCCTAACATTCTGAAATTAATGGAAGAF322109(pol)ACAATCCTTGATAGGAAAGAGCATCCCCAATATCATAAAATTAATGGAAG13011350NC_001463(pol)GAGATAGAGAATTACAAAGTGAAAGAAAAATTGAAGAAGTACATGTGAAAAF322109(pol)GAGATCGCGCATTACAAAGTGAAAGGAAAATAGAAAGAATACATGTACAA13511400NC_001463(pol)GAATGGGAAGCATGTAGGAAAAAATTAGAAGAAATGGAAGGAAATTATTAAF322109(pol)GAATGGGAAGCATGTCAAAAGAAATTAGATGAAATGGTAGGAAATTATTA14011450NC_001463(pol)TAATAAAGACAAAGATGTCTATGGACAATTGGCTTGGGGAGACAAAGCTAAF322109(pol)CAGAGAAGAAGAAGATATCTATGGACAAATAACTTGGGGGGATAAGGCAA14511500NC_001463(pol)TAGAATATATAGTGTATCAGGAGAAAGGGAAACCATTATGGGTAAATGTGAF322109(pol)TAAAATACATAGTATTCCAAAGGAAAGGGGAACCCCTATGGGTAAATGTA15011550NC_001463(pol)GTTCACAATATAAAGAACCTAAGCATCCCGCAACAGGTTATTAAAGCAGCAF322109(pol)GTACATGACATAAAAAATTTGAGTCTCCCACAGCAAGTGATAAAAGCAGC15511600NC_001463(pol)GCAAAAATTAACCCAAGAAGTCATCATTAGGACAGGAAAAATACCATGGAAF322109(pol)ACAGAAATTAACCCAGGAAGTAATCATAAGAACAGGAAAAATCCCATGGC16011650NC_001463(pol)TATTGTTGCCAGGGAAAGAAGAAGATTGGAGACTAGAATTGCAATTAGGGAF322109(pol)TGCTACTACCAGGAAGAGAAGAAGACTGGAGATTAGAACTGCAGGTAGGG16511700NC_001463(pol)AACATCACATGGATGCCAAAATTTTGGTCCTGTTATCGAGGA.CATACAAAF322109(pol)AACATCACGTGGATGCCATCATTTTGGTCATGTTATCGAGGAGCACCCAA17011750NC_001463(pol)GATGGAGAAAAAGAAATATAATAGAAGAAGTAGTAGAAGGGCCTACATATAF322109(pol)G.TGGAAAAGAAGGAACATAGTGGCAGCAGTGGTAGATGGACCGACATAT17511800NC_001463(pol)TATACAGATGGAGGAAAAAAGAATAAAGTAGGAAGTCTAGGGTTCATAGTAF322109(pol)TATACAGATGGGGGAAAGAAAAACGCACAGGGAAGCTTTGGCTTCATCTC18011850NC_001463(pol)ATCAACAGGGGAAAAATTTAGAAAGCATGAAGAGGGCACAAACCAGCAACAF322109(pol)CCCAACAGGAGAAAAGTTCAGAAGGCATGAAGATGGAACTAATCAGGTAT18511900NC_001463(pol)TAGAATTAAGAGCCATAGAGGAAGCTCTAAAACAAGGGCCTCAAACAATGAF322109(pol)TAGAATTAAGGGCAATAGAAGATCCATGTAAACAAGGACCTGAAAGCATG19011950NC_001463(pol)AATTTAGTAACAGATAGTAGATATGCATTTGAATTTTTATTAAGAAATTGAF322109(pol)AACATTGTAACTGACAGCAGGTATGCTTATGAATTCATGCTCCGAAACTG19512000NC_001463(pol)GGATGAAGAAGTAATAAAGAATCCAATTCAAGCAAGAATTATGGAAATTGAF322109(pol)GGATGAACAGGTCATAAGAAACCCCATTCAGGCAAGAATCATGGCAGAAG20012050NC_001463(pol)CCCACAAGAAAGATAGGATAGGAGTGCATTGGGTGCCAGGACATAAAGGGAF322109(pol)TGCACAAGAAAAAGCAGGTAGGAATACACTGGGTGCCAGGGCATAAAGGA20512100NC_001463(pol)ATTCCCCAAAATGAAGAAATAGACAAATATATTTCGGAAATATTTCTTGCAF322109(pol)ATACCTCAGAATGAAGAGATAGACCAGTACATATCAGAAGTATTCTTAGC21012150NC_001463(pol)AAAAGAAGGAGAAGGAATTCTCCCAAAAAGAGAAGAGGATGCAGGGTATGAF322109(pol)AGGAGAAGGAACAGGGATATGTGAAAAAAGGAAGGAAGATGCTGGATATG21512200NC_001463(pol)ATTTAATATGCCCAGAAGAGGTTACCATAGAGCCAGGACAAGTGAAATGCAF322109(pol)ATTTATTATGCCCGCATGAGGTAATACTTAAACCCCAAGAAGTAAAACGG22012250NC_001463(pol)ATCCCCATAGAGCTAAGATTAAATTTAAAGAAATCACAATGGGCTATGATAF322109(pol)ATCCCAATAGACCTAAAATTAAAATTGAAAGAAAAGCAATGGGCCATGAT22512300NC_001463(pol)TGCTACAAAAAGCAGCATGGCTGCCAAAGGAGTGTTCACACAAGGAGGAAAF322109(pol)AAGTGGGAAAAGTAGCGTTGCAGCAAAAGGAATATTTGTACAAGGAGGCA23012350NC_001463(pol)TCATAGACTCAGGATATCAGGGACAAATACAGGTAATAATGTATAATAGCAF322109(pol)TAATAGATTCAGGGTATCAGGGACAAGTACAAGTCATCCTATATAATAGT23512400NC_001463(pol)AATAAAATAGCAGTAGTCATACCCCAAGGGAGAAAATTTGCACAATTAATAF322109(pol)AATAAGATAGAGGTCAAAATACCACAAGGCAGGAAATTTGCCCAATTAAT24012450NC_001463(pol)ATTAATGGATAAAAAGCATGGAAAATTGGAACCCTGGGGGGAAAGCAGAAAF322109(pol)ATTAATGAACTTACAACATGAAGAATTAGAAGAATGGGGAAAGGAAAGAA24512500NC_001463(pol)AAACAGAAAGGGGAGAAAAAGGATTTGGGTCTACAGGAATGTATTGGATAAF322109(pol)AAACAGAAAGAGGAACAAAAGGATTTGGGTCTACAGGAGCATTTTGGATA25012550NC_001463(pol)GAAAATATTCCTCTGGCAGAGGAAGACCACACAAAATGGCATCAAGATGCAF322109(pol)GAGAATATTCCCCAAGCAGAGGAAGAACATTACAAATGGCATCAAGATGC25512600NC_001463(pol)CCGATCATTGCATCTAGAATTTGAAATTCCAAGAACAGCAGCAGAAGACAAF322109(pol)TAGATCTCTGCAGCTAGAATTCAAGATACCTAGAGCAGCAGCAGAAGACA26012650NC_001463(pol)TAGTAAATCAATGTGAAATATGCAAAGAAGCGAGGACACCTGCAGTAATTAF322109(pol)TTATACAGCACTGTGAGGTATGTCAAGAAGGCAAACCCGCAGCGATCACG26512700NC_001463(pol)AGAGGCGGAAACAAAAGGGGGGTAAATCATTGGCAAGTGGATTATACCCAAF322109(pol)AGAGGGGGAAATAAAAGAGGAATAGATCATTGGCAGGTAGACTATACACA27012750NC_001463(pol)TTATGAAAATATCATACTATTAGTATGGGTAGAAACAAATTCAGGACTAAAF322109(pol)TTACAAAGAACACATAATATTAGTATGGGTAGAGACTAATTCAGGATTAA27512800NC_001463(pol)TATATGCAGAAAAAGTAAAAGGAGAATCAGGGCAAGAATTCAGAATAAAAAF322109(pol)TATTTGCAGAGAAAGTAAAAGGAGAATCAGGACAAGAATTTAGGATGCAG28012850NC_001463(pol)GTGATGCATTGGTATGCATTATTTGGTCCAGAGTCATTGCAGTCAGACAAAF322109(pol)ACATTGAAATGGTATGCTTTGTTTCAACCAAAATCAGTGCAATCAGATAA28512900NC_001463(pol)TGGACCTGCATTTGCAGCAGAGCCCACACAGCTGTTAATGCAATACCTAGAF322109(pol)TGGGACAGCCTTCACAGCTGAGGCTACGCAGCATCTAATGAAGTATTTAG29012950NC_001463(pol)GAGTAAAACACACAACAGGCATACCTTGGAATCCACAGTCTCAGGCTATAAF322109(pol)GGATTCAGCACACTACGGGTATTCCGTGGAACCCCCAGTCACAAAGTTTA29513000NC_001463(pol)GTAGAAAGGGCACATCAACTATTGAAAAGCACTTTAAAGAAGTTCCAGCCAF322109(pol)GTAGAAAGAGCTCATCAAACATTAAAACACATGTTAGAAAAATTAGAACC30013050NC_001463(pol)ACAATTTGTCGCTGTAGAATCAGCCATAGCAGCAGCCCTAGTCGCCATAAAF322109(pol)ACAATTTGTGGCCCTACAGTCTGCCATCGCAGCCACTCTAGTTGCGCTCA30513100NC_001463(pol)ATATAAAAAGAAAGGGTGGGCTGGGGACAAGCCCTATGGATATTTTTATAAF322109(pol)ATATAAAAAGAAAGGGTGGACTAGGGGCAAGCCCTATGGATATTTACATA31013150NC_001463(pol)TATAATAAAGAACAGAAAAGAATAAATAATAAATATAATAAAAATTCTCAAF322109(pol)TATAATAAGGAGCAACAAAGACAACAAGATAATAGTAATAAATTAATTCA31513200NC_001463(pol)AAAAATTCAATTCTGTTATTACAGAATAAGGAAAAGAGGACATC.AGGAGAF322109(pol)GAAAA...AATTTTGTTATTACAGGATCAGAAAAAGAGGCCATCCAGGAG32013250NC_001463(pol)AGTGGAAAGGACCAACCCAGGTACTGTGGAAAGGGGAAGGAGCCAATTGTAF322109(pol)AGTGGAACGGCCCAACTGAGGTACTGTGGGAAGGGGAAGGAGCCA.TAGT32513300NC_001463(pol)GGTAAAGGATATAGAAAGTGAAAAGTATTTAGTAATACCTTACAAAGATGAF322109(pol)AGTTAAAGACAAAGAAAGTGATAGATATCTAGTCATCCCATATAAAGATG33013338NC_001463(pol)CAAAATTCATCCCGCCACCAACAAAAGAAAAGGAATAAAF322109(pol)CAAAATTTATTCCGCCACCGTCGGAACAGAAGGGATAG表5PileUpMSF408TypeNCheck517..NameNC_001463(rev)(SEQIDNO11)Len408Check7287Weight0NameAF322109(rev)(SEQIDNO12)Len408Check3230Weight0//150NC_001463(rev)ATGGATGCTGGGGCCAGATACATGCGCTTAACTGGGAAGGAAAACTGGGTAF322109(rev)..................................................51100NC_001463(rev)TGAAGTAACCATGGACGGAGAGAAGGAAAGGAAAAGAGAAGGTTTCACTGAF322109(rev)..........ATGG.CGGAGATAAGAAAAG..A.AGCAAAGGAGCCACTA101150NC_001463(rev)CGGGACAGCAAGATATACAGAACTCTAAGTACCCCGACATACCAACGGGTAF322109(rev)ATCCAGGACCAGGTATCAACAAGTCAACTTGGTGATGGAGACC..CGGGT151200NC_001463(rev)CACAGTCATCATGGAAACAAGAGCAGACGTCGCAGGAGAAAATCAGGATTAF322109(rev)............GCAACTAGAAGAAGAAGAAGAAGAAGACGGAAGGGATG201250NC_001463(rev)TTGGCGATGGCTTAGAGGAATCAGACAACAGCGAAACAAGCGAAAGAGTGAF322109(rev)GTGGAGATGGCTCAGAGAGATG......CAGCGATCCCGACAACAAAGGA251300NC_001463(rev)ACAGTACAGAAAGCTTGGAGCCGTGCCTGGGAGCTTTGGCAGAACTCACCAF322109(rev)A...TTATGAACGCCTGGAGGAGAGCTTGGGTGACTTGGAGAAACTCACC301350NC_001463(rev)CTGGAAGGAGCCATGGAAAAGGGGCCTGCTGAGGCTGCTCGTCCTTCCGCAF322109(rev)TTGGCAGAACACATGGAAGAATGTGGTGGTGGCGCCGTTGGTGATTCCGC351400NC_001463(rev)TGACGATGGGAATCTGGATAAATGGATGGCTTGGAGAACACCACAAAAATAF322109(rev)TGACAATCAGAATTTGGCTCCTTGGAGAGAATGGAGAGAACCCCTAAAAG401NC_001463(rev)AA......AF322109(rev)AAAAATAA表6PileUpMSF691TypeNCheck6528..NameNC_001463(vif)(SEQIDNO13)Len691Check5882Weight0NameAF322109(vif)(SEQIDNO14)Len691Check646Weight0//150NC_001463(vif)ATGCAAAATTCATCCCGCCACCAACAAAAGAAAAGGAATAAAAAACCTGGAF322109(vif)ATGCAAAATTTATTCCGCCACCGTCGGAACAGAAGGGATAGAAGAATAGG51100NC_001463(vif)ACCAGAATTACCCTTAGCACTATGGATACATATAGCAGAAAGCATTAATGAF322109(vif)TCCAGAATTGCCTTTATCTTTATGGACTTATACAGCATACAGCATAAATA101150NC_001463(vif)GGGATAGCTCATGGTACATAACAATGAGACTGCAACAGATGATGTGGGGAAF322109(vif)AAGATCCCGCATGGTATACAACCCTAAGACTGCAGCAAATGATGTGGCAT151200NC_001463(vif)AAAAGAGGAAATAAGTTACAATATAAGAATGAAGACAGGGAATATGAAAAAF322109(vif)AGGAGGGGAAATAAATTGACATATGTCAGGGAAAATGCACAGTACGAGGA201250NC_001463(vif)TTGGGAAATTACATCATGGGGATGGAAAATGCACCTAAGGAGAGTGAAACAF322109(vif)GTGGGAAATGACCTCGTATGAGTGGAGGATAAGAATGAGAAGGGACAAAA251300NC_001463(vif)AATGGATACAAGACAACAGGAGAGGAAGC.CCATGGCAGTACAAAGTAGGAF322109(vif)CAAAAAGTCATC.CAAGAGGGCATACTTCGCCATGGCAATATCGGAGACA301350NC_001463(vif)AGGAACATGGAAAAGTATAGGAGTGTGGTTCCTGCAAGCAGGAGATTACAAF322109(vif)GGATGGATGGAAGGATGTGGGAACGTGGTTCCTACAGCCAGGGGACTATA351400NC_001463(vif)GAAAGGTAGACAGGCACTTCTGGTGGGCATGGAGGATACTGATATGTTCCAF322109(vif)GAAAGGCGGATCAGCAGTTCTGGTTCGCTTGGAGAATAGTGTCGTGTTCA401450NC_001463(vif)TGCAGGAAAGAAAAGTTTGATATAAGAGAATTTATGAGAGGAAGACATAGAF322109(vif)TGTAAAAAGGAAGGATTTAACATAAGAGAATTTATGCTAGGTACCCATAG451500NC_001463(vif)ATGGGATTTGTGCAAATCCTGTGCTCAAGGAGAAGTAGTAAAGCATACTAAF322109(vif)ATGGGATTTGTGTAAGTCGTGTTGCCAGGGTGAAGTAGTAAAGAGAACAC501550NC_001463(vif)GAACAAAAAGTCTGGAAAGACTAGTACTGCTACAGATGGTAGAACAGCATAF322109(vif)AACCCTACACCTTGCAAAGGCTCACGTGGCTTAAATTAACAGAAGACCAT551600NC_001463(vif)GTGTTTCAAGTATTGCCATTGTGGAGAGCCAGGAGAAGTAGTACAACAGAAF322109(vif)GTATTTCAAGTAATGCCCTTGTGGAGAGCTCGCAAAGGGATTACCATAGA601650NC_001463(vif)TTTCCCATGGTGCAGGGACACAACGGGATACACGCATGCGTGGTCTGTCCAF322109(vif)CTTTCCCTGGTGCAGGGACACAAAAGGATTCCTGGAGCCGTGGACAACGC651691NC_001463(vif)AGGAGTGCTGGTTGATGGAATATCTCTTAGAGGATGAGTGAAF322109(vif)AAGAGTGTTGGCAAATAGAGTATCCCTTGGAGGATGAGTGA表7PileUpMSF736TypeNCheck513..NameNC_001463(gag720bp)(SEQIDNO15)Len736Check4701Weight0Name>AF015181(SEQIDNO16)Len736Check5812Weight0//150NC_001463(gag720bp).ATGGTGAGTCTAGATAGAGACATGGCGAGGCAAGTCTCCGGGGGGAAAA>AF015181GCTGTAGACTCTGTAATGTTCCAACAA.ATGCAAA....CAGTAGCAATG51100NC_001463(gag720bp)GAGATTATCCTGAGCTCGAAAAATGTATCAAGCATGCATGCAAGATAAAA>AF015181CAGCATGGCCTCGTGTCCGAGGATTTTGAAAGACAGTTAGCAT.ATTATG101150NC_001463(gag720bp)GTTCGACTCAGAGGGG..AGCACTTGACAGAAGGAAATTGTTTATGGTGC>AF015181CTACTACCTGGACAAGTAAAGACATACTAGAAGTA..TTGGCCATGATGC151200NC_001463(gag720bp)CTTAAAACA....TTAGATT..ACATGTTTGAGGACCAT..AAAGAGGAA>AF015181CTGGGAATAGGGCTCAGAAAGAACTTATTCAAGGGAAATTGAATGAAGAA201250NC_001463(gag720bp)CCTTGGACAAAAGTAAAATTTAGGACAATATGGCAGAAGG.TGAAGAATC>AF015181GCA..GACAGGTGGAGAAG...GAACAATCCACCAGGAGGATTAACAGTG251300NC_001463(gag720bp)TAACTCCTGAGGAGAGTAACAAAAAAGACTTTATGTCTTTGCAGGCCACA>AF015181GATCAAATTATGGGGGTAGGACAAACAAATCAAGCA....GCAGCACAAG301350NC_001463(gag720bp)TTAGCGGGTCTAATGTGTTGCCAAATGGGGATGAGACCTGAGACATTGCA>AF015181CTAACATGGATCAGGCAA.GACAAATATGCCT...ACAATGGGTAATAAA351400NC_001463(gag720bp)AGATGCAATGGCTACAGTAATCATGAAAGATGGGTTACTGGAACAAGAGG>AF015181CGCCTTAAGAGCAGTAAGGCATATGGCTCATAGGCCAGGGAATCCAATGC401450NC_001463(gag720bp)AAAAGAAGGAAGACAAAAGAGAAAAGGAAGAGAGTGTCTTCCCAATAGTA>AF015181TAGTAAAGCAA...AAAACAAATGAGCCATATGAAGAATTTGCAGCAAGA451500NC_001463(gag720bp)GTGCAAGCAGCA..GGAGGGAGAAGCTGGAAAGCAGTAGATTCTGTAATG>AF015181CTGCTAGAAGCAATAGATGCAGAAGCGGTTACACAGCCCATAAAAGAGTA501550NC_001463(gag720bp)T.TCCAGC.AACTGCAAACAGTAGCAATGCAGCATGGCCTCGTGTCTGAG>AF015181TCTAAAGCTAACATTATCCTATACAAATGCAGC.....CTCA........551600NC_001463(gag720bp)GACTTTGAAAGGCAGTTGGCATATTATGCTACTACCTGGACAAGTAAAGA>AF015181GATTGTCAAAAGCAAATGG.AGAGAGTGCTAGGACAAAGA...GTACA.A601650NC_001463(gag720bp)CATACTAGAAGTATTGGCCATGATGCCTGGAAATAGAGCTCAAAAGGAGT>AF015181CAGGCTAGT.GTAGAAAAAAAAATGCAAGCATGT................651700NC_001463(gag720bp)TAATTCAAGGGAAATTAAATGAAGAAGCAGAAAGGTGGAGAAGGAATAAT>AF015181..................................................701736NC_001463(gag720bp)CCACCACCTCCAGCAGGAGGAGGATTAACAGTGGAT>AF015181....................................PileUpMSF1347TypeNCheck939..NameNC_001463(gag)(SEQIDNO17)Len1347Check6959Weight0Name>AF015181(SEQIDNO18)Len1347Check3980Weight0//150NC_001463(gag)ATGGTGAGTCTAGATAGAGACATGGCGAGGCAAGTCTCCGGGGGGAAAAG>AF015181..................................................51100NC_001463(gag)AGATTATCCTGAGCTCGAAAAATGTATCAAGCATGCATGCAAGATAAAAG>AF015181..................................................101150NC_001463(gag)TTCGACTCAGAGGGGAGCACTTGACAGAAGGAAATTGTTTATGGTGCCTT>AF015181..................................................151200NC_001463(gag)AAAACATTAGATTACATGTTTGAGGACCATAAAGAGGAACCTTGGACAAA>AF015181..................................................201250NC_001463(gag)AGTAAAATTTAGGACAATATGGCAGAAGGTGAAGAATCTAACTCCTGAGG>AF015181..................................................251300NC_001463(gag)AGAGTAACAAAAAAGACTTTATGTCTTTGCAGGCCACATTAGCGGGTCTA>AF015181..................................................301350NC_001463(gag)ATGTGTTGCCAAATGGGGATGAGACCTGAGACATTGCAAGATGCAATGGC>AF015181..................................................351400NC_001463(gag)TACAGTAATCATGAAAGATGGGTTACTGGAACAAGAGGAAAAGAAGGAAG>AF015181..................................................401450NC_001463(gag)ACAAAAGAGAAAAGGAAGAGAGTGTCTTCCCAATAGTAGTGCAAGCAGCA>AF015181..................................................451500NC_001463(gag)GGAGGGAGAAGCTGGAAAGCAGTAGATTCTGTAATGTTCCAGCAACTGCA>AF015181..................GCTGTAGACTCTGTAATGTTCCAACAAATGCA501550NC_001463(gag)AACAGTAGCAATGCAGCATGGCCTCGTGTCTGAGGACTTTGAAAGGCAGT>AF015181AACAGTAGCAATGCAGCATGGCCTCGTGTCCGAGGATTTTGAAAGACAGT551600NC_001463(gag)TGGCATATTATGCTACTACCTGGACAAGTAAAGACATACTAGAAGTATTG>AF015181TAGCATATTATGCTACTACCTGGACAAGTAAAGACATACTAGAAGTATTG601650NC_001463(gag)GCCATGATGCCTGGAAATAGAGCTCAAAAGGAGTTAATTCAAGGGAAATT>AF015181GCCATGATGCCTGGGAATAGGGCTCAGAAAGAACTTATTCAAGGGAAATT651700NC_001463(gag)AAATGAAGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCTCCAGCAG>AF015181GAATGAAGAAGCAGACAGGTGGAGAAGGAACAATCCACCA..........701750NC_001463(gag)GAGGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAA>AF015181..GGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAA751800NC_001463(gag)GCAGCAGCACAAGCTAACATGGATCAGGCAAGGCAAATATGCCTGCAATG>AF015181GCAGCAGCACAAGCTAACATGGATCAGGCAAGACAAATATGCCTACAATG801850NC_001463(gag)GGTAATAAATGCATTAAGAGCAGTAAGACATATGGCGCACAGGCCAGGGA>AF015181GGTAATAAACGCCTTAAGAGCAGTAAGGCATATGGCTCATAGGCCAGGGA851900NC_001463(gag)ATCCAATGCTAGTAAAGCAAAAAACGAATGAGCCATATGAAGATTTTGCA>AF015181ATCCAATGCTAGTAAAGCAAAAAACAAATGAGCCATATGAAGAATTTGCA901950NC_001463(gag)GCAAGACTGCTAGAAGCAATAGATGCAGAGCCAGTTACACAGCCTATAAA>AF015181GCAAGACTGCTAGAAGCAATAGATGCAGAAGCGGTTACACAGCCCATAAA9511000NC_001463(gag)AGATTATCTAAAGCTAACACTATCTTATACAAATGCATCAGCAGATTGTC>AF015181AGAGTATCTAAAGCTAACATTATCCTATACAAATGCAGCCTCAGATTGTC10011050NC_001463(gag)AGAAGCAAATGGATAGAACACTAGGACAAAGAGTACAACAAGCTAGTGTA>AF015181AAAAGCAAATGGAGAGAGTGCTAGGACAAAGAGTACAACAGGCTAGTGTA10511100NC_001463(gag)GAAGAAAAAATGCAAGCATGTAGAGATGTGGGATCAGAAGGGTTCAAAAT>AF015181GAAAAAAAAATGCAAGCATGT.............................11011150NC_001463(gag)GCAATTGTTAGCACAAGCATTAAGGCCAGGAAAAGGAAAAGGGAATGGAC>AF015181..................................................11511200NC_001463(gag)AGCCACAAAGGTGTTACAACTGTGGAAAACCGGGACATCAAGCAAGGCAA>AF015181..................................................12011250NC_001463(gag)TGTAGACAAGGAATCATATGTCACAACTGTGGAAAGAGAGGACATATGCA>AF015181..................................................12511300NC_001463(gag)AAAAGAATGCAGAGGAAAGAGAGACATAAGGGGAAAACAGCAGGGAAACG>AF015181..................................................13011347NC_001463(gag)GGAGGAGGGGGATACGTGTGGTGCCGTCCGCTCCTCCTATGGAATAA>AF015181...............................................表8PileUpMSF727TypeNCheck1231..NameNC_001463(gag720bp)(SEQIDNO19)Len727Check1714Weight0Name>AF402664(SEQIDNO20)Len727Check1659Weight0Name>AF402665(SEQIDNO21)Len727Check331Weight0Name>AF402666(SEQIDNO22)Len727Check7190Weight0Name>AF402667(SEQIDNO23)Len727Check9833Weight0Name>AF402668(SEQIDNO24)Len727Check504Weight0//150NC_001463(gag720bp)ATGGTGAGTCTAGATAGAGACATGGCGAGGCAAGTCTCCGGGGGGAAAAG>AF402664........TCAAGCAGCAGG.AGGGAGAAGCTGGAAAGCAGTAGACTCAG>AF402665........GCAAGCAGCAGG.AGGGAGAAGCTGGAAAGCAGTAGACTCAG>AF402666........GCAAGCAGCAGG.AGGGAGAAGCTGGAAAGCAGTAGACTCAG>AF402667........GCAAGCAGCAGG.AGGGAGAAGCTGGAAAGCAGTAGACTCAG>AF402668........GCAAGCAGCAGG.AGGGAGAAGCTGGAAAGCAGTAGACTCAG51100NC_001463(gag720bp)AGATTATCCTGAGCTCGAAAAATGTATCAAGCATGCATGCAAGATAAAAG>AF402664TGATGTTCCAGCAACTGCAAAATGTAGCAATGCAGCATGGCCTCGTGTCC>AF402665TGATGTTCCAGCAACTGCAAAATGTAGCAATGCAGCATGGCCTCGTGTCC>AF402666TGATGTTCCAGCAACTGCAAAATGTAGCAATGCAGCATGGCCTCGTGTCC>AF402667TGATGTTCCAGCAACTGCAAAATGTAGCAATGCAGCATGGCCTCGTGTCC>AF402668TGATGTTCCAGCAACTGCAAAATGTAGCAATGCAGCATGGCCTCGTGTCC101150NC_001463(gag720bp)TTCGACTCAGAGGGGAGCACTTGACAGAAGGAAATTGTTTATGGTGCCTT>AF402664GAGGATTTTGAAAGG..CAGTTAGTATATTATGCTACTACCTGGACAAGT>AF402665GAGGATTTTGAAAGG..CAGTTAGCATATTATGCTACTACCTGGACAAGT>AF402666GAGGATTTTGAAAGG..CAGTTGGCATATTATGCTACTACCTGGACAAGT>AF402667GAGGATTTTGAAAGG..CAGTTAGCATATTATGCTACTACCTGGACAAGT>AF402668GAGGATTTTGAAAGG..CAGTTAGCATATTATGCTACTACCTGGACAAGT151200NC_001463(gag720bp)AAAACATTAGATTACATGTTTGAGGACCATAAAGAGGAACCTTGGACAAA>AF402664AAAGA..TATATTAGAAGTATTGG..CCATGATG.....CCTGGAAATAG>AF402665AAAGA..TATATTAGAAGTATTGG..CCATGATG.....CCTGGAAATAG>AF402666AAAGA..TATATTAGAAGTATTGG..CCATGATG.....CCTGGAAACAG>AF402667AAAGA..TATATTAGAAGTATTGG..CCATGATG.....CCTGGAAATAG>AF402668AAAGA..TATATTAGAAGTATTGG..CCATGATG.....CCTGGAAATAG201250NC_001463(gag720bp)AGTAAAATTTAGGACAATATGGCAGAAGGTGAAGAATCTAACTCCTGAGG>AF402664AGCTCAAAAAGAGTTAATTCAAGGGAAATTGAATGAGGAAGCAGAAAGGT>AF402665AGCTCAAAAAGAGTTAATTCAAGGGAAATTGAATGAGGAAGCAGAAAGGT>AF402666AGCTCAAAAAGAGTTAATTCAGGGGAAATTGAATAAGGAAGCAGAAAGGT>AF402667AGCTCAAAAAGAGTTAATTCAAGGGAAATTGAATGAGGAAGCAGAAAGGT>AF402668AGCTCAAAAAGAGTTAATTCAAGGGAAATTGAATGAGGAAGCAGAAAGGT251300NC_001463(gag720bp)AGAGTAACAAAAAAGACTTTATGTCTTTGCAGGCCACATTAGCGGGTCTA>AF402664GGAG.AAGAAATAATCCACCACCTCAA.GCAGGCG......GAGGATTAA>AF402665GGAG.AAGGAATAATCCACCACCTCAA.GCAGGCG......GAGGATTAA>AF402666GGAG.AAGGAATAATCCACCACCTCAA.GCACAAG......GAGGATTAA>AF402667GGAG.AAGGAATAATCCACCACCTCAA.GCAGGCG......GAGGATTAA>AF402668GGAG.AAGGAATAATCCACCACCTCAA.GCAGGCG......GAGGATTAA301350NC_001463(gag720bp)ATGTGTTGCCAA..ATGGGGATGAGACCTGAGACATTGCAAGATGCAATG>AF402664CAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAAGCAGCGGCACAG>AF402665CAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAAGCAGCGGCACAG>AF402666CAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAGGCAGCGGCACAG>AF402667CAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAAGCAGCGGCACAG>AF402668CAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAAGCAGCGGCACAG351400NC_001463(gag720bp)GCTA.CAGTAATCATGAAAGATGGGTT..ACTGGAACAAG.AGGAAAAGA>AF402664GCTAACATGGATCAGGCAAGACAAATATGTCTGCAATGGGTAATAACAGC>AF402665GCTAACATGGATCAGGCAAGACAAATATGCCTGCAATGGGTAATAACAGC>AF402666GCTAACATGGATCAGGCAAGACAAATATGCCTGCAATGGGTAATAACAGC>AF402667GCTAACATGGATCAGGCAAGACAAATATGCCTGCAATGGGTAATAACAGC>AF402668GCTAACATGGATCAGGCAAGACAAATATGCCTGCAATGGGTAATAACAGC401450NC_001463(gag720bp)AGGAAGACAAAAGAGAAAAGGAAGAGAGTGTCTTCCCAATAGTAGTGCAA>AF402664ACTAAGAGCAGTGAGACATATGGCTCACAAACCAGGGAATCCAA.TGCTA>AF402665ACTAAGAGCAGTGAGACATATGGCTCACAAACCAGGGAATCCAA.TGCTA>AF402666ACTAAGAGCAGTGAGACATATGGCTCACAAACCAGGGAATCCAA.TGCTA>AF402667ACTAAGAGCAGTGAGACATATGGCTCACAAACCAGGGAATCCAA.TGCTA>AF402668ACTAAGAGCAGTGAGACATATGGCTCACAAACCAGGGAATCCAA.TGCTA451500NC_001463(gag720bp)GCAGCAGGAGGGAGAAGCTGGAAAGCAGTAGATTCTGTAATGTTCCAGCA>AF402664GTAAAGCAAAAAACAAATGAGTCATATGAAGATTTTGCCGCAAGACTGCT>AF402665GTAAAGCAAAAGACAAATGAGTCATATGAAGATTTTGCCGCAAGACTGCT>AF402666GTAAAGCAAAAGACAAATGAGTCATATGAAGATTTTGCCGCAAGACTGCT>AF402667GTAAAGCAAAAGACAAATGAGTCATATGAAGATTTTGCCGCAAGACTGCT>AF402668GTAAAGCAAAAGACAAATGAGTCATATGAAAAATTTTCAGCAAGACTCCT501550NC_001463(gag720bp)ACTGCAAACAGTAGCA.ATGCAGCATGGCCTCGTGTCTGAGGACTTTGAA>AF402664AGAAGCAATAGATGCAGAACCAGTTACACAGCAAATAAAAGAATATTTAA>AF402665AGAAGCAATAGATGCAGAACCAGTTACACAGCAAATAAAAGAATATTTAA>AF402666AGAAGCAATAGATGCAGAACCAGTTACACAGCAAATAAAAGAATATTTAA>AF402667AGAAGCAATAGATGCAGAACCAGTTACACAGCAAATAAA.GAATATTTAA>AF402668AGAAGCAATAGATGCAGAACCAGTTACACAGCCTATAAAAGAATATTTAA551600NC_001463(gag720bp)AGGCAGTTGGCATATTATGCTACTACCTGGACAAGTAAAGACATACTAGA>AF402664AGTTA......ACATTATCTTAC.ACAAATGCATCCTCAGACTGTCAGAA>AF402665AGTTA......ACATTATCTTAC.ACAAATGCATCCTCAGACTGTCAAAA>AF402666AGTTA......ACATTATCTTAC.ACAAATGCATCCTCAGACTGTCAGAA>AF402667..................................................>AF402668AGTTA......ACATTATCTTAC.ACAAATGCATCCTCAGACTGTCAAAA601650NC_001463(gag720bp)AGTATTGGCCATGATGCCTGGAAATAGAGCTCAAAAGGAGTTAATTCAAG>AF402664ACAGATGGATAGAGTACTAGGACAGAGAGTGCAACAAGCTAGTGTGGAAG>AF402665ACAAATGGATAGAATACTAGGACAGAGAGTGCAACAAGCTAGTGTGGAAG>AF402666ACAAATGGATAGAGTACTAGGACAGAGAGTGCAACAAGCTAGTGTGGAAG>AF402667..................................................>AF402668ACAAATGGATAGAGTACTAGGACAGAGAGTGCAACAAGCTAGTGTGGAAG651700NC_001463(gag720bp)GGAAATTAAATGAAGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCT>AF402664AAAAAATGCAAGCAT..GCAGAGATGTGGGATCAGAAGGATTCAGAATGC>AF402665AAAAAATGCAAGCAT..GCAGAGATGTGGGATCAGAAGGGTTCAGAATGC>AF402666AAAAAATGCAAGCAT..GCAGAGATGTGGGATCAGAAGG...........>AF402667..................................................>AF402668AAAAAATGCAAGCAT..GCAGAGATGTGGGATCAGAAGGATTCAGAATGC701727NC_001463(gag720bp)CCAGCAGGAGGAGGATTAACAGTGGAT>AF402664...........................>AF402665...........................>AF402666...........................>AF402667...........................>AF402668...........................PileUpMSF1347TypeNCheck5320..NameNC_001463(gag)(SEQIDNO25)Len1347Check6959Weight0Name>AF402664(SEQIDNO26)Len1347Check1590Weight0Name>AF402665(SEQIDNO27)Len1347Check9222Weight0Name>AF402666(SEQIDNO28)Len1347Check4950Weight0Name>AF402667(SEQIDNO29)Len1347Check3156Weight0Name>AF402668(SEQIDNO30)Len1347Check9443Weight0//150NC_001463(gag)ATGGTGAGTCTAGATAGAGACATGGCGAGGCAAGTCTCCGGGGGGAAAAG>AF402664..................................................>AF402665..................................................>AF402666..................................................>AF402667..................................................>AF402668..................................................51100NC_001463(gag)AGATTATCCTGAGCTCGAAAAATGTATCAAGCATGCATGCAAGATAAAAG>AF402664..................................................>AF402665..................................................>AF402666..................................................>AF402667..................................................>AF402668..................................................101150NC_001463(gag)TTCGACTCAGAGGGGAGCACTTGACAGAAGGAAATTGTTTATGGTGCCTT>AF402664..................................................>AF402665..................................................>AF402666..................................................>AF402667..................................................>AF402668..................................................151200NC_001463(gag)AAAACATTAGATTACATGTTTGAGGACCATAAAGAGGAACCTTGGACAAA>AF402664..................................................>AF402665..................................................>AF402666..................................................>AF402667..................................................>AF402668..................................................201250NC_001463(gag)AGTAAAATTTAGGACAATATGGCAGAAGGTGAAGAATCTAACTCCTGAGG>AF402664..................................................>AF402665..................................................>AF402666..................................................>AF402667..................................................>AF402668..................................................251300NC_001463(gag)AGAGTAACAAAAAAGACTTTATGTCTTTGCAGGCCACATTAGCGGGTCTA>AF402664..................................................>AF402665..................................................>AF402666..................................................>AF402667..................................................>AF402668..................................................301350NC_001463(gag)ATGTGTTGCCAAATGGGGATGAGACCTGAGACATTGCAAGATGCAATGGC>AF402664..................................................>AF402665..................................................>AF402666..................................................>AF402667..................................................>AF402668..................................................351400NC_001463(gag)TACAGTAATCATGAAAGATGGGTTACTGGAACAAGAGGAAAAGAAGGAAG>AF402664..................................................>AF402665..................................................>AF402666..................................................>AF402667..................................................>AF402668..................................................401450NC_001463(gag)ACAAAAGAGAAAAGGAAGAGAGTGTCTTCCCAATAGTAGTGCAAGCAGCA>AF402664........................................TCAAGCAGCA>AF402665........................................GCAAGCAGCA>AF402666........................................GCAAGCAGCA>AF402667........................................GCAAGCAGCA>AF402668........................................GCAAGCAGCA451500NC_001463(gag)GGAGGGAGAAGCTGGAAAGCAGTAGATTCTGTAATGTTCCAGCAACTGCA>AF402664GGAGGGAGAAGCTGGAAAGCAGTAGACTCAGTGATGTTCCAGCAACTGCA>AF402665GGAGGGAGAAGCTGGAAAGCAGTAGACTCAGTGATGTTCCAGCAACTGCA>AF402666GGAGGGAGAAGCTGGAAAGCAGTAGACTCAGTGATGTTCCAGCAACTGCA>AF402667GGAGGGAGAAGCTGGAAAGCAGTAGACTCAGTGATGTTCCAGCAACTGCA>AF402668GGAGGGAGAAGCTGGAAAGCAGTAGACTCAGTGATGTTCCAGCAACTGCA501550NC_001463(gag)AACAGTAGCAATGCAGCATGGCCTCGTGTCTGAGGACTTTGAAAGGCAGT>AF402664AAATGTAGCAATGCAGCATGGCCTCGTGTCCGAGGATTTTGAAAGGCAGT>AF402665AAATGTAGCAATGCAGCATGGCCTCGTGTCCGAGGATTTTGAAAGGCAGT>AF402666AAATGTAGCAATGCAGCATGGCCTCGTGTCCGAGGATTTTGAAAGGCAGT>AF402667AAATGTAGCAATGCAGCATGGCCTCGTGTCCGAGGATTTTGAAAGGCAGT>AF402668AAATGTAGCAATGCAGCATGGCCTCGTGTCCGAGGATTTTGAAAGGCAGT551600NC_001463(gag)TGGCATATTATGCTACTACCTGGACAAGTAAAGACATACTAGAAGTATTG>AF402664TAGTATATTATGCTACTACCTGGACAAGTAAAGATATATTAGAAGTATTG>AF402665TAGCATATTATGCTACTACCTGGACAAGTAAAGATATATTAGAAGTATTG>AF402666TGGCATATTATGCTACTACCTGGACAAGTAAAGATATATTAGAAGTATTG>AF402667TAGCATATTATGCTACTACCTGGACAAGTAAAGATATATTAGAAGTATTG>AF402668TAGCATATTATGCTACTACCTGGACAAGTAAAGATATATTAGAAGTATTG601650NC_001463(gag)GCCATGATGCCTGGAAATAGAGCTCAAAAGGAGTTAATTCAAGGGAAATT>AF402664GCCATGATGCCTGGAAATAGAGCTCAAAAAGAGTTAATTCAAGGGAAATT>AF402665GCCATGATGCCTGGAAATAGAGCTCAAAAAGAGTTAATTCAAGGGAAATT>AF402666GCCATGATGCCTGGAAACAGAGCTCAAAAAGAGTTAATTCAGGGGAAATT>AF402667GCCATGATGCCTGGAAATAGAGCTCAAAAAGAGTTAATTCAAGGGAAATT>AF402668GCCATGATGCCTGGAAATAGAGCTCAAAAAGAGTTAATTCAAGGGAAATT651700NC_001463(gag)AAATGAAGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCTCCAGCAG>AF402664GAATGAGGAAGCAGAAAGGTGGAGAAGAAATAATCCACCACCTCAAGCAG>AF402665GAATGAGGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCTCAAGCAG>AF402666GAATAAGGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCTCAAGCAC>AF402667GAATGAGGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCTCAAGCAG>AF402668GAATGAGGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCTCAAGCAG701750NC_001463(gag)GAGGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAA>AF402664GCGGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAA>AF402665GCGGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAA>AF402666AAGGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAG>AF402667GCGGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAA>AF402668GCGGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAA751800NC_001463(gag)GCAGCAGCACAAGCTAACATGGATCAGGCAAGGCAAATATGCCTGCAATG>AF402664GCAGCGGCACAGGCTAACATGGATCAGGCAAGACAAATATGTCTGCAATG>AF402665GCAGCGGCACAGGCTAACATGGATCAGGCAAGACAAATATGCCTGCAATG>AF402666GCAGCGGCACAGGCTAACATGGATCAGGCAAGACAAATATGCCTGCAATG>AF402667GCAGCGGCACAGGCTAACATGGATCAGGCAAGACAAATATGCCTGCAATG>AF402668GCAGCGGCACAGGCTAACATGGATCAGGCAAGACAAATATGCCTGCAATG801850NC_001463(gag)GGTAATAAATGCATTAAGAGCAGTAAGACATATGGCGCACAGGCCAGGGA>AF402664GGTAATAACAGCACTAAGAGCAGTGAGACATATGGCTCACAAACCAGGGA>AF402665GGTAATAACAGCACTAAGAGCAGTGAGACATATGGCTCACAAACCAGGGA>AF402666GGTAATAACAGCACTAAGAGCAGTGAGACATATGGCTCACAAACCAGGGA>AF402667GGTAATAACAGCACTAAGAGCAGTGAGACATATGGCTCACAAACCAGGGA>AF402668GGTAATAACAGCACTAAGAGCAGTGAGACATATGGCTCACAAACCAGGGA851900NC_001463(gag)ATCCAATGCTAGTAAAGCAAAAAACGAATGAGCCATATGAAGATTTTGCA>AF402664ATCCAATGCTAGTAAAGCAAAAAACAAATGAGTCATATGAAGATTTTGCC>AF402665ATCCAATGCTAGTAAAGCAAAAGACAAATGAGTCATATGAAGATTTTGCC>AF402666ATCCAATGCTAGTAAAGCAAAAGACAAATGAGTCATATGAAGATTTTGCC>AF402667ATCCAATGCTAGTAAAGCAAAAGACAAATGAGTCATATGAAGATTTTGCC>AF402668ATCCAATGCTAGTAAAGCAAAAGACAAATGAGTCATATGAAAAATTTTCA901950NC_001463(gag)GCAAGACTGCTAGAAGCAATAGATGCAGAGCCAGTTACACAGCCTATAAA>AF402664GCAAGACTGCTAGAAGCAATAGATGCAGAACCAGTTACACAGCAAATAAA>AF402665GCAAGACTGCTAGAAGCAATAGATGCAGAACCAGTTACACAGCAAATAAA>AF402666GCAAGACTGCTAGAAGCAATAGATGCAGAACCAGTTACACAGCAAATAAA>AF402667GCAAGACTGCTAGAAGCAATAGATGCAGAACCAGTTACACAGCAAATAAA>AF402668GCAAGACTCCTAGAAGCAATAGATGCAGAACCAGTTACACAGCCTATAAA9511000NC_001463(gag)AGATTATCTAAAGCTAACACTATCTTATACAAATGCATCAGCAGATTGTC>AF402664AGAATATTTAAAGTTAACATTATCTTACACAAATGCATCCTCAGACTGTC>AF402665AGAATATTTAAAGTTAACATTATCTTACACAAATGCATCCTCAGACTGTC>AF402666AGAATATTTAAAGTTAACATTATCTTACACAAATGCATCCTCAGACTGTC>AF402667.GAATATTTAA.......................................>AF402668AGAATATTTAAAGTTAACATTATCTTACACAAATGCATCCTCAGACTGTC10011050NC_001463(gag)AGAAGCAAATGGATAGAACACTAGGACAAAGAGTACAACAAGCTAGTGTA>AF402664AGAAACAGATGGATAGAGTACTAGGACAGAGAGTGCAACAAGCTAGTGTG>AF402665AAAAACAAATGGATAGAATACTAGGACAGAGAGTGCAACAAGCTAGTGTG>AF402666AGAAACAAATGGATAGAGTACTAGGACAGAGAGTGCAACAAGCTAGTGTG>AF402667..................................................>AF402668AAAAACAAATGGATAGAGTACTAGGACAGAGAGTGCAACAAGCTAGTGTG10511100NC_001463(gag)GAAGAAAAAATGCAAGCATGTAGAGATGTGGGATCAGAAGGGTTCAAAAT>AF402664GAAGAAAAAATGCAAGCATGCAGAGATGTGGGATCAGAAGGATTCAGAAT>AF402665GAAGAAAAAATGCAAGCATGCAGAGATGTGGGATCAGAAGGGTTCAGAAT>AF402666GAAGAAAAAATGCAAGCATGCAGAGATGTGGGATCAGAAGG.........>AF402667..................................................>AF402668GAAGAAAAAATGCAAGCATGCAGAGATGTGGGATCAGAAGGATTCAGAAT11011150NC_001463(gag)GCAATTGTTAGCACAAGCATTAAGGCCAGGAAAAGGAAAAGGGAATGGAC>AF402664GC................................................>AF402665GC................................................>AF402666..................................................>AF402667..................................................>AF402668GC................................................11511200NC_001463(gag)AGCCACAAAGGTGTTACAACTGTGGAAAACCGGGACATCAAGCAAGGCAA>AF402664..................................................>AF402665..................................................>AF402666..................................................>AF402667..................................................>AF402668..................................................12011250NC_001463(gag)TGTAGACAAGGAATCATATGTCACAACTGTGGAAAGAGAGGACATATGCA>AF402664..................................................>AF402665..................................................>AF402666..................................................>AF402667..................................................>AF402668..................................................12511300NC_001463(gag)AAAAGAATGCAGAGGAAAGAGAGACATAAGGGGAAAACAGCAGGGAAACG>AF402664..................................................>AF402665..................................................>AF402666..................................................>AF402667..................................................>AF402668..................................................13011347NC_001463(gag)GGAGGAGGGGGATACGTGTGGTGCCGTCCGCTCCTCCTATGGAATAA>AF402664...............................................>AF402665...............................................>AF402666...............................................>AF402667...............................................>AF402668...............................................表9PileUpMSF742TypeNCheck6523..NameNC_001463(gag720bp)(SEQIDNO31)Len742Check3818Weight0Name>AJ305040(SEQIDNO32)Len742Check1263Weight0Name>AJ305041(SEQIDNO33)Len742Check9126Weight0Name>AJ305042(SEQIDNO34)Len742Check2316Weight0//150NC_001463(gag720bp)ATGGTGAGTCTAGATAGAGACATGGCGAGGCAAGTCTC..CGGGGGGAAA>AJ305040......GCAGTCGATGCTGTAATGTTCCAGCAAATGCAAACAGTAGCCAT>AJ305041......GCAGTAGACTCAGTAATGTTCCAGCAACTGCAAACAGTAGCAAT>AJ305042......GCAGTCGATGCTGTAATGTTCCAGCAAATGCAAACAGTAGCCAT51100NC_001463(gag720bp)AGAGATTATCCTGAGCTCGAAAAATGTATCAAGCATGCATGCAAGATAAA>AJ305040GCAGCATGGTCTTGTGTCTGAGGACTTTGAAAGGCAGTTAGCAT.ATTGT>AJ305041GCAGCATGGCCTCGTGTCCGAGGATTTTGAAAGGCAGTTGGCAT.ATTAT>AJ305042GCAGCATGGTCTTGTGTCTGAGGACTTTGAAAGGCAGTTAGCAT.ATTAT101150NC_001463(gag720bp)AGTTCGACTCAGAGGGG..AGCACTTGACAGAAGGAAATTGTTTATGGTG>AJ305040GCTACTACCTGGACAAGTAAAGATATATTAGAAGTA..TTGGCCATGATG>AJ305041GCTACTACCTGGACGAGTAAAGACATACTAGAAGTA..TTGGCCATGATG>AJ305042GCTACTACCTGGACAAGTAAAGATATATTAGAAGTA..TTGGCCATGATG151200NC_001463(gag720bp)CCTTAAAACATTAGATTACATGTTTGAGGACCATAAAGAGGAACCTTGGA>AJ305040CCTGGAAATAG.AGCTCAAAAA...GAGTTAATTCAAG.GAAAATTAAAC>AJ305041CCTGGAAACAG.AGCTCAAAAG...GAGTTAATTCAAG.GGAAATTAAAT>AJ305042CCTGGAAATAG.AGCTCAAAAA...GAGTTAATTCAAG.GAAAATTAAAT201250NC_001463(gag720bp)CAAAAGTAAAATTTAGGACAATATGGCAGAAGGTGAAGAATCTAACTCCT>AJ305040GAGGAAGCAGAA..AGGTGGAGAAGGAATAA..TCCACCGCCTCCACAAG>AJ305041GAAGAGGCAGAA..AGGTGGAGAAGACATAA..TCCACCCCCTCCGGCGG>AJ305042GAGGAAGCAGAA..AGGTGGAGAAGGAATAA..TCCACCGCCTCCACAGG251300NC_001463(gag720bp)GAGGAG.AGTAACAAAAAAG.ACTTTATGTCTTTGCAGGCCACATTAGCG>AJ305040GAGGGGGATTAACAGTGGATCAAATTATGGGGAT..AGGACAAACAAATC>AJ305041GAGGAGGATTAACAGTGGATCAAATTATGGGGGT..AGGACAAACAAATC>AJ305042GAGGGGGATTAACAGTGGATCAAATTATGGGGAT..AGGACAAACAAATC301350NC_001463(gag720bp)GGTCTAATGTGTTGCCAAATGGGGATGAGACCTGAGACAT.....TGCAA>AJ305040AAGCAGCAGCACAAGCTAACATGGATCAGGCAAGACACATATGCCTGCAA>AJ305041AAGCAGCAGCACAAGCTAACATGGATCAGGCAAGACAAATATGCCTGCAA>AJ305042AAGCAGCAGCACAAGCTAACATGGATCAGGCAAGACACATATGCCTGCAA351400NC_001463(gag720bp)GATGCAATGGCTACAGTAAT..CA.TGAAAGATGGGTTACTGGAACAAGA>AJ305040TGGGTAATAACAGCATTAAGAGCAGTAAGACATATGGCTCACAGACCAGG>AJ305041TGGGTAATAACAGCATTAAGAGCAGTGAGGTATATGACTCACAAACCAGG>AJ305042TGGGTAATAACAGCATTAAGAGCAGTAAGACATATGGCTCACAGACCAGG401450NC_001463(gag720bp)GGA...AAAGA.AGGAAGACAAAAGAGAAAAGGAAGAGAGT..GTCTTCC>AJ305040GAATCCAATGCTCGTAAAACAAAAAACAAATGAGCCATATGAAGAGTTTG>AJ305041GAATCCAATGCTAGTAAAACAAAAAACAAATGAAGCATATGAAGAGTTTA>AJ305042GAATCCAATGCTCGTAAAACAAAAAACAAATGAGCCATATGAAGAGTTTG451500NC_001463(gag720bp)CAATAGTAGTGCAAGCAGCAGGAG..GGAGAAGCTGGAAAGCAGTAGATT>AJ305040CAGCAAAACTATTAGAAGCAATAGATGCAGAACCAGTAACACAGCCCATA>AJ305041CAGCGAGACTGCTAGAAGCAATAGATGCAGAGCCAGTAACACAGCCCACA>AJ305042CAGCAAAACTATTAGAAGCAATAGATGCAGAACCAGTAACACAGCTCATA501550NC_001463(gag720bp)CTGTAATGTTCCAGCAACTGCAAACAGTAGCAATGCAGCATGGCCTCGTG>AJ305040AAAGACTAT..CTAAAGTT...AACATTATCT.TATACAAATGCGTC...>AJ305041AAAGAATAT..CTAAAACT...AACATTATCT.TATACAAATGCATC...>AJ305042AAAGACTAT..CTAAAGTT...AACATTATCT.TATACAAATGCGTC...551600NC_001463(gag720bp)TCTGAGGACTTTGAAAGGCAGTTGGCATATTATGCTACTACCTGGACAAG>AJ305040.CTCAG.ACTGTCAAAAGCAAATGG.ATAGAGTGCTGGGACAAAG...AG>AJ305041.CTCAG.ACTGTCAAAAGCAAATGG.ATAGAGTACTAGGACAAAG...AG>AJ305042.CTCAG.ACTGTCAAAAGCAAATGG.ATAGAGTGCTGGGACAAAG...AG601650NC_001463(gag720bp)TAAAGACATACTAGAAGTATTGGCCATGATGCCTGGAAATAGAGCTCAAA>AJ305040TGCA.ACAAGCTAGT.GTAGACGAGAAAATGCAA................>AJ305041TGCA.ACAAGCTAGT.GTAGAAGAAAAAATGCAA................>AJ305042TGCA.ACAAGCTAGT.GTAGACGAGAAGATGCAA................651700NC_001463(gag720bp)AGGAGTTAATTCAAGGGAAATTAAATGAAGAAGCAGAAAGGTGGAGAAGG>AJ305040..................................................>AJ305041..................................................>AJ305042..................................................701742NC_001463(gag720bp)AATAATCCACCACCTCCAGCAGGAGGAGGATTAACAGTGGAT>AJ305040..........................................>AJ305041..........................................>AJ305042..........................................PileUpMSF1347TypeNCheck9510..NameNC_001463(gag)(SEQIDNO35)Len1347Check6959Weight0Name>AJ305040(SEQIDNO36)Len1347Check1930Weight0Name>AJ305041(SEQIDNO37)Len1347Check7682Weight0Name>AJ305042(SEQIDNO38)Len1347Check2939Weight0//150NC_001463(gag)ATGGTGAGTCTAGATAGAGACATGGCGAGGCAAGTCTCCGGGGGGAAAAG>AJ305040..................................................>AJ305041..................................................>AJ305042..................................................51100NC_001463(gag)AGATTATCCTGAGCTCGAAAAATGTATCAAGCATGCATGCAAGATAAAAG>AJ305040..................................................>AJ305041..................................................>AJ305042..................................................101150NC_001463(gag)TTCGACTCAGAGGGGAGCACTTGACAGAAGGAAATTGTTTATGGTGCCTT>AJ305040..................................................>AJ305041..................................................>AJ305042..................................................151200NC_001463(gag)AAAACATTAGATTACATGTTTGAGGACCATAAAGAGGAACCTTGGACAAA>AJ305040..................................................>AJ305041..................................................>AJ305042..................................................201250NC_001463(gag)AGTAAAATTTAGGACAATATGGCAGAAGGTGAAGAATCTAACTCCTGAGG>AJ305040..................................................>AJ305041..................................................>AJ305042..................................................251300NC_001463(gag)AGAGTAACAAAAAAGACTTTATGTCTTTGCAGGCCACATTAGCGGGTCTA>AJ305040..................................................>AJ305041..................................................>AJ305042..................................................301350NC_001463(gag)ATGTGTTGCCAAATGGGGATGAGACCTGAGACATTGCAAGATGCAATGGC>AJ305040..................................................>AJ305041..................................................>AJ305042..................................................351400NC_001463(gag)TACAGTAATCATGAAAGATGGGTTACTGGAACAAGAGGAAAAGAAGGAAG>AJ305040..................................................>AJ305041..................................................>AJ305042..................................................401450NC_001463(gag)ACAAAAGAGAAAAGGAAGAGAGTGTCTTCCCAATAGTAGTGCAAGCAGCA>AJ305040..................................................>AJ305041..................................................>AJ305042..................................................451500NC_001463(gag)GGAGGGAGAAGCTGGAAAGCAGTAGATTCTGTAATGTTCCAGCAACTGCA>AJ305040..................GCAGTCGATGCTGTAATGTTCCAGCAAATGCA>AJ305041..................GCAGTAGACTCAGTAATGTTCCAGCAACTGCA>AJ305042..................GCAGTCGATGCTGTAATGTTCCAGCAAATGCA501550NC_001463(gag)AACAGTAGCAATGCAGCATGGCCTCGTGTCTGAGGACTTTGAAAGGCAGT>AJ305040AACAGTAGCCATGCAGCATGGTCTTGTGTCTGAGGACTTTGAAAGGCAGT>AJ305041AACAGTAGCAATGCAGCATGGCCTCGTGTCCGAGGATTTTGAAAGGCAGT>AJ305042AACAGTAGCCATGCAGCATGGTCTTGTGTCTGAGGACTTTGAAAGGCAGT551600NC_001463(gag)TGGCATATTATGCTACTACCTGGACAAGTAAAGACATACTAGAAGTATTG>AJ305040TAGCATATTGTGCTACTACCTGGACAAGTAAAGATATATTAGAAGTATTG>AJ305041TGGCATATTATGCTACTACCTGGACGAGTAAAGACATACTAGAAGTATTG>AJ305042TAGCATATTATGCTACTACCTGGACAAGTAAAGATATATTAGAAGTATTG601650NC_001463(gag)GCCATGATGCCTGGAAATAGAGCTCAAAAGGAGTTAATTCAAGGGAAATT>AJ305040GCCATGATGCCTGGAAATAGAGCTCAAAAAGAGTTAATTCAAGGAAAATT>AJ305041GCCATGATGCCTGGAAACAGAGCTCAAAAGGAGTTAATTCAAGGGAAATT>AJ305042GCCATGATGCCTGGAAATAGAGCTCAAAAAGAGTTAATTCAAGGAAAATT651700NC_001463(gag)AAATGAAGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCTCCAGCAG>AJ305040AAACGAGGAAGCAGAAAGGTGGAGAAGGAATAATCCACCGCCTCCACAAG>AJ305041AAATGAAGAGGCAGAAAGGTGGAGAAGACATAATCCACCCCCTCCGGCGG>AJ305042AAATGAGGAAGCAGAAAGGTGGAGAAGGAATAATCCACCGCCTCCACAGG701750NC_001463(gag)GAGGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAA>AJ305040GAGGGGGATTAACAGTGGATCAAATTATGGGGATAGGACAAACAAATCAA>AJ305041GAGGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAA>AJ305042GAGGGGGATTAACAGTGGATCAAATTATGGGGATAGGACAAACAAATCAA751800NC_001463(gag)GCAGCAGCACAAGCTAACATGGATCAGGCAAGGCAAATATGCCTGCAATG>AJ305040GCAGCAGCACAAGCTAACATGGATCAGGCAAGACACATATGCCTGCAATG>AJ305041GCAGCAGCACAAGCTAACATGGATCAGGCAAGACAAATATGCCTGCAATG>AJ305042GCAGCAGCACAAGCTAACATGGATCAGGCAAGACACATATGCCTGCAATG801850NC_001463(gag)GGTAATAAATGCATTAAGAGCAGTAAGACATATGGCGCACAGGCCAGGGA>AJ305040GGTAATAACAGCATTAAGAGCAGTAAGACATATGGCTCACAGACCAGGGA>AJ305041GGTAATAACAGCATTAAGAGCAGTGAGGTATATGACTCACAAACCAGGGA>AJ305042GGTAATAACAGCATTAAGAGCAGTAAGACATATGGCTCACAGACCAGGGA851900NC_001463(gag)ATCCAATGCTAGTAAAGCAAAAAACGAATGAGCCATATGAAGATTTTGCA>AJ305040ATCCAATGCTCGTAAAACAAAAAACAAATGAGCCATATGAAGAGTTTGCA>AJ305041ATCCAATGCTAGTAAAACAAAAAACAAATGAAGCATATGAAGAGTTTACA>AJ305042ATCCAATGCTCGTAAAACAAAAAACAAATGAGCCATATGAAGAGTTTGCA901950NC_001463(gag)GCAAGACTGCTAGAAGCAATAGATGCAGAGCCAGTTACACAGCCTATAAA>AJ305040GCAAAACTATTAGAAGCAATAGATGCAGAACCAGTAACACAGCCCATAAA>AJ305041GCGAGACTGCTAGAAGCAATAGATGCAGAGCCAGTAACACAGCCCACAAA>AJ305042GCAAAACTATTAGAAGCAATAGATGCAGAACCAGTAACACAGCTCATAAA9511000NC_001463(gag)AGATTATCTAAAGCTAACACTATCTTATACAAATGCATCAGCAGATTGTC>AJ305040AGACTATCTAAAGTTAACATTATCTTATACAAATGCGTCCTCAGACTGTC>AJ305041AGAATATCTAAAACTAACATTATCTTATACAAATGCATCCTCAGACTGTC>AJ305042AGACTATCTAAAGTTAACATTATCTTATACAAATGCGTCCTCAGACTGTC10011050NC_001463(gag)AGAAGCAAATGGATAGAACACTAGGACAAAGAGTACAACAAGCTAGTGTA>AJ305040AAAAGCAAATGGATAGAGTGCTGGGACAAAGAGTGCAACAAGCTAGTGTA>AJ305041AAAAGCAAATGGATAGAGTACTAGGACAAAGAGTGCAACAAGCTAGTGTA>AJ305042AAAAGCAAATGGATAGAGTGCTGGGACAAAGAGTGCAACAAGCTAGTGTA10511100NC_001463(gag)GAAGAAAAAATGCAAGCATGTAGAGATGTGGGATCAGAAGGGTTCAAAAT>AJ305040GACGAGAAAATGCAA...................................>AJ305041GAAGAAAAAATGCAA...................................>AJ305042GACGAGAAGATGCAA...................................11011150NC_001463(gag)GCAATTGTTAGCACAAGCATTAAGGCCAGGAAAAGGAAAAGGGAATGGAC>AJ305040..................................................>AJ305041..................................................>AJ305042..................................................11511200NC_001463(gag)AGCCACAAAGGTGTTACAACTGTGGAAAACCGGGACATCAAGCAAGGCAA>AJ305040..................................................>AJ305041..................................................>AJ305042..................................................12011250NC_001463(gag)TGTAGACAAGGAATCATATGTCACAACTGTGGAAAGAGAGGACATATGCA>AJ305040..................................................>AJ305041..................................................>AJ305042..................................................12511300NC_001463(gag)AAAAGAATGCAGAGGAAAGAGAGACATAAGGGGAAAACAGCAGGGAAACG>AJ305040..................................................>AJ305041..................................................>AJ305042..................................................13011347NC_001463(gag)GGAGGAGGGGGATACGTGTGGTGCCGTCCGCTCCTCCTATGGAATAA>AJ305040..................................................>AJ305041..................................................>AJ305042..................................................表10PileUpMSF728TypeNCheck9403..NameNC_001463(gag720bp)(SEQIDNO39)Len728Check5765Weight0Name>AY047362(SEQIDNO40)Len728Check3638Weight0//150NC_001463(gag720bp)ATGGTGAGTCTAGATAGAGACATGGCGAGGCAAGTCTCCGGGGGGAAAAG>AY047362..................................................51100NC_001463(gag720bp)AGATTATCCTGAGCTCGAAAAATGTATCAAGCATGCATGCAAGATAAAAG>AY047362......TAAAGATATATTAGAA.GTATTGGCCATG.ATGCCTGGAAATAG101150NC_001463(gag720bp)TTCGACTCAGAGGGGAGCACTTGACAGAAGGAAATTGTTTATGGTGCCTT>AY047362AGC...TCAAAAAGAGTTAATTCA...AGGGAAATTGAATGAAGAAGCAG151200NC_001463(gag720bp)AAAACATTAGATTACATGTTTGAGGACCATAAAGAGGAACCTTGGACAAA>AY047362AAAGGTGGAGAAGGAATAATCCACCACCTCAAGCAGG..CGGAGGATTAA201250NC_001463(gag720bp)AGTAAAATTTAGGACAATATGGCAGAAGGTGAAG..AATCTAACTCCTGA>AY047362C..AG..TGGATCAAATTATGGGGGTAGGACAAACAAATCAAGCAGCGGC251300NC_001463(gag720bp)GGAGAGTAACAAAAAAGACTTTATGTCTTTGCAGGCCACATTAGCGGGTC>AY047362ACAGGCTAACATGGATCAG...........GCAAGACAAATATGC..CTG301350NC_001463(gag720bp)TAATGTGTTGCCAAATGGGGATGAGACCTGAGACATTGCAAGATGCAATG>AY047362CAATGGGTAATAACAGCACTAAGAGCAGTGAGACAT......A.....TG351400NC_001463(gag720bp)GCTACAGTAATCATGAAAGATGGGTTACTGGAACAAGAGGAAAAGAAGGA>AY047362GCT.CACAAACCAGGGA..ATCCGATGCT......AGT..AAAGCAA..A401450NC_001463(gag720bp)AGACAAAAGAGAAA.AGGAAGAGAGTGTCTTCCCAATAGTAGTGCAAGCA>AY047362AAACAAATGAGTCATATGAAGATTTTGCCG...CAAGACTGCTAGAAGCA451500NC_001463(gag720bp)GCAGGAGGGAGAAGCTGGAAAGCAGTAGATTCTGTAATGTTCCAGCAACT>AY047362ATAG.ATGCAGAACCAGTTACAAAGCAAATAAAAGAATATTT.....AAA501550NC_001463(gag720bp)GCAAACAGTAGCAATGCAGCATGGCCTCGTGTCTGAGGACTTTGAAAGGC>AY047362GTTAACATTATCT.TACACAAATGCATC....CTCAG.ACTGTAAGAAAC551600NC_001463(gag720bp)AGTTGGCATATTATGCTACTACCTGGACAAGTA.AAGACATACTAGAAGT>AY047362AGATGG.ATAGAGTACTAGGACAGAGAGTGCAACAAGCTAGTGTGGAAGA601650NC_001463(gag720bp)ATTG..GCCATGATGCCTGGAAATAGAGCTCAAAAGGAGTTA..ATTCAA>AY047362AAAAATGCAAGCATGCAGAGATGT.GGGATCAGAAGGATTCAGAATGC..651700NC_001463(gag720bp)GGGAAATTAAATGAAGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACC>AY047362..................................................701728NC_001463(gag720bp)TCCAGCAGGAGGAGGATTAACAGTGGAT>AY047362............................PileUpMSF1347TypeNCheck3238..NameNC_001463(gag)(SEQIDNO41)Len1347Check6959Weight0Name>AY047362(SEQIDNO42)Len1347Check6279Weight0//150NC_001463(gag)ATGGTGAGTCTAGATAGAGACATGGCGAGGCAAGTCTCCGGGGGGAAAAG>AY047362..................................................51100NC_001463(gag)AGATTATCCTGAGCTCGAAAAATGTATCAAGCATGCATGCAAGATAAAAG>AY047362..................................................101150NC_001463(gag)TTCGACTCAGAGGGGAGCACTTGACAGAAGGAAATTGTTTATGGTGCCTT>AY047362..................................................151200NC_001463(gag)AAAACATTAGATTACATGTTTGAGGACCATAAAGAGGAACCTTGGACAAA>AY047362..................................................201250NC_001463(gag)AGTAAAATTTAGGACAATATGGCAGAAGGTGAAGAATCTAACTCCTGAGG>AY047362..................................................251300NC_001463(gag)AGAGTAACAAAAAAGACTTTATGTCTTTGCAGGCCACATTAGCGGGTCTA>AY047362..................................................301350NC_001463(gag)ATGTGTTGCCAAATGGGGATGAGACCTGAGACATTGCAAGATGCAATGGC>AY047362..................................................351400NC_001463(gag)TACAGTAATCATGAAAGATGGGTTACTGGAACAAGAGGAAAAGAAGGAAG>AY047362..................................................401450NC_001463(gag)ACAAAAGAGAAAAGGAAGAGAGTGTCTTCCCAATAGTAGTGCAAGCAGCA>AY047362..................................................451500NC_001463(gag)GGAGGGAGAAGCTGGAAAGCAGTAGATTCTGTAATGTTCCAGCAACTGCA>AY047362..................................................501550NC_001463(gag)AACAGTAGCAATGCAGCATGGCCTCGTGTCTGAGGACTTTGAAAGGCAGT>AY047362..................................................551600NC_001463(gag)TGGCATATTATGCTACTACCTGGACAAGTAAAGACATACTAGAAGTATTG>AY047362............................TAAAGATATATTAGAAGTATTG601650NC_001463(gag)GCCATGATGCCTGGAAATAGAGCTCAAAAGGAGTTAATTCAAGGGAAATT>AY047362GCCATGATGCCTGGAAATAGAGCTCAAAAAGAGTTAATTCAAGGGAAATT651700NC_001463(gag)AAATGAAGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCTCCAGCAG>AY047362GAATGAAGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCTCAAGCAG701750NC_001463(gag)GAGGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAA>AY047362GCGGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAA751800NC_001463(gag)GCAGCAGCACAAGCTAACATGGATCAGGCAAGGCAAATATGCCTGCAATG>AY047362GCAGCGGCACAGGCTAACATGGATCAGGCAAGACAAATATGCCTGCAATG801850NC_001463(gag)GGTAATAAATGCATTAAGAGCAGTAAGACATATGGCGCACAGGCCAGGGA>AY047362GGTAATAACAGCACTAAGAGCAGTGAGACATATGGCTCACAAACCAGGGA851900NC_001463(gag)ATCCAATGCTAGTAAAGCAAAAAACGAATGAGCCATATGAAGATTTTGCA>AY047362ATCCGATGCTAGTAAAGCAAAAAACAAATGAGTCATATGAAGATTTTGCC901950NC_001463(gag)GCAAGACTGCTAGAAGCAATAGATGCAGAGCCAGTTACACAGCCTATAAA>AY047362GCAAGACTGCTAGAAGCAATAGATGCAGAACCAGTTACAAAGCAAATAAA9511000NC_001463(gag)AGATTATCTAAAGCTAACACTATCTTATACAAATGCATCAGCAGATTGTC>AY047362AGAATATTTAAAGTTAACATTATCTTACACAAATGCATCCTCAGACTGTA10011050NC_001463(gag)AGAAGCAAATGGATAGAACACTAGGACAAAGAGTACAACAAGCTAGTGTA>AY047362AGAAACAGATGGATAGAGTACTAGGACAGAGAGTGCAACAAGCTAGTGTG10511100NC_001463(gag)GAAGAAAAAATGCAAGCATGTAGAGATGTGGGATCAGAAGGGTTCAAAAT>AY047362GAAGAAAAAATGCAAGCATGCAGAGATGTGGGATCAGAAGGATTCAGAAT11011150NC_001463(gag)GCAATTGTTAGCACAAGCATTAAGGCCAGGAAAAGGAAAAGGGAATGGAC>AY047362GC................................................11511200NC_001463(gag)AGCCACAAAGGTGTTACAACTGTGGAAAACCGGGACATCAAGCAAGGCAA>AY047362..................................................12011250NC_001463(gag)TGTAGACAAGGAATCATATGTCACAACTGTGGAAAGAGAGGACATATGCA>AY047362..................................................12511300NC_001463(gag)AAAAGAATGCAGAGGAAAGAGAGACATAAGGGGAAAACAGCAGGGAAACG>AY047362..................................................13011347NC_001463(gag)GGAGGAGGGGGATACGTGTGGTGCCGTCCGCTCCTCCTATGGAATAA>AY047362...............................................表11PileUpMSF733TypeNCheck5855..NameNC_001463(gag720bp)(SEQIDNO43)Len733Check9482Weight0Name>AY081139(SEQIDNO44)Len733Check6373Weight0//150NC_001463(gag720bp)ATGGTGAGTCTAGATAGAGACATGGCGAGGCAAGTCTCCGGGGGGAAAAG>AY081139....................................TGCCGTAGACTCTG51100NC_001463(gag720bp)AGATTATCCTG.AGCTCGAAAAATGTATCAAGCATGCATGCAAGATAAAA>AY081139TGATGTTCCACCAGCT.GCATACAGTAGCAATGCCGCATGGCCTCGTGTC101150NC_001463(gag720bp)GTTCGACTCAGAGGGGAGCACTTGACAGAAGGAAATTGTTTATGGTGCCT>AY081139TGAGGACTTTGAAAGG..CAGTTGGCATATTATGCTACTACCTGGACAAG151200NC_001463(gag720bp)TAAAACATTAGATTACATGT.TTGAGGACCATAAAGAGGAACCTTGGACA>AY081139TAAAGA..TATACTGGAAGTATTGGCCATGATGCCTGGGAATAGAGCTCA201250NC_001463(gag720bp)AAAGTAA..AATTTAGGACAATATGGCAGAAGGTGAAGAATCTAACTCCT>AY081139AAAAGAATTAATTCAAGGAAAATTAAATGAAGAAGCAGAA..........251300NC_001463(gag720bp)GAGGAGAGTAACAAAAAAGACTTTATGTCTTTGCAGGCCACATTAGCGGG>AY081139.AGGTGGAGAAGGAATAATCCACCACCTCAA.GCAGGCG......GAGGA301350NC_001463(gag720bp)TCTAATGTGTTGCCAA..ATGGGGATGAGACCTGAGACATTGCAAGATGC>AY081139TTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAAGCAGCTGC351400NC_001463(gag720bp)AATGGCTA.CAGTAATCATGAAAGATGGGTTACTGGAACAAGAGGAAAAG>AY081139ACAAGCTAACATGGATCAGGCAAGACAAATA..TGCCTGCAATGGGTAAT401450NC_001463(gag720bp)AAGGAAGACAAAAGAGAAAAGGAAGAGAGTGTCTTCCCAATAGTAGTGCA>AY081139ATC..AGCCTTAAGAGCAGTGAGACATA.TGTCT..CATAAACCAGGG.A451500NC_001463(gag720bp)AGCAGCAGGAGGGAGAAGCTGGAAAGCAGTAGATTCTGTAATGTTCCAGC>AY081139ATCCGCTGCTAGTA.AAGCAAAAAACAAATGAGTCATATGAAGATTTTGC501550NC_001463(gag720bp)AACTGCAAAC..AGTAGCAATGCAGCATGGCCTCGTGTCTGAGGACTTTG>AY081139AGCTAGACTGCTAGAAGCAATAGATCCAGCCCCAGTAGCACATC.CTATA551600NC_001463(gag720bp)AAAGGCAGTTGGCATATTATGCTAC....TACCTGGACAAGTAAAGACAT>AY081139AAAGATTATTTAAAGTTAACACTATCTTATACGAATGCATCATCAGATTG601650NC_001463(gag720bp)ACTAGAAGTATTGGCCATGATGCCTGGAAATAGAGCTCAAAAGGAGTTAA>AY081139TCAAAAGCAAATGGGTAGAATGCTAGGATCGAGAGTCCATCA..AGCCAG651700NC_001463(gag720bp)TTCAAGGGAAATTAAATGAAGAAGCAGAAAGGTGGAGAAGGAATAATCCA>AY081139TGTGGGCCAAAAAA....................................701733NC_001463(gag720bp)CCACCTCCAGCAGGAGGAGGATTAACAGTGGAT>AY081139.................................PileUpMSF1347TypeNCheck2072..NameNC_001463(gag)(SEQIDNO45)Len1347Check6959Weight0Name>AY081139(SEQIDNO46)Len1347Check5113Weight0//150NC_001463(gag)ATGGTGAGTCTAGATAGAGACATGGCGAGGCAAGTCTCCGGGGGGAAAAG>AY081139..................................................51100NC_001463(gag)AGATTATCCTGAGCTCGAAAAATGTATCAAGCATGCATGCAAGATAAAAG>AY081139..................................................101150NC_001463(gag)TTCGACTCAGAGGGGAGCACTTGACAGAAGGAAATTGTTTATGGTGCCTT>AY081139..................................................151200NC_001463(gag)AAAACATTAGATTACATGTTTGAGGACCATAAAGAGGAACCTTGGACAAA>AY081139..................................................201250NC_001463(gag)AGTAAAATTTAGGACAATATGGCAGAAGGTGAAGAATCTAACTCCTGAGG>AY081139..................................................251300NC_001463(gag)AGAGTAACAAAAAAGACTTTATGTCTTTGCAGGCCACATTAGCGGGTCTA>AY081139..................................................301350NC_001463(gag)ATGTGTTGCCAAATGGGGATGAGACCTGAGACATTGCAAGATGCAATGGC>AY081139..................................................351400NC_001463(gag)TACAGTAATCATGAAAGATGGGTTACTGGAACAAGAGGAAAAGAAGGAAG>AY081139..................................................401450NC_001463(gag)ACAAAAGAGAAAAGGAAGAGAGTGTCTTCCCAATAGTAGTGCAAGCAGCA>AY081139..................................................451500NC_001463(gag)GGAGGGAGAAGCTGGAAAGCAGTAGATTCTGTAATGTTCCAGCAACTGCA>AY081139.................TGCCGTAGACTCTGTGATGTTCCACCAGCTGCA501550NC_001463(gag)AACAGTAGCAATGCAGCATGGCCTCGTGTCTGAGGACTTTGAAAGGCAGT>AY081139TACAGTAGCAATGCCGCATGGCCTCGTGTCTGAGGACTTTGAAAGGCAGT551600NC_001463(gag)TGGCATATTATGCTACTACCTGGACAAGTAAAGACATACTAGAAGTATTG>AY081139TGGCATATTATGCTACTACCTGGACAAGTAAAGATATACTGGAAGTATTG601650NC_001463(gag)GCCATGATGCCTGGAAATAGAGCTCAAAAGGAGTTAATTCAAGGGAAATT>AY081139GCCATGATGCCTGGGAATAGAGCTCAAAAAGAATTAATTCAAGGAAAATT651700NC_001463(gag)AAATGAAGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCTCCAGCAG>AY081139AAATGAAGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCTCAAGCAG701750NC_001463(gag)GAGGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAA>AY081139GCGGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAA751800NC_001463(gag)GCAGCAGCACAAGCTAACATGGATCAGGCAAGGCAAATATGCCTGCAATG>AY081139GCAGCTGCACAAGCTAACATGGATCAGGCAAGACAAATATGCCTGCAATG801850NC_001463(gag)GGTAATAAATGCATTAAGAGCAGTAAGACATATGGCGCACAGGCCAGGGA>AY081139GGTAATATCAGCCTTAAGAGCAGTGAGACATATGTCTCATAAACCAGGGA851900NC_001463(gag)ATCCAATGCTAGTAAAGCAAAAAACGAATGAGCCATATGAAGATTTTGCA>AY081139ATCCGCTGCTAGTAAAGCAAAAAACAAATGAGTCATATGAAGATTTTGCA901950NC_001463(gag)GCAAGACTGCTAGAAGCAATAGATGCAGAGCCAGTTACACAGCCTATAAA>AY081139GCTAGACTGCTAGAAGCAATAGATCCAGCCCCAGTAGCACATCCTATAAA9511000NC_001463(gag)AGATTATCTAAAGCTAACACTATCTTATACAAATGCATCAGCAGATTGTC>AY081139AGATTATTTAAAGTTAACACTATCTTATACGAATGCATCATCAGATTGTC10011050NC_001463(gag)AGAAGCAAATGGATAGAACACTAGGACAAAGAGTACAACAAGCTAGTGTA>AY081139AAAAGCAAATGGGTAGAATGCTAGGATCGAGAGTCCATCAAGCCAGTGTG10511100NC_001463(gag)GAAGAAAAAATGCAAGCATGTAGAGATGTGGGATCAGAAGGGTTCAAAAT>AY081139GGCCAAAAAA........................................11011150NC_001463(gag)GCAATTGTTAGCACAAGCATTAAGGCCAGGAAAAGGAAAAGGGAATGGAC>AY081139..................................................11511200NC_001463(gag)AGCCACAAAGGTGTTACAACTGTGGAAAACCGGGACATCAAGCAAGGCAA>AY081139..................................................12011250NC_001463(gag)TGTAGACAAGGAATCATATGTCACAACTGTGGAAAGAGAGGACATATGCA>AY081139..................................................12511300NC_001463(gag)AAAAGAATGCAGAGGAAAGAGAGACATAAGGGGAAAACAGCAGGGAAACG>AY081139..................................................13011347NC_001463(gag)GGAGGAGGGGGATACGTGTGGTGCCGTCCGCTCCTCCTATGGAATAA>AY081139..................................................表12PileUpMSF731TypeNCheck9546..NameNC_001463(gag720bp)(SEQIDNO47)Len731Check7595Weight0Name>AY101347(SEQIDNO48)Len731Check7962Weight0Name>AY101348(SEQIDNO49)Len731Check3989Weight0//150NC_001463(gag720bp)ATGGTGAGTCTAGATAGAGACATGGCGAGGCAAGTCTCCGGGGGGAAAAG>AY101347..................................................>AY101348..................................................51100NC_001463(gag720bp)AGATTATCCTGAGCTCGAAAAATGTATCAAGCATGCATGCAAGATAAAAG>AY101347.........................AGCAGTAGATTCTGTAATGTTCCAG>AY101348.........................AGCCGTAGATTCTGTAATGTTCCAG101150NC_001463(gag720bp)TTCGACT.CAGAGGGGAGCACTTGACAGAAGGAAATTGTTTATGGTGCCT>AY101347..CAACTGCAAACAGTAGCAAT..GCAGCATGGACTCGTGTATGAAGACT>AY101348..CAGCTGCAAACAGTAGCAAT..GCAGCATGGCCTCGTGTCAGAGGACT151200NC_001463(gag720bp)TAAAACATTAGATTACATGTTTGAGGACCATAAAGAGGAACCTTGGACAA>AY101347TTGAAAGGCTGTCGGCATATTATGCTACTACCTGGAC.AAGTAAAGATAT>AY101348TTGAAAGGCTTCCAGCATATCATGCTACTACCTGGGC.AAGTAAAGATAT201250NC_001463(gag720bp)AAGTAAAATTTAGGACAATATGGCAGAAGGTGAAGAATCTAACTCCTGAG>AY101347ACTGGAAGTATTGGCCATGATGCCTG..G.....GAATAGAGCTCAAAAA>AY101348CTTAGAAGTACTGGCCATGATGCCTG..G.....AAATAGAGCTCAAAAA251300NC_001463(gag720bp)GAGAGTAA..CAAAAAAGACTTTATGTCTTTGCAGGCCACATTAGCGGGT>AY101347GA.ATTAATTCAAGGAAAATTAAATGAAGAAGCAGAAAGGTGGAGAAGGA>AY101348GA.GTTAATTCAAGGGAAATTAAATGAAGAAGCAGAGAGGTGGAGAAGGA301350NC_001463(gag720bp)CTAATGTGTTGCCAAATGGGGATGAGACCTGAGACATTGCAAGATGCAAT>AY101347ATAATCCACCACCTCAAGCAGGCG.GAGGATTAACAGTGGATCAAATTAT>AY101348ATAATCCACCACCTCCAGCAGGAG.GAGGGTTAACAGTGGATCAAATTAT351400NC_001463(gag720bp)GGCTACAGTAATCATGAAAGATGG.GTTACTGGAACAAGAGGAAAAGAAG>AY101347GGGGGTAGGACAAACAAATCAAGCAGCTGCACAAGCTAACATGGATCAGG>AY101348GGGAGTAGGACAAACAAATCAGGCAGCGGCACAAGCAAACATGGATCAGG401450NC_001463(gag720bp)GAAGACAAAAGAGAAAAGGAAGAG.AGTGTCTTCCC.AATAGTAGTGCAA>AY101347CAAGACAAATATGCCTGCAATGGGTAATATCAGCCTTAAGAGCAGTGAGA>AY101348CAAGACAAATATGCCTACAATGGGTGATATCAGCACTAAGAGCAGTAAGG451500NC_001463(gag720bp)GCAGCAGGAGGGAGAAGCTGGAAAGCAGTAGATTCTGTAATGTTCCAGCA>AY101347.CATATGTCTCATAAACCAGGGAATCCGCTGCTAGTA.AAGCAAAAAACA>AY101348.CATATGGCTCACAAGCCAGGGAATCCAATGTTAGTA.AAGCAAAAAGCA501550NC_001463(gag720bp)ACTG...CAAACAGTAGCAATGCAGCATGGCCTCGTGTCTGAGGACTTTG>AY101347AATGAGTCATATGAAGATTTTGCAGCAAGACTGCTAGAAGCAATAGATGC>AY101348AATGAGCCATATGAAGAATTTGCAGCAAGGCTGCTGGAAGCAATAGATGC551600NC_001463(gag720bp)AAAGGCAGTTGG.CATATTATGCTACTACCTGGACAAGTAAAGAC.ATAC>AY101347AGAGCCAGTAGCACATCCTATAAAAGAATACTTA.AAGTTAACACTATCT>AY101348CGAGCCAGTTAATCAGCCCATAAAAGAATATCTA.AAACTAACGTTGTCT601650NC_001463(gag720bp)TAGAAGTATTGGCCATGATGCCTGGAAATAGAGCTCAAAAGGAGTTAATT>AY101347TATACGAATGCATCATCA.GATTGTCAAAAG....CAAATGGATAGAATG>AY101348TATACGAATGCATCCTCA.GATTGTCAGAAG....CAAATGGATAGAACA651700NC_001463(gag720bp)CAAGGGAAATTAAATGAAGAAGCAGAAAGGTGGAGAAGGAATAATCCACC>AY101347CTGG...AATCAAGAGTACAACAAGCTAG.TGTAGAACAAAAAA......>AY101348CTAG...GACAAAGAGTCAAACAAGCTAG.TGTAGAACAAAAAA......701731NC_001463(gag720bp)ACCTCCAGCAGGAGGAGGATTAACAGTGGAT>AY101347...............................>AY101348...............................PileUpMSF1347TypeNCheck2815..NameNC_001463(gag)(SEQIDNO50)Len1347Check6959Weight0Name>AY101347(SEQIDNO51)Len1347Check969Weight0Name>AY101348(SEQIDNO52)Len1347Check4887Weight0//150NC_001463(gag)ATGGTGAGTCTAGATAGAGACATGGCGAGGCAAGTCTCCGGGGGGAAAAG>AY101347..................................................>AY101348..................................................51100NC_001463(gag)AGATTATCCTGAGCTCGAAAAATGTATCAAGCATGCATGCAAGATAAAAG>AY101347..................................................>AY101348..................................................101150NC_001463(gag)TTCGACTCAGAGGGGAGCACTTGACAGAAGGAAATTGTTTATGGTGCCTT>AY101347..................................................>AY101348..................................................151200NC_001463(gag)AAAACATTAGATTACATGTTTGAGGACCATAAAGAGGAACCTTGGACAAA>AY101347..................................................>AY101348..................................................201250NC_001463(gag)AGTAAAATTTAGGACAATATGGCAGAAGGTGAAGAATCTAACTCCTGAGG>AY101347..................................................>AY101348..................................................251300NC_001463(gag)AGAGTAACAAAAAAGACTTTATGTCTTTGCAGGCCACATTAGCGGGTCTA>AY101347..................................................>AY101348..................................................301350NC_001463(gag)ATGTGTTGCCAAATGGGGATGAGACCTGAGACATTGCAAGATGCAATGGC>AY101347..................................................>AY101348..................................................351400NC_001463(gag)TACAGTAATCATGAAAGATGGGTTACTGGAACAAGAGGAAAAGAAGGAAG>AY101347..................................................>AY101348..................................................401450NC_001463(gag)ACAAAAGAGAAAAGGAAGAGAGTGTCTTCCCAATAGTAGTGCAAGCAGCA>AY101347..................................................>AY101348..................................................451500NC_001463(gag)GGAGGGAGAAGCTGGAAAGCAGTAGATTCTGTAATGTTCCAGCAACTGCA>AY101347.................AGCAGTAGATTCTGTAATGTTCCAGCAACTGCA>AY101348.................AGCCGTAGATTCTGTAATGTTCCAGCAGCTGCA501550NC_001463(gag)AACAGTAGCAATGCAGCATGGCCTCGTGTCTGAGGACTTTGAAAGGCAGT>AY101347AACAGTAGCAATGCAGCATGGACTCGTGTATGAAGACTTTGAAAGGCTGT>AY101348AACAGTAGCAATGCAGCATGGCCTCGTGTCAGAGGACTTTGAAAGGCTTC551600NC_001463(gag)TGGCATATTATGCTACTACCTGGACAAGTAAAGACATACTAGAAGTATTG>AY101347CGGCATATTATGCTACTACCTGGACAAGTAAAGATATACTGGAAGTATTG>AY101348CAGCATATCATGCTACTACCTGGGCAAGTAAAGATATCTTAGAAGTACTG601650NC_001463(gag)GCCATGATGCCTGGAAATAGAGCTCAAAAGGAGTTAATTCAAGGGAAATT>AY101347GCCATGATGCCTGGGAATAGAGCTCAAAAAGAATTAATTCAAGGAAAATT>AY101348GCCATGATGCCTGGAAATAGAGCTCAAAAAGAGTTAATTCAAGGGAAATT651700NC_001463(gag)AAATGAAGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCTCCAGCAG>AY101347AAATGAAGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCTCAAGCAG>AY101348AAATGAAGAAGCAGAGAGGTGGAGAAGGAATAATCCACCACCTCCAGCAG701750NC_001463(gag)GAGGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAA>AY101347GCGGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAA>AY101348GAGGAGGGTTAACAGTGGATCAAATTATGGGAGTAGGACAAACAAATCAG751800NC_001463(gag)GCAGCAGCACAAGCTAACATGGATCAGGCAAGGCAAATATGCCTGCAATG>AY101347GCAGCTGCACAAGCTAACATGGATCAGGCAAGACAAATATGCCTGCAATG>AY101348GCAGCGGCACAAGCAAACATGGATCAGGCAAGACAAATATGCCTACAATG801850NC_001463(gag)GGTAATAAATGCATTAAGAGCAGTAAGACATATGGCGCACAGGCCAGGGA>AY101347GGTAATATCAGCCTTAAGAGCAGTGAGACATATGTCTCATAAACCAGGGA>AY101348GGTGATATCAGCACTAAGAGCAGTAAGGCATATGGCTCACAAGCCAGGGA851900NC_001463(gag)ATCCAATGCTAGTAAAGCAAAAAACGAATGAGCCATATGAAGATTTTGCA>AY101347ATCCGCTGCTAGTAAAGCAAAAAACAAATGAGTCATATGAAGATTTTGCA>AY101348ATCCAATGTTAGTAAAGCAAAAAGCAAATGAGCCATATGAAGAATTTGCA901950NC_001463(gag)GCAAGACTGCTAGAAGCAATAGATGCAGAGCCAGTTACACAGCCTATAAA>AY101347GCAAGACTGCTAGAAGCAATAGATGCAGAGCCAGTAGCACATCCTATAAA>AY101348GCAAGGCTGCTGGAAGCAATAGATGCCGAGCCAGTTAATCAGCCCATAAA9511000NC_001463(gag)AGATTATCTAAAGCTAACACTATCTTATACAAATGCATCAGCAGATTGTC>AY101347AGAATACTTAAAGTTAACACTATCTTATACGAATGCATCATCAGATTGTC>AY101348AGAATATCTAAAACTAACGTTGTCTTATACGAATGCATCCTCAGATTGTC10011050NC_001463(gag)AGAAGCAAATGGATAGAACACTAGGACAAAGAGTACAACAAGCTAGTGTA>AY101347AAAAGCAAATGGATAGAATGCTGGAATCAAGAGTACAACAAGCTAGTGTA>AY101348AGAAGCAAATGGATAGAACACTAGGACAAAGAGTCAAACAAGCTAGTGTA10511100NC_001463(gag)GAAGAAAAAATGCAAGCATGTAGAGATGTGGGATCAGAAGGGTTCAAAAT>AY101347GAACAAAAAA........................................>AY101348GAACAAAAAA........................................11011150NC_001463(gag)GCAATTGTTAGCACAAGCATTAAGGCCAGGAAAAGGAAAAGGGAATGGAC>AY101347..................................................>AY101348..................................................11511200NC_001463(gag)AGCCACAAAGGTGTTACAACTGTGGAAAACCGGGACATCAAGCAAGGCAA>AY101347..................................................>AY101348..................................................12011250NC_001463(gag)TGTAGACAAGGAATCATATGTCACAACTGTGGAAAGAGAGGACATATGCA>AY101347..................................................>AY101348..................................................12511300NC_001463(gag)AAAAGAATGCAGAGGAAAGAGAGACATAAGGGGAAAACAGCAGGGAAACG>AY101347..................................................>AY101348..................................................13011347NC_001463(gag)GGAGGAGGGGGATACGTGTGGTGCCGTCCGCTCCTCCTATGGAATAA>AY101347...............................................>AY101348...............................................表13PileUpMSF720TypeNCheck3690..NameNC_001463(gag720bp)(SEQIDNO53)Len720Check5792Weight0Name>L78446(SEQIDNO54)Len720Check272Weight0Name>L78447(SEQIDNO55)Len720Check1999Weight0Name>L78450(SEQIDNO56)Len720Check9633Weight0Name>L78451(SEQIDNO57)Len720Check5177Weight0Name>L78453(SEQIDNO58)Len720Check817Weight0//150NC_001463(gag720bp)ATGGTGAGTCTAGATAGAGACATGGCGAGGCAAGTCTCCGGGGGGAAAAG>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................51100NC_001463(gag720bp)AGATTATCCTGAGCTCGAAAAATGTATCAAGCATGCATGCAAGATAAAAG>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................101150NC_001463(gag720bp)TTCGACTCAGAGGGGAGCACTTGACAGAAGGAAATTGTTTATGGTGCCTT>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................151200NC_001463(gag720bp)AAAACATTAGATTACATGTTTGAGGACCATAAAGAGGAACCTTGGACAAA>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................201250NC_001463(gag720bp)AGTAAAATTTAGGACAATATGGCAGAAGGTGAAGAATCTAACTCCTGAGG>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................251300NC_001463(gag720bp)AGAGTAACAAAAAAGACTTTATGTCTTTGCAGGCCACATTAGCGGGTCTA>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................301350NC_001463(gag720bp)ATGTGTTGCCAAATGGGGATGAGACCTGAGACATTGCAAGATGCAATGGC>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................351400NC_001463(gag720bp)TACAGTAATCATGAAAGATGGGTTACTGGAACAAGAGGAAAAGAAGGAAG>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................401450NC_001463(gag720bp)ACAAAAGAGAAAAGGAAGAGAGTGTCTTCCCAATAGTAGTGCAAGCAGCA>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................451500NC_001463(gag720bp)GGAGGGAGAAGCTGGAAAGCAGTAGATTCTGTAATGTTCCAGCAACTGCA>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................501550NC_001463(gag720bp)AACAGTAGCAATGCAGCATGGCCTCGTGTCTGAGGACTTTGAAAGGCAGT>L78446.............CAGCATGGCCTCGTGTCCGAGGACTTTGAAAGGCAGT>L78447.............CAGCATGGAATAGTATCAGAAGAGTTTGAGAGGCAAC>L78450.............CAACATGGGATAGTATCAGAGGAATTTGAGAGACAAA>L78451.............CAGCATGGACTAGTATCAGAAGAATTTGAAAGGCAGC>L78453.............CAGCATGGACTTGTGTCCGAAGATTTTGAGAGGCAAT551600NC_001463(gag720bp)TGGCATATTATGCTACTACCTGGACAAGTAAAGACATACTAGAAGTATTG>L78446TGGCATATTATGCTACTACCTGGACAAGTAAGGACATATTAGAAGTATTG>L78447TGTCTTATTATGCTACCACTTGGACAAGCAAGGATATCTTAGAGGTACTA>L78450TGTCTTATTATGCTACCACATGGACAAGTAAGGATATTTTAGAAGTACTA>L78451TAGCATACTATGCCACAACGTGGACAAGCAAAGACATACTAGAGGTGTTA>L78453TGGCATATTATGCTACAACCTGGACTAGTGAAGATATATTAGAAGTATTG601650NC_001463(gag720bp)GCCATGATGCCTGGAAATAGAGCTCAAAAGGAGTTAATTCAAGGGADAAT>L78446GCCATGATGCCAGGAAATAGAGCTCAAAAGGAGCTAATTCAA........>L78447GCCATGATGCCTGGCAATAGAGCATTAAAAGAGCTAATACAA........>L78450GCAATGATGCCCGGGAACAGAGCATTAAAGGAGCTGATACAA........>L78451GCCATGATGCCAGGGAATAGAGCACAAAAAGAACTAATACAA........>L78453GCTATGATGCCTGGGAATAGAGCACAGAAAGAATTAATACAA........651700NC_001463(gag720bp)AAATGAAGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCTCCAGCAG>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................701720NC_001463(gag720bp)GAGGAGGATTAACAGTGGAT>L78446....................>L78447....................>L78450....................>L78451....................>L78453....................PileUpMSF1347TypeNCheck6947..NameNC_001463(gag)(SEQIDNO59)Len1347Check6959Weight0Name>L78446(SEQIDNO60)Len1347Check6690Weight0Name>L78447(SEQIDNO61)Len1347Check8417Weight0Name>L78450(SEQIDNO62)Len1347CheCk6051Weight0Name>L78451(SEQIDNO63)Len1347Check1595Weight0Name>L78453(SEQIDNO64)Len1347Check7235Weight0//150NC_001463(gag)ATGGTGAGTCTAGATAGAGACATGGCGAGGCAAGTCTCCGGGGGGAAAAG>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................51100NC_001463(gag)AGATTATCCTGAGCTCGAAAAATGTATCAAGCATGCATGCAAGATAAAAG>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................101150NC_001463(gag)TTCGACTCAGAGGGGAGCACTTGACAGAAGGAAATTGTTTATGGTGCCTT>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................151200NC_001463(gag)AAAACATTAGATTACATGTTTGAGGACCATAAAGAGGAACCTTGGACAAA>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................201250NC_001463(gag)AGTAAAATTTAGGACAATATGGCAGAAGGTGAAGAATCTAACTCCTGAGG>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................251300NC_001463(gag)AGAGTAACAAAAAAGACTTTATGTCTTTGCAGGCCACATTAGCGGGTCTA>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................301350NC_001463(gag)ATGTGTTGCCAAATGGGGATGAGACCTGAGACATTGCAAGATGCAATGGC>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................351400NC_001463(gag)TACAGTAATCATGAAAGATGGGTTACTGGAACAAGAGGAAAAGAAGGAAG>L78445..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................401450NC_001463(gag)ACAAAAGAGAAAAGGAAGAGAGTGTCTTCCCAATAGTAGTGCAAGCAGCA>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................451500NC_001463(gag)GGAGGGAGAAGCTGGAAAGCAGTAGATTCTGTAATGTTCCAGCAACTGCA>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................501550NC_001463(gag)AACAGTAGCAATGCAGCATGGCCTCGTGTCTGAGGACTTTGAAAGGCAGT>L78446.............CAGCATGGCCTCGTGTCCGAGGACTTTGAAAGGCAGT>L78447.............CAGCATGGAATAGTATCAGAAGAGTTTGAGAGGCAAC>L78450.............CAACATGGGATAGTATCAGAGGAATTTGAGAGACAAA>L78451.............CAGCATGGACTAGTATCAGAAGAATTTGAAAGGCAGC>L78453.............CAGCATGGACTTGTGTCCGAAGATTTTGAGAGGCAAT551600NC_001463(gag)TGGCATATTATGCTACTACCTGGACAAGTAAAGACATACTAGAAGTATTG>L78446TGGCATATTATGCTACTACCTGGACAAGTAAGGACATATTAGAAGTATTG>L78447TGTCTTATTATGCTACCACTTGGACAAGCAAGGATATCTTAGAGGTACTA>L78450TGTCTTATTATGCTACCACATGGACAAGTAAGGATATTTTAGAAGTACTA>L78451TAGCATACTATGCCACAACGTGGACAAGCAAAGACATACTAGAGGTGTTA>L78453TGGCATATTATGCTACAACCTGGACTAGTGAAGATATATTAGAAGTATTG601650NC_001463(gag)GCCATGATGCCTGGAAATAGAGCTCAAAAGGAGTTAATTCAAGGGAAATT>L78446GCCATGATGCCAGGAAATAGAGCTCAAAAGGAGCTAATTCAA........>L78447GCCATGATGCCTGGCAATAGAGCATTAAAAGAGCTAATACAA........>L78450GCAATGATGCCCGGGAACAGAGCATTAAAGGAGCTGATACAA........>L78451GCCATGATGCCAGGGAATAGAGCACAAAAAGAACTAATACAA........>L78453GCTATGATGCCTGGGAATAGAGCACAGAAAGAATTAATACAA........651700NC_001463(gag)AAATGAAGAAGCAGAAAGGTGGAGAAGGAATAATCCACCACCTCCAGCAG>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................701750NC_001463(gag)GAGGAGGATTAACAGTGGATCAAATTATGGGGGTAGGACAAACAAATCAA>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................751800NC_001463(gag)GCAGCAGCACAAGCTAACATGGATCAGGCAAGGCAAATATGCCTGCAATG>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................801850NC_001463(gag)GGTAATAAATGCATTAAGAGCAGTAAGACATATGGCGCACAGGCCAGGGA>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................851900NC_001463(gag)ATCCAATGCTAGTAAAGCAAAAAACGAATGAGCCATATGAAGATTTTGCA>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................901950NC_001463(gag)GCAAGACTGCTAGAAGCAATAGATGCAGAGCCAGTTACACAGCCTATAAA>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................9511000NC_001463(gag)AGATTATCTAAAGCTAACACTATCTTATACAAATGCATCAGCAGATTGTC>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................10011050NC_001463(gag)AGAAGCAAATGGATAGAACACTAGGACAAAGAGTACAACAAGCTAGTGTA>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................10511100NC_001463(gag)GAAGAAAAAATGCAAGCATGTAGAGATGTGGGATCAGAAGGGTTCAAAAT>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................11011150NC_001463(gag)GCAATTGTTAGCACAAGCATTAAGGCCAGGAAAAGGAAAAGGGAATGGAC>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................11511200NC_001463(gag)AGCCACAAAGGTGTTACAACTGTGGAAAACCGGGACATCAAGCAAGGCAA>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................12011250NC_001463(gag)TGTAGACAAGGAATCATATGTCACAACTGTGGAAAGAGAGGACATATGCA>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................12511300NC_001463(gag)AAAAGAATGCAGAGGAAAGAGAGACATAAGGGGAAAACAGCAGGGAAACG>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................13011347NC_001463(gag)GGAGGAGGGGGATACGTGTGGTGCCGTCCGCTCCTCCTATGGAATAA>L78446..................................................>L78447..................................................>L78450..................................................>L78451..................................................>L78453..................................................表14gag序列比对表NC_001463(gag720bp)vs.AF015181阳性41.0%一致性41.0%NC_001463(gag)vs.AF015181阳性40.6%一致性40.6%NC_001463(gag720bp)vs.AF402664~8阳性91.1%一致性32.2%NC_001463(gag)vs.AF402664~8阳性49.1%一致性35.0%NC_001463(gag720bp)vs.AJ305040~2阳性80.5%一致性38.1%NC_001463(gag)vs.AJ305040~2阳性44.3%一致性38.8%NC_01463(ga720bp)vs.AY047362阳性40.2%一致性40.2%NC_001463(gag)vs.AY047362阳性35.7%一致性35.7%NC_001463(gag720bp)vs.AY081139阳性40.0%一致性40.0%NC_001463(gag)vs.AY081139阳性39.8%一致性39.8%NC_001463(gag720bp)vs.AY101347~8阳性78.1%一致性35.0%NC_001463(gag)vs.AY101347~8阳性43.9%一致性37.9%NC_001463(gag720bp)vs.L78446,7,50,51,53阳性17.6%一致性11.9%NC_001463(gag)vs.L78446,47,50,51,53阳性9.4%一致性6.4%表15NC_001463(全基因组)vs.AF322109(全基因组)阳性68.2%一致性68.2%NC_001463(gag)vs.AF322109(gag)阳性73.1%一致性73.1%NC_001463(5’LTR区)vs.AF322109(5’LTR区)阳性59.8%一致性59.8%NC_001463(pol)vs.AF322109(pol)阳性74.9%一致性74.9%NC_001463(rev)vs.AF322109(rev)阳性48.3%一致性48.3%NC_001463(vif)vs.AF322109(vif)阳性66.0%一致性66.0%序列表<110>VECTORCOREACO.,LTD金连洙金钟必李修京<120>基于CAEV的载体系统<160>79<170>KopatentIn1.71<210>1<211>9189<212>DNA<213>羊关节炎-脑炎病毒<400>1gagttctaggagagtccctcctagtctctcctctccgaggaggtaccgagacctcaaaat60aaaggagtgattgccttactgccgagtggagagtgattactgagcggccggtgtatcggg120agtcgtcccttaatctgtgcaataccagagcggctctcgcagctggcgcccaacgtgggg180cccgaggagaagaaaagaaagcggccctgagaactcggcttctgaaaaagaggaagagga240caagttgctatagcaacaagagagaagaagtagagcaaaggtccagtggctcggaaaaag300aggaactgaaacttcggggacgcctgaaggagtaaggtaagtgactctgctgtacgcggg360gcgaggcagaggtttccttctaaattgaaagagaagtgttgctgcgagaggtcttggtgg420tcgagaatcctgtacaaaaaaaaggagggatctcggtcaggaccaggacccctgggagta480atacaacagcaacaccgtaagaaaatccgccatggtgagtctagatagagacatggcgag540gcaagtctccggggggaaaagagattatcctgagctcgaaaaatgtatcaagcatgcatg600caagataaaagttcgactcagaggggagcacttgacagaaggaaattgtttatggtgcct660taaaacattagattacatgtttgaggaccataaagaggaaccttggacaaaagtaaaatt720taggacaatatggcagaaggtgaagaatctaactcctgaggagagtaacaaaaaagactt780tatgtctttgcaggccacattagcgggtctaatgtgttgccaaatggggatgagacctga840gacattgcaagatgcaatggctacagtaatcatgaaagatgggttactggaacaagagga900aaagaaggaagacaaaagagaaaaggaagagagtgtcttcccaatagtagtgcaagcagc960aggagggagaagctggaaagcagtagattctgtaatgttccagcaactgcaaacagtagc1020aatgcagcatggcctcgtgtctgaggactttgaaaggcagttggcatattatgctactac1080ctggacaagtaaagacatactagaagtattggccatgatgcctggaaatagagctcaaaa1140ggagttaattcaagggaaattaaatgaagaagcagaaaggtggagaaggaataatccacc1200acctccagcaggaggaggattaacagtggatcaaattatgggggtaggacaaacaaatca1260agcagcagcacaagctaacatggatcaggcaaggcaaatatgcctgcaatgggtaataaa1320tgcattaagagcagtaagacatatggcgcacaggccagggaatccaatgctagtaaagca1380aaaaacgaatgagccatatgaagattttgcagcaagactgctagaagcaatagatgcaga1440gccagttacacagcctataaaagattatctaaagctaacactatcttatacaaatgcatc1500agcagattgtcagaagcaaatggatagaacactaggacaaagagtacaacaagctagtgt1560agaagaaaaaatgcaagcatgtagagatgtgggatcagaagggttcaaaatgcaattgtt1620agcacaagcattaaggccaggaaaaggaaaagggaatggacagccacaaaggtgttacaa1680ctgtggaaaaccgggacatcaagcaaggcaatgtagacaaggaatcatatgtcacaactg1740tggaaagagaggacatatgcaaaaagaatgcagaggaaagagagacataaggggaaaaca1800gcagggaaacgggaggagggggatacgtgtggtgccgtccgctcctcctatggaataact1860tcagcaccacctatggttcaggtccgcataggttcccagcagaggaacttgttatttgat1920accggggcggaccgaactatagttagatggcatgagggctcgggaaacccagccggaagg1980ataaaactgcaaggaataggaggaatagtagaaggagaaaaatggaataatgtagaatta2040gaatataaaggagaaacaagaaagggaacaatagtagtgttaccacaaagtccagtagaa2100gtattaggacgagataacatggcccgatttggaataaagataataatggcaaatttagag2160gaaaaaagaatcccaattacaaaagtaaaattgaaagagggatgtacgggtccacatgtc2220ccacaatggccattaacagaagagaaattaaaaggtctaacagaaatcatagataaatta2280gtggaagaaggaaaactaggaaaggcacccccacattggacatgtaatactccaatcttt2340tgcataaaaaagaaatcagggaagtggagaatgttaatagatttcagagaattgaacaaa2400cagacagaagatttaacagaagcgcagttaggactcccgcatccgggaggactacaaaag2460aaaaaacatgttacaatattggacataggagatgcatattttactatacccctatatgaa2520ccatatcgagagtacacatgttttactctattaagtcctaataatctaggaccatgtaaa2580agatactattggaaagtgctgccacaaggttggaaattgagtccatctgtatatcaattt2640actatgcaggagatcttagaggattggatacagcagcatccagaaattcaatttggcata2700tatatggatgatatttacataggaagtgatttagaaattaaaaagcatagagaaatagtg2760aaagatttagccaattatattgcccaatatggattcactctgccagaagagaagagacaa2820aagggatatccagcaaaatggctaggatttgaactacacccgcagacctggaaatttcag2880aagcatacattacctgaattaacaaagggaacaataacattaaataaattacagaaatta2940gtaggagaattagtatggagacaatccataattgggaaaagcattcctaacattctgaaa3000ttaatggaaggagatagagaattacaaagtgaaagaaaaattgaagaagtacatgtgaaa3060gaatgggaagcatgtaggaaaaaattagaagaaatggaaggaaattattataataaagac312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caaat840gagaactatgaagagtttgccgcaaggttgttagaagcagtggatgcagaacccgttacc900caacctataaaagaatatttaaaggtaactctgtcttacacaaatgcaaattcggaatgt960caaaaacatatggacagagtgttggggcaaagagtacagcaggcctcaatagaagaaaaa1020atgcaggcatgcagggacatcgggggaacagcatatcagatgcagttgcttgcacaagcc1080ctccgtggcggaaaagaagatgggaaaaaatctgtagggaagtgttataactgtggaagg1140cccggacacagagcaaaagaatgcagacaaggcattatatgtcacaactgtggaaaaaga1200gggcatatacagaaaaactgcaaacagaaaagaagaaaggagcagggaaacatgaggagg1260gggctacgtgtggtgccgtccgcaccccctatggagtaa1299<210>7<211>511<212>DNA<213>羊关节炎-脑炎病毒<400>7gagttctaggagagtccctcctagtctctcctctccgaggaggtaccgagacctcaaaat60aaaggagtgattgccttactgccgagtggagagtgattactgagcggccggtgtatcggg120agtcgtcccttaatctgtgcaataccagagcggctctcgcagctggcgcccaacgtgggg180cccgaggagaagaaaagaaagcggccctgagaactcggcttctgaaaaagaggaagagga240caagttgctatagcaacaagagagaagaagtagagcaaaggtccagtggctcggaaaaag300aggaactgaaacttcggggacgcctgaaggagtaaggtaagtgactctgctgtacgcggg360gcgaggcagaggtttccttctaaattgaaagagaagtgttgctgcgagaggtcttggtgg420tcgagaatcctgtacaaaaaaaaggagggatctcggtcaggaccaggacccctgggagta480atacaacagcaacaccgtaagaaaatccgcc511<210>8<211>576<212>DNA<213>羊关节炎-脑炎病毒<400>8gtgagtgctctgaggagctcgaaggaaagagtcctcagcctctcctctccgaggagcttc60ggctcataataaaggagtgcttgcttcaacagaactgagctggtcgtggttattatcggg120gaccgaagtcccgtgcaacaccggggcggttctcgcagctggcgcccaacgtggggctcg180agtagcttgagaagctcgactgagatctgaatccaagagcgacatcagacagcaagaaat240gagagtaatgagaccgcgagctctgctgctgtaaaaaagaggaagtagcgggttgccgag300gcaactgctcagaagaaccaggggaaagggcttccagcaacctcaaaagaggaaccgaga360cttcggggacgcctgaagtaaggtaagtgactctgctgtacgcggggcgaggcataggag420atccttctattctaggaagagaagcgctgttctgggaggtcttggcgaccgagaatcttg480ttaaataagccaggatctcgatcaggaccaagacccctcaggagagggtatagacagcgt540ggtaagaaatccgccgtggtgagtctagatagagac576<210>9<211>3318<212>DNA<213>羊关节炎-脑炎病毒<400>9atgtcacaactgtggaaagagaggacatatgcaaaaagaatgcagaggaaagagagacat60aaggggaaaacagcagggaaacgggaggagggggatacgtgtggtgccgtccgctcctcc120tatggaataacttcagcaccacctatggttcaggtccgcataggttcccagcagaggaac180ttgttatttgataccggggcggaccgaactatagttagatggcatgagggctcgggaaac240ccagccggaaggataaaactgcaaggaataggaggaatagtagaaggagaaaaatggaat300aatgtagaattagaatataaaggagaaacaagaaagggaacaatagtagtgttaccacaa360agtccagtagaagtattaggacgagataacatggcccgatttggaataaagataataatg420gcaaatttagaggaaaaaagaatcccaattacaaaagtaaaattgaaagagggatgtacg480ggtccacatgtcccacaatggccattaacagaagagaaattaaaaggtctaacagaaatc540atagataaattagtggaagaaggaaaactaggaaaggcacccccacattggacatgtaat600actccaatcttttgcataaaaaagaaatcagggaagtggagaatgttaatagatttcaga660gaattgaacaaacagacagaagatttaacagaagcgcagttaggactcccgcatccggga720ggactacaaaagaaaaaacatgttacaatattggacataggagatgcatattttactata780cccctatatgaaccatatcgagagtacacatgttttactctattaagtcctaataatcta840ggaccatgtaaaagatactattggaaagtgctgccacaaggttggaaattgagtccatct900gtatatcaatttactatgcaggagatcttagaggattggatacagcagcatccagaaatt960caatttggcatatatatggatgatatttacataggaagtgatttagaaattaaaaagcat1020agagaaatagtgaaagatttagccaattatattgcccaatatggattcactctgccagaa1080gagaagagacaaaagggatatccagcaaaatggctaggatttgaactacacccgcagacc1140tggaaatttcagaagcatacattacctgaattaacaaagggaacaataacattaaataaa1200ttacagaaattagtaggagaattagtatggagacaatccataattgggaaaagcattcct1260aacattctgaaattaatggaaggagatagagaattacaaagtgaaagaaaaattgaagaa1320gtacatgtgaaagaatgggaagcatgtaggaaaaaattagaagaaatggaaggaaattat1380tataataaagacaaagatgtctatggacaattggcttggggagacaaagctatagaatat1440atagtgtatcaggagaaagggaaaccattatgggtaaatgtggttcacaatataaagaac1500ctaagcatcccgcaacaggttattaaagcagcgcaaaaattaacccaagaagtcatcatt1560aggacaggaaaaataccatggatattgttgccagggaaagaagaagattggagactagaa1620ttgcaattagggaacatcacatggatgccaaaattttggtcctgttatcgaggacataca1680agatggagaaaaagaaatataatagaagaagtagtagaagggcctacatattatacagat1740ggaggaaaaaagaataaagtaggaagtctagggttcatagtatcaacaggggaaaaattt1800agaaagcatgaagagggcacaaaccagcaactagaattaagagccatagaggaagctcta1860aaacaagggcctcaaacaatgaatttagtaacagatagtagatatgcatttgaattttta1920ttaagaaattgggatgaagaagtaataaagaatccaattcaagcaagaattatggaaatt1980gcccacaagaaagataggataggagtgcattgggtgccaggacataaagggattccccaa2040aatgaagaaatagacaaatatatttcggaaatatttcttgcaaaagaaggagaaggaatt2100ctcccaaaaagagaagaggatgcagggtatgatttaatatgcccagaagaggttaccata2160gagccaggacaagtgaaatgcatccccatagagctaagattaaatttaaagaaatcacaa2220tgggctatgattgctacaaaaagcagcatggctgccaaaggagtgttcacacaaggagga2280atcatagactcaggatatcagggacaaatacaggtaataatgtataatagcaataaaata2340gcagtagtcataccccaagggagaaaatttgcacaattaatattaatggataaaaagcat2400ggaaaattggaaccctggggggaaagcagaaaaacagaaaggggagaaaaaggatttggg2460tctacaggaatgtattggatagaaaatattcctctggcagaggaagaccacacaaaatgg2520catcaagatgcccgatcattgcatctagaatttgaaattccaagaacagcagcagaagac2580atagtaaatcaatgtgaaatatgcaaagaagcgaggacacctgcagtaattagaggcgga2640aacaaaaggggggtaaatcattggcaagtggattatacccattatgaaaatatcatacta2700ttagtatgggtagaaacaaattcaggactaatatatgcagaaaaagtaaaaggagaatca2760gggcaagaattcagaataaaagtgatgcattggtatgcattatttggtccagagtcattg2820cagtcagacaatggacctgcatttgcagcagagcccacacagctgttaatgcaataccta2880ggagtaaaacacacaacaggcataccttggaatccacagtctcaggctatagtagaaagg2940gcacatcaactattgaaaagcactttaaagaagttccagccacaatttgtcgctgtagaa3000tcagccatagcagcagccctagtcgccataaatataaaaagaaagggtgggctggggaca3060agccctatggatatttttatatataataaagaacagaaaagaataaataataaatataat3120aaaaattctcaaaaaattcaattctgttattacagaataaggaaaagaggacatcaggag3180agtggaaaggaccaacccaggtactgtggaaaggggaaggagccaattgtggtaaaggat3240atagaaagtgaaaagtatttagtaataccttacaaagatgcaaaattcatcccgccacca3300acaaaagaaaaggaataa3318<210>10<211>3324<212>DNA<213>羊关节炎-脑炎病毒<400>10atgcagacaaggcattatatgtcacaactgtggaaaaagagggcatatacagaaaaactg60caaacagaaaagaagaaaggagcagggaaacatgaggagggggctacgtgtggtgccgtc120cgcaccccctatggagtaacgcaagcaccactaatagttagggtacaaatagggaatcag180gagaaacaattattatttgacacaggggcagataaaacgatagtaagaatgcatgatgga240acagggattccaaacggaagaataaaattacaagggataggaggaatagtagaaggagaa300aaatggaataaagtacccatgacatataagggagaaacatcctgcccaagcttggttgtg360ctaagagatagcccagtagaagtattgggaagagataacatggaagcattcggcgtaacc420ctaataatggcaaatttagaagataagaaaattcccacaataccagtagaattgaaagaa480ggatgtaaagggccacatgtgccccagtggccattaacagcagagaaattacaaggacta540acaggaatagtagaaaaattactacaggaaggaaaattggcagaggccccagagggatgg600acgtggaacacgcccatcttctgcataaaaaagaagtcaggaaaatggagaatgttaata660gattttagggaattaaataagcaaacagcagatttagcagaagcgcagctaggactgcca720cacccaggagggttgcaaaggaaaaagaatgtaacaattctggacataggagatgcatat780ttcacaattcccttatacgagccctatcagaaatatacatgcttcacactcctaagtcct840aacaatttgggaccatgtaaaaggtattattggaaagtattaccccagggatggaaattg900agcccagctgtatatcaattcaccatgcaaaggttgttaaaaggatggatacaacagcat960aaaaacatacaatttggaatatatatggatgatatctatattggaagtgatctaacgata1020gcccaacataggaagataatagaagaattagcctcatttatagaacaatttgggtttaca1080ttaccagaagataagagacaagagggctatccagcaaaatggctaggattcgagctacat1140ccagaaaaatggaaatatcaaaagcataaattgccggaattacaagagggggtaataacc1200ctgaacaaattacagaagatagtaggggaattagtgtggagacaatccttgataggaaag1260agcatccccaatatcataaaattaatggaaggagatcgcgcattacaaagtgaaaggaaa1320atagaaagaatacatgtacaagaatgggaagcatgtcaaaagaaattagatgaaatggta1380ggaaattattacagagaagaagaagatatctatggacaaataacttggggggataaggca1440ataaaatacatagtattccaaaggaaaggggaacccctatgggtaaatgtagtacatgac1500ataaaaaatttgagtctcccacagcaagtgataaaagcagcacagaaattaacccaggaa1560gtaatcataagaacaggaaaaatcccatggctgctactaccaggaagagaagaagactgg1620agattagaactgcaggtagggaacatcacgtggatgccatcattttggtcatgttatcga1680ggagcacccaagtggaaaagaaggaacatagtggcagcagtggtagatggaccgacatat1740tatacagatgggggaaagaaaaacgcacagggaagctttggcttcatctccccaacagga1800gaaaagttcagaaggcatgaagatggaactaatcaggtattagaattaagggcaatagaa1860gatccatgtaaacaaggacctgaaagcatgaacattgtaactgacagcaggtatgcttat1920gaattcatgctccgaaactgggatgaacaggtcataagaaaccccattcaggcaagaatc1980atggcagaagtgcacaagaaaaagcaggtaggaatacactgggtgccagggcataaagga2040atacctcagaatgaagagatagaccagtacatatcagaagtattcttagcacgagaagga2100acagggatatgtgaaaaaaggaaggaagatgctggatatgatttattatgcccgcatgag2160gtaatacttaaaccccaagaagtaaaacggatcccaatagacctaaaattaaaattgaaa2220gaaaagcaatgggccatgataagtgggaaaagtagcgttgcagcaaaaggaatatttgta2280caaggaggcataatagattcagggtatcagggacaagtacaagtcatcctatataatagt2340aataagatagaggtcaaaataccacaaggcaggaaatttgcccaattaatattaatgaac2400ttacaacatgaagaattagaagaatggggaaaggaaagaaaaacagaaagaggaacaaaa2460ggatttgggtctacaggagcattttggatagagaatattccccaagcagaggaagaacat2520tacaaatggcatcaagatgctagatctctgcagctagaattcaagatacctagagcagca2580gcagaagacattatacagcactgtgaggtatgtcaagaaggcaaacccgcagcgatcacg2640agagggggaaataaaagaggaatagatcattggcaggtagactatacacattacaaagaa2700cacataatattagtatgggtagagactaattcaggattaatatttgcagagaaagtaaaa2760ggagaatcaggacaagaatttaggatgcagacattgaaatggtatgctttgtttcaacca2820aaatcagtgcaatcagataatgggacagccttcacagctgaggctacgcagcatctaatg2880aagtatttagggattcagcacactacgggtattccgtggaacccccagtcacaaagttta2940gtagaaagagctcatcaaacattaaaacacatgttagaaaaattagaaccacaatttgtg3000gccctacagtctgccatcgcagccactctagttgcgctcaatataaaaagaaagggtgga3060ctaggggcaagccctatggatatttacatatataataaggagcaacaaagacaacaagat3120aatagtaataaattaattcagaaaaaattttgttattacaggatcagaaaaagaggccat3180ccaggagagtggaacggcccaactgaggtactgtgggaaggggaaggagccatagtagtt3240aaagacaaagaaagtgatagatatctagtcatcccatataaagatgcaaaatttattccg3300ccaccgtcggaacagaagggatag3324<210>11<211>402<212>DNA<213>羊关节炎-脑炎病毒<400>11atggatgctggggccagatacatgcgcttaactgggaaggaaaactgggttgaagtaacc60atggacggagagaaggaaaggaaaagagaaggtttcactgcgggacagcaagatatacag120aactctaagtaccccgacataccaacgggtcacagtcatcatggaaacaagagcagacgt180cgcaggagaaaatcaggattttggcgatggcttagaggaatcagacaacagcgaaacaag240cgaaagagtgacagtacagaaagcttggagccgtgcctgggagctttggcagaactcacc300ctggaaggagccatggaaaaggggcctgctgaggctgctcgtccttccgctgacgatggg360aatctggataaatggatggcttggagaacaccacaaaaataa402<210>12<211>321<212>DNA<213>羊关节炎-脑炎病毒<400>12atggcggagataagaaaagaagcaaaggagccactaatccaggaccaggtatcaacaagt60caacttggtgatggagacccgggtgcaactagaagaagaagaagaagaagacggaaggga120tggtggagatggctcagagagatgcagcgatcccgacaacaaaggaattatgaacgcctg180gaggagagcttgggtgacttggagaaactcaccttggcagaacacatggaagaatgtggt240ggtggcgccgttggtgattccgctgacaatcagaatttggctccttggagagaatggaga300gaacccctaaaagaaaaataa321<210>13<211>690<212>DNA<213>羊关节炎-脑炎病毒<400>13atgcaaaattcatcccgccaccaacaaaagaaaaggaataaaaaacctggaccagaatta60cccttagcactatggatacatatagcagaaagcattaatggggatagctcatggtacata120acaatgagactgcaacagatgatgtggggaaaaagaggaaataagttacaatataagaat180gaagacagggaatatgaaaattgggaaattacatcatggggatggaaaatgcacctaagg240agagtgaaacaatggatacaagacaacaggagaggaagcccatggcagtacaaagtagga300ggaacatggaaaagtataggagtgtggttcctgcaagcaggagattacagaaaggtagac360aggcacttctggtgggcatggaggatactgatatgttcctgcaggaaagaaaagtttgat420ataagagaatttatgagaggaagacatagatgggatttgtgcaaatcctgtgctcaagga480gaagtagtaaagcatactagaacaaaaagtctggaaagactagtactgctacagatggta540gaacagcatgtgtttcaagtattgccattgtggagagccaggagaagtagtacaacagat600ttcccatggtgcagggacacaacgggatacacgcatgcgtggtctgtccaggagtgctgg660ttgatggaatatctcttagaggatgagtga690<210>14<211>490<212>DNA<213>羊关节炎-脑炎病毒<400>14atgcaaaatttattccgccaccgtcggaacagaagggatagaagaataggcaaaaagtca60tccaagagggcatacttcgccatggcaatatcggagacaggatggatggaaggatgtggg120aacgtggttcctacagccaggggactatagaaaggcggatcagcagttctggttcgcttg180gagaatagtgtcgtgttcatgtaaaaaggaaggatttaacataagagaatttatgctagg240tacccatagatgggatttgtgtaagtcgtgttgccagggtgaagtagtaaagagaacaca300accctacaccttgcaaaggctcacgtggcttaaattaacagaagaccatgtatttcaagt360aatgcccttgtggagagctcgcaaagggattaccatagactttccctggtgcagggacac420aaaaggattcctggagccgtggacaacgcaagagtgttggcaaatagagtatcccttgga480ggatgagtga490<210>15<211>720<212>DNA<213>羊关节炎-脑炎病毒<400>15atggtgagtctagatagagacatggcgaggcaagtctccggggggaaaagagattatcct60gagctcgaaaaatgtatcaagcatgcatgcaagataaaagttcgactcagaggggagcac120ttgacagaaggaaattgtttatggtgccttaaaacattagattacatgtttgaggaccat180aaagaggaaccttggacaaaagtaaaatttaggacaatatggcagaaggtgaagaatcta240actcctgaggagagtaacaaaaaagactttatgtctttgcaggccacattagcgggtcta300atgtgttgccaaatggggatgagacctgagacattgcaagatgcaatggctacagtaatc360atgaaagatgggttactggaacaagaggaaaagaaggaagacaaaagagaaaaggaagag420agtgtcttcccaatagtagtgcaagcagcaggagggagaagctggaaagcagtagattct480gtaatgttccagcaactgcaaacagtagcaatgcagcatggcctcgtgtctgaggacttt540gaaaggcagttggcatattatgctactacctggacaagtaaagacatactagaagtattg600gccatgatgcctggaaatagagctcaaaaggagttaattcaagggaaattaaatgaagaa660gcagaaaggtggagaaggaataatccaccacctccagcaggaggaggattaacagtggat720720<210>16<211>591<212>DNA<213>羊关节炎-脑炎病毒<400>16gctgtagactctgtaatgttccaacaaatgcaaacagtagcaatgcagcatggcctcgtg60tccgaggattttgaaagacagttagcatattatgctactacctggacaagtaaagacata120ctagaagtattggccatgatgcctgggaatagggctcagaaagaacttattcaagggaaa180ttgaatgaagaagcagacaggtggagaaggaacaatccaccaggaggattaacagtggat240caaattatgggggtaggacaaacaaatcaagcagcagcacaagctaacatggatcaggca300agacaaatatgcctacaatgggtaataaacgccttaagagcagtaaggcatatggctcat360aggccagggaatccaatgctagtaaagcaaaaaacaaatgagccatatgaagaatttgca420gcaagactgctagaagcaatagatgcagaagcggttacacagcccataaaagagtatcta480aagctaacattatcctatacaaatgcagcctcagattgtcaaaagcaaatggagagagtg540ctaggacaaagagtacaacaggctagtgtagaaaaaaaaatgcaagcatgt591<210>17<211>1347<212>DNA<213>羊关节炎-脑炎病毒<400>17atggtgagtctagatagagacatggcgaggcaagtctccggggggaaaagagattatcct60gagctcgaaaaatgtatcaagcatgcatgcaagataaaagttcgactcagaggggagcac120ttgacagaaggaaattgtttatggtgccttaaaacattagattacatgtttgaggaccat180aaagaggaaccttggacaaaagtaaaatttaggacaatatggcagaaggtgaagaatcta240actcctgaggagagtaacaaaaaagactttatgtctttgcaggccacattagcgggtcta300atgtgttgccaaatggggatgagacctgagacattgcaagatgcaatggctacagtaatc360atgaaagatgggttactggaacaagaggaaaagaaggaagacaaaagagaaaaggaagag420agtgtcttcccaatagtagtgcaagcagcaggagggagaagctggaaagcagtagattct480gtaatgttccagcaactgcaaacagtagcaatgcagcatggcctcgtgtctgaggacttt540gaaaggcagttggcatattatgctactacctggacaagtaaagacatactagaagtattg600gccatgatgcctggaaatagagctcaaaaggagttaattcaagggaaattaaatgaagaa660gcagaaaggtggagaaggaataatccaccacctccagcaggaggaggattaacagtggat720caaattatgggggtaggacaaacaaatcaagcagcagcacaagctaacatggatcaggca780aggcaaatatgcctgcaatgggtaataaatgcattaagagcagtaagacatatggcgcac840aggccagggaatccaatgctagtaaagcaaaaaacgaatgagccatatgaagattttgca900gcaagactgctagaagcaatagatgcagagccagttacacagcctataaaagattatcta960aagctaacactatcttatacaaatgcatcagcagattgtcagaagcaaatggatagaaca1020ctaggacaaagagtacaacaagctagtgtagaagaaaaaatgcaagcatgtagagatgtg1080ggatcagaagggttcaaaatgcaattgttagcacaagcattaaggccaggaaaaggaaaa1140gggaatggacagccacaaaggtgttacaactgtggaaaaccgggacatcaagcaaggcaa1200tgtagacaaggaatcatatgtcacaactgtggaaagagaggacatatgcaaaaagaatgc1260agaggaaagagagacataaggggaaaacagcagggaaacgggaggagggggatacgtgtg1320gtgccgtccgctcctcctatggaataa1347<210>18<211>591<212>DNA<213>羊关节炎-脑炎病毒<400>18gctgtagactctgtaatgttccaacaaatgcaaacagtagcaatgcagcatggcctcgtg60tccgaggattttgaaagacagttagcatattatgctactacctggacaagtaaagacata120ctagaagtattggccatgatgcctgggaatagggctcagaaagaacttattcaagggaaa180ttgaatgaagaagcagacaggtggagaaggaacaatccaccaggaggattaacagtggat240caaattatgggggtaggacaaacaaatcaagcagcagcacaagctaacatggatcaggca300agacaaatatgcctacaatgggtaataaacgccttaagagcagtaaggcatatggctcat360aggccagggaatccaatgctagtaaagcaaaaaacaaatgagccatatgaagaatttgca420gcaagactgctagaagcaatagatgcagaagcggttacacagcccataaaagagtatcta480aagctaacattatcctatacaaatgcagcctcagattgtcaaaagcaaatggagagagtg540ctaggacaaagagtacaacaggctagtgtagaaaaaaaaatgcaagcatgt591<210>19<211>720<212>DNA<213>羊关节炎-脑炎病毒<400>19atggtgagtctagatagagacatggcgaggcaagtctccggggggaaaagagattatcct60gagctcgaaaaatgtatcaagcatgcatgcaagataaaagttcgactcagaggggagcac120ttgacagaaggaaattgtttatggtgccttaaaacattagattacatgtttgaggaccat180aaagaggaaccttggacaaaagtaaaatttaggacaatatggcagaaggtgaagaatcta240actcctgaggagagtaacaaaaaagactttatgtctttgcaggccacattagcgggtcta300atgtgttgccaaatggggatgagacctgagacattgcaagatgcaatggctacagtaatc360atgaaagatgggttactggaacaagaggaaaagaaggaagacaaaagagaaaaggaagag420agtgtcttcccaatagtagtgcaagcagcaggagggagaagctggaaagcagtagattct480gtaatgttccagcaactgcaaacagtagcaatgcagcatggcctcgtgtctgaggacttt540gaaaggcagttggcatattatgctactacctggacaagtaaagacatactagaagtattg600gccatgatgcctggaaatagagctcaaaaggagttaattcaagggaaattaaatgaagaa660gcagaaaggtggagaaggaataatccaccacctccagcaggaggaggattaacagtggat720720<210>20<211>662<212>DNA<213>羊关节炎-脑炎病毒<400>20tcaagcagcaggagggagaagctggaaagcagtagactcagtgatgttccagcaactgca60aaatgtagcaatgcagcatggcctcgtgtccgaggattttgaaaggcagttagtatatta120tgctactacctggacaagtaaagatatattagaagtattggccatgatgcctggaaatag180agctcaaaaagagttaattcaagggaaattgaatgaggaagcagaaaggtggagaagaaa240taatccaccacctcaagcaggcggaggattaacagtggatcaaattatgggggtaggaca300aacaaatcaagcagcggcacaggctaacatggatcaggcaagacaaatatgtctgcaatg360ggtaataacagcactaagagcagtgagacatatggctcacaaaccagggaatccaatgct420agtaaagcaaaaaacaaatgagtcatatgaagattttgccgcaagactgctagaagcaat480agatgcagaaccagttacacagcaaataaaagaatatttaaagttaacattatcttacac540aaatgcatcctcagactgtcagaaacagatggatagagtactaggacagagagtgcaaca600agctagtgtggaagaaaaaatgcaagcatgcagagatgtgggatcagaaggattcagaat660gc662<210>21<211>662<212>DNA<213>羊关节炎-脑炎病毒<400>21gcaagcagcaggagggagaagctggaaagcagtagactcagtgatgttccagcaactgca60aaatgtagcaatgcagcatggcctcgtgtccgaggattttgaaaggcagttagcatatta120tgctactacctggacaagtaaagatatattagaagtattggccatgatgcctggaaatag180agctcaaaaagagttaattcaagggaaattgaatgaggaagcagaaaggtggagaaggaa240taatccaccacctcaagcaggcggaggattaacagtggatcaaattatgggggtaggaca300aacaaatcaagcagcggcacaggctaacatggatcaggcaagacaaatatgcctgcaatg360ggtaataacagcactaagagcagtgagacatatggctcacaaaccagggaatccaatgct420agtaaagcaaaagacaaatgagtcatatgaagattttgccgcaagactgctagaagcaat480agatgcagaaccagttacacagcaaataaaagaatatttaaagttaacattatcttacac540aaatgcatcctcagactgtcaaaaacaaatggatagaatactaggacagagagtgcaaca600agctagtgtggaagaaaaaatgcaagcatgcagagatgtgggatcagaagggttcagaat660gc662<210>22<211>651<212>DNA<213>羊关节炎-脑炎病毒<400>22gcaagcagcaggagggagaagctggaaagcagtagactcagtgatgttccagcaactgca60aaatgtagcaatgcagcatggcctcgtgtccgaggattttgaaaggcagttggcatatta120tgctactacctggacaagtaaagatatattagaagtattggccatgatgcctggaaacag180agctcaaaaagagttaattcaggggaaattgaataaggaagcagaaaggtggagaaggaa240taatccaccacctcaagcacaaggaggattaacagtggatcaaattatgggggtaggaca300aacaaatcaggcagcggcacaggctaacatggatcaggcaagacaaatatgcctgcaatg360ggtaataacagcactaagagcagtgagacatatggctcacaaaccagggaatccaatgct420agtaaagcaaaagacaaatgagtcatatgaagattttgccgcaagactgctagaagcaat480agatgcagaaccagttacacagcaaataaaagaatatttaaagttaacattatcttacac540aaatgcatcctcagactgtcagaaacaaatggatagagtactaggacagagagtgcaaca600agctagtgtggaagaaaaaatgcaagcatgcagagatgtgggatcagaagg651<210>23<211>520<212>DNA<213>羊关节炎-脑炎病毒<400>23gcaagcagcaggagggagaagctggaaagcagtagactcagtgatgttccagcaactgca60aaatgtagcaatgcagcatggcctcgtgtccgaggattttgaaaggcagttagcatatta120tgctactacctggacaagtaaagatatattagaagtattggccatgatgcctggaaatag180agctcaaaaagagttaattcaagggaaattgaatgaggaagcagaaaggtggagaaggaa240taatccaccacctcaagcaggcggaggattaacagtggatcaaattatgggggtaggaca300aacaaatcaagcagcggcacaggctaacatggatcaggcaagacaaatatgcctgcaatg360ggtaataacagcactaagagcagtgagacatatggctcacaaaccagggaatccaatgct420agtaaagcaaaagacaaatgagtcatatgaagattttgccgcaagactgctagaagcaat480agatgcagaaccagttacacagcaaataaagaatatttaa520<210>24<211>663<212>DNA<213>羊关节炎-脑炎病毒<400>24gcaagcagcaggagggagaagctggaaagcagtagactcagtgatgttccagcaactgca60aaatgtagcaatgcagcatggcctcgtgtccgaggattttgaaaggcagttagcatatta120tgctactacctggacaagtaaagatatattagaagtattggccatgatgcctggaaatag180agctcaaaaagagttaattcaagggaaattgaatgaggaagcagaaaggtggagaaggaa240taatccaccacctcaagcaggcggaggattaacagtggatcaaattatgggggtaggaca300aacaaatcaagcagcggcacaggctaacatggatcaggcaagacaaatatgcctgcaatg360ggtaataacagcgactaagagcagtgagacatatggctcacaaaccagggaatccaatgc420tagtaaagcaaaagacaaatgagtcatatgaaaaattttcagcaagactcctagaagcaa480tagatgcagaaccagttacacagcctataaaagaatatttaaagttaacattatcttaca540caaatgcatcctcagactgtcaaaaacaaatggatagagtactaggacagagagtgcaac600aagctagtgtggaagaaaaaatgcaagcatgcagagatgtgggatcagaaggattcagaa660tgc663<210>25<211>1347<212>DNA<213>羊关节炎-脑炎病毒<400>25atggtgagtctagatagagacatggcgaggcaagtctccggggggaaaagagattatcct60gagctcgaaaaatgtatcaagcatgcatgcaagataaaagttcgactcagaggggagcac120ttgacagaaggaaattgtttatggtgccttaaaacattagattacatgtttgaggaccat180aaagaggaaccttggacaaaagtaaaatttaggacaatatggcagaaggtgaagaatcta240actcctgaggagagtaacaaaaaagactttatgtctttgcaggccacattagcgggtcta300atgtgttgccaaatggggatgagacctgagacattgcaagatgcaatggctacagtaatc360atgaaagatgggttactggaacaagaggaaaagaaggaagacaaaagagaaaaggaagag420agtgtcttcccaatagtagtgcaagcagcaggagggagaagctggaaagcagtagattct480gtaatgttccagcaactgcaaacagtagcaatgcagcatggcctcgtgtctgaggacttt540gaaaggcagttggcatattatgctactacctggacaagtaaagacatactagaagtattg600gccatgatgcctggaaatagagctcaaaaggagttaattcaagggaaattaaatgaagaa660gcagaaaggtggagaaggaataatccaccacctccagcaggaggaggattaacagtggat720caaattatgggggtaggacaaacaaatcaagcagcagcacaagctaacatggatcaggca780aggcaaatatgcctgcaatgggtaataaatgcattaagagcagtaagacatatggcgcac840aggccagggaatccaatgctagtaaagcaaaaaacgaatgagccatatgaagattttgca900gcaagactgctagaagcaatagatgcagagccagttacacagcctataaaagattatcta960aagctaacactatcttatacaaatgcatcagcagattgtcagaagcaaatggatagaaca1020ctaggacaaagagtacaacaagctagtgtagaagaaaaaatgcaagcatgtagagatgtg1080ggatcagaagggttcaaaatgcaattgttagcacaagcattaaggccaggaaaaggaaaa1140gggaatggacagccacaaaggtgttacaactgtggaaaaccgggacatcaagcaaggcaa1200tgtagacaaggaatcatatgtcacaactgtggaaagagaggacatatgcaaaaagaatgc1260agaggaaagagagacataaggggaaaacagcagggaaacgggaggagggggatacgtgtg1320gtgccgtccgctcctcctatggaataa1347<210>26<211>662<212>DNA<213>羊关节炎-脑炎病毒<400>26tcaagcagcaggagggagaagctggaaagcagtagactcagtgatgttccagcaactgca60aaatgtagcaatgcagcatggcctcgtgtccgaggattttgaaaggcagttagtatatta120tgctactacctggacaagtaaagatatattagaagtattggccatgatgcctggaaatag180agctcaaaaagagttaattcaagggaaattgaatgaggaagcagaaaggtggagaagaaa240taatccaccacctcaagcaggcggaggattaacagtggatcaaattatgggggtaggaca300aacaaatcaagcagcggcacaggctaacatggatcaggcaagacaaatatgtctgcaatg360ggtaataacagcactaagagcagtgagacatatggctcacaaaccagggaatccaatgct420agtaaagcaaaaaacaaatgagtcatatgaagattttgccgcaagactgctagaagcaat480agatgcagaaccagttacacagcaaataaaagaatatttaaagttaacattatcttacac540aaatgcatcctcagactgtcagaaacagatggatagagtactaggacagagagtgcaaca600agctagtgtggaagaaaaaatgcaagcatgcagagatgtgggatcagaaggattcagaat660gc662<210>27<211>662<212>DNA<213>羊关节炎-脑炎病毒<400>27gcaagcagcaggagggagaagctggaaagcagtagactcagtgatgttccagcaactgca60aaatgtagcaatgcagcatggcctcgtgtccgaggattttgaaaggcagttagcatatta120tgctactacctggacaagtaaagatatattagaagtattggccatgatgcctggaaatag180agctcaaaaagagttaattcaagggaaattgaatgaggaagcagaaaggtggagaaggaa240taatccaccacctcaagcaggcggaggattaacagtggatcaaattatgggggtaggaca300aacaaatcaagcagcggcacaggctaacatggatcaggcaagacaaatatgcctgcaatg360ggtaataacagcactaagagcagtgagacatatggctcacaaaccagggaatccaatgct420agtaaagcaaaagacaaatgagtcatatgaagattttgccgcaagactgctagaagcaat480agatgcagaaccagttacacagcaaataaaagaatatttaaagttaacattatcttacac540aaatgcatcctcagactgtcaaaaacaaatggatagaatactaggacagagagtgcaaca600agctagtgtggaagaaaaaatgcaagcatgcagagatgtgggatcagaagggttcagaat660gc662<210>28<211>651<212>DNA<213>羊关节炎-脑炎病毒<400>28gcaagcagcaggagggagaagctggaaagcagtagactcagtgatgttccagcaactgca60aaatgtagcaatgcagcatggcctcgtgtccgaggattttgaaaggcagttggcatatta120tgctactacctggacaagtaaagatatattagaagtattggccatgatgcctggaaacag180agctcaaaaagagttaattcaggggaaattgaataaggaagcagaaaggtggagaaggaa240taatccaccacctcaagcacaaggaggattaacagtggatcaaattatgggggtaggaca300aacaaatcaggcagcggcacaggctaacatggatcaggcaagacaaatatgcctgcaatg360ggtaataacagcactaagagcagtgagacatatggctcacaaaccagggaatccaatgct420agtaaagcaaaagacaaatgagtcatatgaagattttgccgcaagactgctagaagcaat480agatgcagaaccagttacacagcaaataaaagaatatttaaagttaacattatcttacac540aaatgcatcctcagactgtcagaaacaaatggatagagtactaggacagagagtgcaaca600agctagtgtggaagaaaaaatgcaagcatgcagagatgtgggatcagaagg651<210>29<211>520<212>DNA<213>羊关节炎-脑炎病毒<400>29gcaagcagcaggagggagaagctggaaagcagtagactcagtgatgttccagcaactgca60aaatgtagcaatgcagcatggcctcgtgtccgaggattttgaaaggcagttagcatatta120tgctactacctggacaagtaaagatatattagaagtattggccatgatgcctggaaatag180agctcaaaaagagttaattcaagggaaattgaatgaggaagcagaaaggtggagaaggaa240taatccaccacctcaagcaggcggaggattaacagtggatcaaattatgggggtaggaca300aacaaatcaagcagcggcacaggctaacatggatcaggcaagacaaatatgcctgcaatg360ggtaataacagcactaagagcagtgagacatatggctcacaaaccagggaatccaatgct420agtaaagcaaaagacaaatgagtcatatgaagattttgccgcaagactgctagaagcaat480agatgcagaaccagttacacagcaaataaagaatatttaa520<210>30<211>662<212>DNA<213>羊关节炎-脑炎病毒<400>30gcaagcagcaggagggagaagctggaaagcagtagactcagtgatgttccagcaactgca60aaatgtagcaatgcagcatggcctcgtgtccgaggattttgaaaggcagttagcatatta120tgctactacctggacaagtaaagatatattagaagtattggccatgatgcctggaaatag180agctcaaaaagagttaattcaagggaaattgaatgaggaagcagaaaggtggagaaggaa240taatccaccacctcaagcaggcggaggattaacagtggatcaaattatgggggtaggaca300aacaaatcaagcagcggcacaggctaacatggatcaggcaagacaaatatgcctgcaatg360ggtaataacagcactaagagcagtgagacatatggctcacaaaccagggaatccaatgct420agtaaagcaaaagacaaatgagtcatatgaaaaattttcagcaagactcctagaagcaat480agatgcagaaccagttacacagcctataaaagaatatttaaagttaacattatcttacac540aaatgcatcctcagactgtcaaaaacaaatggatagagtactaggacagagagtgcaaca600agctagtgtggaagaaaaaatgcaagcatgcagagatgtgggatcagaaggattcagaat660gc662<210>31<211>720<212>DNA<213>羊关节炎-脑炎病毒<400>31atggtgagtctagatagagacatggcgaggcaagtctccggggggaaaagagattatcct60gagctcgaaaaatgtatcaagcatgcatgcaagataaaagttcgactcagaggggagcac120ttgacagaaggaaattgtttatggtgccttaaaacattagattacatgtttgaggaccat180aaagaggaaccttggacaaaagtaaaatttaggacaatatggcagaaggtgaagaatcta240actcctgaggagagtaacaaaaaagactttatgtctttgcaggccacattagcgggtcta300atgtgttgccaaatggggatgagacctgagacattgcaagatgcaatggctacagtaatc360atgaaagatgggttactggaacaagaggaaaagaaggaagacaaaagagaaaaggaagag420agtgtcttcccaatagtagtgcaagcagcaggagggagaagctggaaagcagtagattct480gtaatgttccagcaactgcaaacagtagcaatgcagcatggcctcgtgtctgaggacttt540gaaaggcagttggcatattatgctactacctggacaagtaaagacatactagaagtattg600gccatgatgcctggaaatagagctcaaaaggagttaattcaagggaaattaaatgaagaa660gcagaaaggtggagaaggaataatccaccacctccagcaggaggaggattaacagtggat720720<210>32<211>597<212>DNA<213>羊关节炎-脑炎病毒<400>32gcagtcgatgctgtaatgttccagcaaatgcaaacagtagccatgcagcatggtcttgtg60tctgaggactttgaaaggcagttagcatattgtgctactacctggacaagtaaagatata120ttagaagtattggccatgatgcctggaaatagagctcaaaaagagttaattcaaggaaaa180ttaaacgaggaagcagaaaggtggagaaggaataatccaccgcctccacaaggaggggga240ttaacagtggatcaaattatggggataggacaaacaaatcaagcagcagcacaagctaac300atggatcaggcaagacacatatgcctgcaatgggtaataacagcattaagagcagtaaga360catatggctcacagaccagggaatccaatgctcgtaaaacaaaaaacaaatgagccatat420gaagagtttgcagcaaaactattagaagcaatagatgcagaaccagtaacacagcccata480aaagactatctaaagttaacattatcttatacaaatgcgtcctcagactgtcaaaagcaa540atggatagagtgctgggacaaagagtgcaacaagctagtgtagacgagaaaatgcaa597<210>33<211>597<212>DNA<213>羊关节炎-脑炎病毒<400>33gcagtagactcagtaatgttccagcaactgcaaacagtagcaatgcagcatggcctcgtg60tccgaggattttgaaaggcagttggcatattatgctactacctggacgagtaaagacata120ctagaagtattggccatgatgcctggaaacagagctcaaaaggagttaattcaagggaaa180ttaaatgaagaggcagaaaggtggagaagacataatccaccccctccggcgggaggagga240ttaacagtggatcaaattatgggggtaggacaaacaaatcaagcagcagcacaagctaac300atggatcaggcaagacaaatatgcctgcaatgggtaataacagcattaagagcagtgagg360tatatgactcacaaaccagggaatccaatgctagtaaaacaaaaaacaaatgaagcatat420gaagagtttacagcgagactgctagaagcaatagatgcagagccagtaacacagcccaca480aaagaatatctaaaactaacattatcttatacaaatgcatcctcagactgtcaaaagcaa540atggatagagtactaggacaaagagtgcaacaagctagtgtagaagaaaaaatgcaa597<210>34<211>597<212>DNA<213>羊关节炎-脑炎病毒<400>34gcagtcgatgctgtaatgttccagcaaatgcaaacagtagccatgcagcatggtcttgtg60tctgaggactttgaaaggcagttagcatattatgctactacctggacaagtaaagatata120ttagaagtattggccatgatgcctggaaatagagctcaaaaagagttaattcaaggaaaa180ttaaatgaggaagcagaaaggtggagaaggaataatccaccgcctccacagggaggggga240ttaacagtggatcaaattatggggataggacaaacaaatcaagcagcagcacaagctaac300atggatcaggcaagacacatatgcctgcaatgggtaataacagcattaagagcagtaaga360catatggctcacagaccagggaatccaatgctcgtaaaacaaaaaacaaatgagccatat420gaagagtttgcagcaaaactattagaagcaatagatgcagaaccagtaacacagctcata480aaagactatctaaagttaacattatcttatacaaatgcgtcctcagactgtcaaaagcaa540atggatagagtgctgggacaaagagtgcaacaagctagtgtagacgagaagatgcaa597<210>35<211>1347<212>DNA<213>羊关节炎-脑炎病毒<400>35atggtgagtctagatagagacatggcgaggcaagtctccggggggaaaagagattatcct60gagctcgaaaaatgtatcaagcatgcatgcaagataaaagttcgactcagaggggagcac120ttgacagaaggaaattgtttatggtgccttaaaacattagattacatgtttgaggaccat180aaagaggaaccttggacaaaagtaaaatttaggacaatatggcagaaggtgaagaatcta240actcctgaggagagtaacaaaaaagactttatgtctttgcaggccacattagcgggtcta300atgtgttgccaaatggggatgagacctgagacattgcaagatgcaatggctacagtaatc360atgaaagatgggttactggaacaagaggaaaagaaggaagacaaaagagaaaaggaagag420agtgtcttcccaatagtagtgcaagcagcaggagggagaagctggaaagcagtagattct480gtaatgttccagcaactgcaaacagtagcaatgcagcatggcctcgtgtctgaggacttt540gaaaggcagttggcatattatgctactacctggacaagtaaagacatactagaagtattg600gccatgatgcctggaaatagagctcaaaaggagttaattcaagggaaattaaatgaagaa660gcagaaaggtggagaaggaataatccaccacctccagcaggaggaggattaacagtggat720caaattatgggggtaggacaaacaaatcaagcagcagcacaagctaacatggatcaggca780aggcaaatatgcctgcaatgggtaataaatgcattaagagcagtaagacatatggcgcac840aggccagggaatccaatgctagtaaagcaaaaaacgaatgagccatatgaagattttgca900gcaagactgctagaagcaatagatgcagagccagttacacagcctataaaagattatcta960aagctaacactatcttatacaaatgcatcagcagattgtcagaagcaaatggatagaaca1020ctaggacaaagagtacaacaagctagtgtagaagaaaaaatgcaagcatgtagagatgtg1080ggatcagaagggttcaaaatgcaattgttagcacaagcattaaggccaggaaaaggaaaa1140gggaatggacagccacaaaggtgttacaactgtggaaaaccgggacatcaagcaaggcaa1200tgtagacaaggaatcatatgtcacaactgtggaaagagaggacatatgcaaaaagaatgc1260agaggaaagagagacataaggggaaaacagcagggaaacgggaggagggggatacgtgtg1320gtgccgtccgctcctcctatggaataa1347<210>36<211>597<212>DNA<213>羊关节炎-脑炎病毒<400>36gcagtcgatgctgtaatgttccagcaaatgcaaacagtagccatgcagcatggtcttgtg60tctgaggactttgaaaggcagttagcatattgtgctactacctggacaagtaaagatata120ttagaagtattggccatgatgcctggaaatagagctcaaaaagagttaattcaaggaaaa180ttaaacgaggaagcagaaaggtggagaaggaataatccaccgcctccacaaggaggggga240ttaacagtggatcaaattatggggataggacaaacaaatcaagcagcagcacaagctaac300atggatcaggcaagacacatatgcctgcaatgggtaataacagcattaagagcagtaaga360catatggctcacagaccagggaatccaatgctcgtaaaacaaaaaacaaatgagccatat420gaagagtttgcagcaaaactattagaagcaatagatgcagaaccagtaacacagcccata480aaagactatctaaagttaacattatcttatacaaatgcgtcctcagactgtcaaaagcaa540atggatagagtgctgggacaaagagtgcaacaagctagtgtagacgagaaaatgcaa597<210>37<211>597<212>DNA<213>羊关节炎-脑炎病毒<400>37gcagtagactcagtaatgttccagcaactgcaaacagtagcaatgcagcatggcctcgtg60tccgaggattttgaaaggcagttggcatattatgctactacctggacgagtaaagacata120ctagaagtattggccatgatgcctggaaacagagctcaaaaggagttaattcaagggaaa180ttaaatgaagaggcagaaaggtggagaagacataatccaccccctccggcgggaggagga240ttaacagtggatcaaattatgggggtaggacaaacaaatcaagcagcagcacaagctaac300atggatcaggcaagacaaatatgcctgcaatgggtaataacagcattaagagcagtgagg360tatatgactcacaaaccagggaatccaatgctagtaaaacaaaaaacaaatgaagcatat420gaagagtttacagcgagactgctagaagcaatagatgcagagccagtaacacagcccaca480aaagaatatctaaaactaacattatcttatacaaatgcatcctcagactgtcaaaagcaa540atggatagagtactaggacaaagagtgcaacaagctagtgtagaagaaaaaatgcaa597<210>38<211>597<212>DNA<213>羊关节炎-脑炎病毒<400>38gcagtcgatgctgtaatgttccagcaaatgcaaacagtagccatgcagcatggtcttgtg60tctgaggactttgaaaggcagttagcatattatgctactacctggacaagtaaagatata120ttagaagtattggccatgatgcctggaaatagagctcaaaaagagttaattcaaggaaaa180ttaaatgaggaagcagaaaggtggagaaggaataatccaccgcctccacagggaggggga240ttaacagtggatcaaattatggggataggacaaacaaatcaagcagcagcacaagctaac300atggatcaggcaagacacatatgcctgcaatgggtaataacagcattaagagcagtaaga360catatggctcacagaccagggaatccaatgctcgtaaaacaaaaaacaaatgagccatat420gaagagtttgcagcaaaactattagaagcaatagatgcagaaccagtaacacagctcata480aaagactatctaaagttaacattatcttatacaaatgcgtcctcagactgtcaaaagcaa540atggatagagtgctgggacaaagagtgcaacaagctagtgtagacgagaagatgcaa597<210>39<211>720<212>DNA<213>羊关节炎-脑炎病毒<400>39atggtgagtctagatagagacatggcgaggcaagtctccggggggaaaagagattatcct60gagctcgaaaaatgtatcaagcatgcatgcaagataaaagttcgactcagaggggagcac120ttgacagaaggaaattgtttatggtgccttaaaacattagattacatgtttgaggaccat180aaagaggaaccttggacaaaagtaaaatttaggacaatatggcagaaggtgaagaatcta240actcctgaggagagtaacaaaaaagactttatgtctttgcaggccacattagcgggtcta300atgtgttgccaaatggggatgagacctgagacattgcaagatgcaatggctacagtaatc360atgaaagatgggttactggaacaagaggaaaagaaggaagacaaaagagaaaaggaagag420agtgtcttcccaatagtagtgcaagcagcaggagggagaagctggaaagcagtagattct480gtaatgttccagcaactgcaaacagtagcaatgcagcatggcctcgtgtctgaggacttt540gaaaggcagttggcatattatgctactacctggacaagtaaagacatactagaagtattg600gccatgatgcctggaaatagagctcaaaaggagttaattcaagggaaattaaatgaagaa660gcagaaaggtggagaaggaataatccaccacctccagcaggaggaggattaacagtggat720720<210>40<211>524<212>DNA<213>羊关节炎-脑炎病毒<400>40taaagatatattagaagtattggccatgatgcctggaaatagagctcaaaaagagttaat60tcaagggaaattgaatgaagaagcagaaaggtggagaaggaataatccaccacctcaagc120aggcggaggattaacagtggatcaaattatgggggtaggacaaacaaatcaagcagcggc180acaggctaacatggatcaggcaagacaaatatgcctgcaatgggtaataacagcactaag240agcagtgagacatatggctcacaaaccagggaatccgatgctagtaaagcaaaaaacaaa300tgagtcatatgaagattttgccgcaagactgctagaagcaatagatgcagaaccagttac360aaagcaaataaaagaatatttaaagttaacattatcttacacaaatgcatcctcagactg420taagaaacagatggatagagtactaggacagagagtgcaacaagctagtgtggaagaaaa480aatgcaagcatgcagagatgtgggatcagaaggattcagaatgc524<210>41<211>1347<212>DNA<213>羊关节炎-脑炎病毒<400>41atggtgagtctagatagagacatggcgaggcaagtctccggggggaaaagagattatcct60gagctcgaaaaatgtatcaagcatgcatgcaagataaaagttcgactcagaggggagcac120ttgacagaaggaaattgtttatggtgccttaaaacattagattacatgtttgaggaccat180aaagaggaaccttggacaaaagtaaaatttaggacaatatggcagaaggtgaagaatcta240actcctgaggagagtaacaaaaaagactttatgtctttgcaggccacattagcgggtcta300atgtgttgccaaatggggatgagacctgagacattgcaagatgcaatggctacagtaatc360atgaaagatgggttactggaacaagaggaaaagaaggaagacaaaagagaaaaggaagag420agtgtcttcccaatagtagtgcaagcagcaggagggagaagctggaaagcagtagattct480gtaatgttccagcaactgcaaacagtagcaatgcagcatggcctcgtgtctgaggacttt540gaaaggcagttggcatattatgctactacctggacaagtaaagacatactagaagtattg600gccatgatgcctggaaatagagctcaaaaggagttaattcaagggaaattaaatgaagaa660gcagaaaggtggagaaggaataatccaccacctccagcaggaggaggattaacagtggat720caaattatgggggtaggacaaacaaatcaagcagcagcacaagctaacatggatcaggca780aggcaaatatgcctgcaatgggtaataaatgcattaagagcagtaagacatatggcgcac840aggccagggaatccaatgctagtaaagcaaaaaacgaatgagccatatgaagattttgca900gcaagactgctagaagcaatagatgcagagccagttacacagcctataaaagattatcta960aagctaacactatcttatacaaatgcatcagcagattgtcagaagcaaatggatagaaca1020ctaggacaaagagtacaacaagctagtgtagaagaaaaaatgcaagcatgtagagatgtg1080ggatcagaagggttcaaaatgcaattgttagcacaagcattaaggccaggaaaaggaaaa1140gggaatggacagccacaaaggtgttacaactgtggaaaaccgggacatcaagcaaggcaa1200tgtagacaaggaatcatatgtcacaactgtggaaagagaggacatatgcaaaaagaatgc1260agaggaaagagagacataaggggaaaacagcagggaaacgggaggagggggatacgtgtg1320gtgccgtccgctcctcctatggaataa1347<210>42<211>524<212>DNA<213>羊关节炎-脑炎病毒<400>42taaagatatattagaagtattggccatgatgcctggaaatagagctcaaaaagagttaat60tcaagggaaattgaatgaagaagcagaaaggtggagaaggaataatccaccacctcaagc120aggcggaggattaacagtggatcaaattatgggggtaggacaaacaaatcaagcagcggc180acaggctaacatggatcaggcaagacaaatatgcctgcaatgggtaataacagcactaag240agcagtgagacatatggctcacaaaccagggaatccgatgctagtaaagcaaaaaacaaa300tgagtcatatgaagattttgccgcaagactgctagaagcaatagatgcagaaccagttac360aaagcaaataaaagaatatttaaagttaacattatcttacacaaatgcatcctcagactg420taagaaacagatggatagagtactaggacagagagtgcaacaagctagtgtggaagaaaa480aatgcaagcatgcagagatgtgggatcagaaggattcagaatgc524<210>43<211>720<212>DNA<213>羊关节炎-脑炎病毒<400>43atggtgagtctagatagagacatggcgaggcaagtctccggggggaaaagagattatcct60gagctcgaaaaatgtatcaagcatgcatgcaagataaaagttcgactcagaggggagcac120ttgacagaaggaaattgtttatggtgccttaaaacattagattacatgtttgaggaccat180aaagaggaaccttggacaaaagtaaaatttaggacaatatggcagaaggtgaagaatcta240actcctgaggagagtaacaaaaaagactttatgtctttgcaggccacattagcgggtcta300atgtgttgccaaatggggatgagacctgagacattgcaagatgcaatggctacagtaatc360atgaaagatgggttactggaacaagaggaaaagaaggaagacaaaagagaaaaggaagag420agtgtcttcccaatagtagtgcaagcagcaggagggagaagctggaaagcagtagattct480gtaatgttccagcaactgcaaacagtagcaatgcagcatggcctcgtgtctgaggacttt540gaaaggcagttggcatattatgctactacctggacaagtaaagacatactagaagtattg600gccatgatgcctggaaatagagctcaaaaggagttaattcaagggaaattaaatgaagaa660gcagaaaggtggagaaggaataatccaccacctccagcaggaggaggattaacagtggat720720<210>44<211>593<212>DNA<213>羊关节炎-脑炎病毒<400>44tgccgtagactctgtgatgttccaccagctgcatacagtagcaatgccgcatggcctcgt60gtctgaggactttgaaaggcagttggcatattatgctactacctggacaagtaaagatat120actggaagtattggccatgatgcctgggaatagagctcaaaaagaattaattcaaggaaa180attaaatgaagaagcagaaaggtggagaaggaataatccaccacctcaagcaggcggagg240attaacagtggatcaaattatgggggtaggacaaacaaatcaagcagctgcacaagctaa300catggatcaggcaagacaaatatgcctgcaatgggtaatatcagccttaagagcagtgag360acatatgtctcataaaccagggaatccgctgctagtaaagcaaaaaacaaatgagtcata420tgaagattttgcagctagactgctagaagcaatagatccagccccagtagcacatcctat480aaaagattatttaaagttaacactatcttatacgaatgcatcatcagattgtcaaaagca540aatgggtagaatgctaggatcgagagtccatcaagccagtgtgggccaaaaaa593<210>45<211>1347<212>DNA<213>羊关节炎-脑炎病毒<400>45atggtgagtctagatagagacatggcgaggcaagtctccggggggaaaagagattatcct60gagctcgaaaaatgtatcaagcatgcatgcaagataaaagttcgactcagaggggagcac120ttgacagaaggaaattgtttatggtgccttaaaacattagattacatgtttgaggaccat180aaagaggaaccttggacaaaagtaaaatttaggacaatatggcagaaggtgaagaatcta240actcctgaggagagtaacaaaaaagactttatgtctttgcaggccacattagcgggtcta300atgtgttgccaaatggggatgagacctgagacattgcaagatgcaatggctacagtaatc360atgaaagatgggttactggaacaagaggaaaagaaggaagacaaaagagaaaaggaagag420agtgtcttcccaatagtagtgcaagcagcaggagggagaagctggaaagcagtagattct480gtaatgttccagcaactgcaaacagtagcaatgcagcatggcctcgtgtctgaggacttt540gaaaggcagttggcatattatgctactacctggacaagtaaagacatactagaagtattg600gccatgatgcctggaaatagagctcaaaaggagttaattcaagggaaattaaatgaagaa660gcagaaaggtggagaaggaataatccaccacctccagcaggaggaggattaacagtggat720caaattatgggggtaggacaaacaaatcaagcagcagcacaagctaacatggatcaggca780aggcaaatatgcctgcaatgggtaataaatgcattaagagcagtaagacatatggcgcac840aggccagggaatccaatgctagtaaagcaaaaaacgaatgagccatatgaagattttgca900gcaagactgctagaagcaatagatgcagagccagttacacagcctataaaagattatcta960aagctaacactatcttatacaaatgcatcagcagattgtcagaagcaaatggatagaaca1020ctaggacaaagagtacaacaagctagtgtagaagaaaaaatgcaagcatgtagagatgtg1080ggatcagaagggttcaaaatgcaattgttagcacaagcattaaggccaggaaaaggaaaa1140gggaatggacagccacaaaggtgttacaactgtggaaaaccgggacatcaagcaaggcaa1200tgtagacaaggaatcatatgtcacaactgtggaaagagaggacatatgcaaaaagaatgc1260agaggaaagagagacataaggggaaaacagcagggaaacgggaggagggggatacgtgtg1320gtgccgtccgctcctcctatggaataa1347<210>46<211>593<212>DNA<213>羊关节炎-脑炎病毒<400>46tgccgtagactctgtgatgttccaccagctgcatacagtagcaatgccgcatggcctcgt60gtctgaggactttgaaaggcagttggcatattatgctactacctggacaagtaaagatat120actggaagtattggccatgatgcctgggaatagagctcaaaaagaattaattcaaggaaa180attaaatgaagaagcagaaaggtggagaaggaataatccaccacctcaagcaggcggagg240attaacagtggatcaaattatgggggtaggacaaacaaatcaagcagctgcacaagctaa300catggatcaggcaagacaaatatgcctgcaatgggtaatatcagccttaagagcagtgag360acatatgtctcataaaccagggaatccgctgctagtaaagcaaaaaacaaatgagtcata420tgaagattttgcagctagactgctagaagcaatagatccagccccagtagcacatcctat480aaaagattatttaaagttaacactatcttatacgaatgcatcatcagattgtcaaaagca540aatgggtagaatgctaggatcgagagtccatcaagccagtgtgggccaaaaaa593<210>47<211>720<212>DNA<213>羊关节炎-脑炎病毒<400>47atggtgagtctagatagagacatggcgaggcaagtctccggggggaaaagagattatcct60gagctcgaaaaatgtatcaagcatgcatgcaagataaaagttcgactcagaggggagcac120ttgacagaaggaaattgtttatggtgccttaaaacattagattacatgtttgaggaccat180aaagaggaaccttggacaaaagtaaaatttaggacaatatggcagaaggtgaagaatcta240actcctgaggagagtaacaaaaaagactttatgtctttgcaggccacattagcgggtcta300atgtgttgccaaatggggatgagacctgagacattgcaagatgcaatggctacagtaatc360atgaaagatgggttactggaacaagaggaaaagaaggaagacaaaagagaaaaggaagag420agtgtcttcccaatagtagtgcaagcagcaggagggagaagctggaaagcagtagattct480gtaatgttccagcaactgcaaacagtagcaatgcagcatggcctcgtgtctgaggacttt540gaaaggcagttggcatattatgctactacctggacaagtaaagacatactagaagtattg600gccatgatgcctggaaatagagctcaaaaggagttaattcaagggaaattaaatgaagaa660gcagaaaggtggagaaggaataatccaccacctccagcaggaggaggattaacagtggat720720<210>48<211>593<212>DNA<213>羊关节炎-脑炎病毒<400>48agcagtagattctgtaatgttccagcaactgcaaacagtagcaatgcagcatggactcgt60gtatgaagactttgaaaggctgtcggcatattatgctactacctggacaagtaaagatat120actggaagtattggccatgatgcctgggaatagagctcaaaaagaattaattcaaggaaa180attaaatgaagaagcagaaaggtggagaaggaataatccaccacctcaagcaggcggagg240attaacagtggatcaaattatgggggtaggacaaacaaatcaagcagctgcacaagctaa300catggatcaggcaagacaaatatgcctgcaatgggtaatatcagccttaagagcagtgag360acatatgtctcataaaccagggaatccgctgctagtaaagcaaaaaacaaatgagtcata420tgaagattttgcagcaagactgctagaagcaatagatgcagagccagtagcacatcctat480aaaagaatacttaaagttaacactatcttatacgaatgcatcatcagattgtcaaaagca540aatggatagaatgctggaatcaagagtacaacaagctagtgtagaacaaaaaa593<210>49<211>593<212>DNA<213>羊关节炎-脑炎病毒<400>49agccgtagattctgtaatgttccagcagctgcaaacagtagcaatgcagcatggcctcgt60gtcagaggactttgaaaggcttccagcatatcatgctactacctgggcaagtaaagatat120cttagaagtactggccatgatgcctggaaatagagctcaaaaagagttaattcaagggaa180attaaatgaagaagcagagaggtggagaaggaataatccaccacctccagcaggaggagg240gttaacagtggatcaaattatgggagtaggacaaacaaatcaggcagcggcacaagcaaa300catggatcaggcaagacaaatatgcctacaatgggtgatatcagcactaagagcagtaag360gcatatggctcacaagccagggaatccaatgttagtaaagcaaaaagcaaatgagccata420tgaagaatttgcagcaaggctgctggaagcaatagatgccgagccagttaatcagcccat480aaaagaatatctaaaactaacgttgtcttatacgaatgcatcctcagattgtcagaagca540aatggatagaacactaggacaaagagtcaaacaagctagtgtagaacaaaaaa593<210>50<211>1347<212>DNA<213>羊关节炎-脑炎病毒<400>50atggtgagtctagatagagacatggcgaggcaagtctccggggggaaaagagattatcct60gagctcgaaaaatgtatcaagcatgcatgcaagataaaagttcgactcagaggggagcac120ttgacagaaggaaattgtttatggtgccttaaaacattagattacatgtttgaggaccat180aaagaggaaccttggacaaaagtaaaatttaggacaatatggcagaaggtgaagaatcta240actcctgaggagagtaacaaaaaagactttatgtctttgcaggccacattagcgggtcta300atgtgttgccaaatggggatgagacctgagacattgcaagatgcaatggctacagtaatc360atgaaagatgggttactggaacaagaggaaaagaaggaagacaaaagagaaaaggaagag420agtgtcttcccaatagtagtgcaagcagcaggagggagaagctggaaagcagtagattct480gtaatgttccagcaactgcaaacagtagcaatgcagcatggcctcgtgtctgaggacttt540gaaaggcagttggcatattatgctactacctggacaagtaaagacatactagaagtattg600gccatgatgcctggaaatagagctcaaaaggagttaattcaagggaaattaaatgaagaa660gcagaaaggtggagaaggaataatccaccacctccagcaggaggaggattaacagtggat720caaattatgggggtaggacaaacaaatcaagcagcagcacaagctaacatggatcaggca780aggcaaatatgcctgcaatgggtaataaatgcattaagagcagtaagacatatggcgcac840aggccagggaatccaatgctagtaaagcaaaaaacgaatgagccatatgaagattttgca900gcaagactgctagaagcaatagatgcagagccagttacacagcctataaaagattatcta960aagctaacactatcttatacaaatgcatcagcagattgtcagaagcaaatggatagaaca1020ctaggacaaagagtacaacaagctagtgtagaagaaaaaatgcaagcatgtagagatgtg1080ggatcagaagggttcaaaatgcaattgttagcacaagcattaaggccaggaaaaggaaaa1140gggaatggacagccacaaaggtgttacaactgtggaaaaccgggacatcaagcaaggcaa1200tgtagacaaggaatcatatgtcacaactgtggaaagagaggacatatgcaaaaagaatgc1260agaggaaagagagacataaggggaaaacagcagggaaacgggaggagggggatacgtgtg1320gtgccgtccgctcctcctatggaataa1347<210>51<211>593<212>DNA<213>羊关节炎-脑炎病毒<400>51agcagtagattctgtaatgttccagcaactgcaaacagtagcaatgcagcatggactcgt60gtatgaagactttgaaaggctgtcggcatattatgctactacctggacaagtaaagatat120actggaagtattggccatgatgcctgggaatagagctcaaaaagaattaattcaaggaaa180attaaatgaagaagcagaaaggtggagaaggaataatccaccacctcaagcaggcggagg240attaacagtggatcaaattatgggggtaggacaaacaaatcaagcagctgcacaagctaa300catggatcaggcaagacaaatatgcctgcaatgggtaatatcagccttaagagcagtgag360acatatgtctcataaaccagggaatccgctgctagtaaagcaaaaaacaaatgagtcata420tgaagattttgcagcaagactgctagaagcaatagatgcagagccagtagcacatcctat480aaaagaatatctaaaactaacgttgtcttatacgaatgcatcctcagattgtcagaagca540aatggatagaacactaggacaaagagtcaaacaagctagtgtagaacaaaaaa593<210>52<211>593<212>DNA<213>羊关节炎-脑炎病毒<400>52agccgtagattctgtaatgttccagcagctgcaaacagtagcaatgcagcatggcctcgt60gtcagaggactttgaaaggcttccagcatatcatgctactacctgggcaagtaaagatat120cttagaagtactggccatgatgcctggaaatagagctcaaaaagagttaattcaagggaa180attaaatgaagaagcagagaggtggagaaggaataatccaccacctccagcaggaggagg240gttaacagtggatcaaattatgggagtaggacaaacaaatcaggcagcggcacaagcaaa300catggatcaggcaagacaaatatgcctacaatgggtgatatcagcactaagagcagtaag360gcatatggctcacaagccagggaatccaatgttagtaaagcaaaaagcaaatgagccata420tgaagaatttgcagcaaggctgctggaagcaatagatgccgagccagttaatcagcccat480aaaagaatatctaaaactaacgttgtcttatacgaatgcatcctcagattgtcagaagca540aatggatagaacactaggacaaagagtcaaacaagctagtgtagaacaaaaaa593<210>53<211>720<212>DNA<213>羊关节炎-脑炎病毒<400>53atggtgagtctagatagagacatggcgaggcaagtctccggggggaaaagagattatcct60gagctcgaaaaatgtatcaagcatgcatgcaagataaaagttcgactcagaggggagcac120ttgacagaaggaaattgtttatggtgccttattacatgtttgaggaccataaagaggaac180cttggacaaaaaaacattagagtaaaatttaggacaatatggcagaaggtgaagaatcta240actcctgaggagagtaacaaaaaagactttatgtctttgcaggccacattagcgggtcta300atgtgttgccaaatggggatgagacctgagacattgcaagatgcaatggctacagtaatc360atgaaagatgggttactggaacaagaggaaaagaaggaagacaaaagagaaaaggaagag420agtgtcttcccaatagtagtgcaagcagcaggagggagaagctggaaagcagtagattct480gtaatgttccagcaactgcaaacagtagcaatgcagcatggcctcgtgtctgaggacttt540gaaaggcagttggcatattatgctactacctggacaagtaaagacatactagaagtattg600gccatgatgcctggaaatagagctcaaaaggagttaattcaagggaaattaaatgaagaa660gcagaaaggtggagaaggaataatccaccacctccagcaggaggaggattaacagtggat720720<210>54<211>129<212>DNA<213>羊关节炎-脑炎病毒<400>54cagcatggcctcgtgtccgaggactttgaaaggcagttggcatattatgctactacctgg60acaagtaaggacatattagaagtattggccatgatgccaggaaatagagctcaaaaggag120ctaattcaa129<210>55<211>129<212>DNA<213>羊关节炎-脑炎病毒<400>55cagcatggaatagtatcagaagagtttgagaggcaactgtcttattatgctaccacttgg60acaagcaaggatatcttagaggtactagccatgatgcctggcaatagagcattaaaagag120ctaatacaa129<210>56<211>129<212>DNA<213>羊关节炎-脑炎病毒<400>56caacatgggatagtatcagaggaatttgagagacaaatgtcttattatgctaccacatgg60acaagtaaggatattttagaagtactagcaatgatgcccgggaacagagcattaaaggag120ctgatacaa129<210>57<211>129<212>DNA<213>羊关节炎-脑炎病毒<400>57cagcatggactagtatcagaagaatttgaaaggcagctagcatactatgccacaacgtgg60acaagcaaagacatactagaggtgttagccatgatgccagggaatagagcacaaaaagaa120ctaatacaa129<210>58<211>129<212>DNA<213>羊关节炎-脑炎病毒<400>58cagcatggacttgtgtccgaagattttgagaggcaattggcatattatgctacaacctgg60actagtgaagatatattagaagtattggctatgatgcctgggaatagagcacagaaagaa120ttaatacaa129<210>59<211>1347<212>DNA<213>羊关节炎-脑炎病毒<400>59atggtgagtctagatagagacatggcgaggcaagtctccggggggaaaagagattatcct60gagctcgaaaaatgtatcaagcatgcatgcaagataaaagttcgactcagaggggagcac120ttgacagaaggaaattgtttatggtgccttaaaacattagattacatgtttgaggaccat180aaagaggaaccttggacaaaagtaaaatttaggacaatatggcagaaggtgaagaatcta240actcctgaggagagtaacaaaaaagactttatgtctttgcaggccacattagcgggtcta300atgtgttgccaaatggggatgagacctgagacattgcaagatgcaatggctacagtaatc360atgaaagatgggttactggaacaagaggaaaagaaggaagacaaaagagaaaaggaagag420agtgtcttcccaatagtagtgcaagcagcaggagggagaagctggaaagcagtagattct480gtaatgttccagcaactgcaaacagtagcaatgcagcatggcctcgtgtctgaggacttt540gaaaggcagttggcatattatgctactacctggacaagtaaagacatactagaagtattg600gccatgatgcctggaaatagagctcaaaaggagttaattcaagggaaattaaatgaagaa660gcagaaaggtggagaaggaataatccaccacctccagcaggaggaggattaacagtggat720caaattatgggggtaggacaaacaaatcaagcagcagcacaagctaacatggatcaggca780aggcaaatatgcctgcaatgggtaataaatgcattaagagcagtaagacatatggcgcac840aggccagggaatccaatgctagtaaagcaaaaaacgaatgagccatatgaagattttgca900gcaagactgctagaagcaatagatgcagagccagttacacagcctataaaagattatcta960aagctaacactatcttatacaaatgcatcagcagattgtcagaagcaaatggatagaaca1020ctaggacaaagagtacaacaagctagtgtagaagaaaaaatgcaagcatgtagagatgtg1080ggatcagaagggttcaaaatgcaattgttagcacaagcattaaggccaggaaaaggaaaa1140gggaatggacagccacaaaggtgttacaactgtggaaaaccgggacatcaagcaaggcaa1200tgtagacaaggaatcatatgtcacaactgtggaaagagaggacatatgcaaaaagaatgc1260agaggaaagagagacataaggggaaaacagcagggaaacgggaggagggggatacgtgtg1320gtgccgtccgctcctcctatggaataa1347<210>60<211>129<212>DNA<213>羊关节炎-脑炎病毒<400>60cagcatggcctcgtgtccgaggactttgaaaggcagttggcatattatgctactacctgg60acaagtaaggacatattagaagtattggccatgatgccaggaaatagagctcaaaaggag120ctaattcaa129<210>61<211>129<212>DNA<213>羊关节炎-脑炎病毒<400>61cagcatggaatagtatcagaagagtttgagaggcaactgtcttattatgctaccacttgg60acaagcaaggatatcttagaggtactagccatgatgcctggcaatagagcattaaaagag120ctaatacaa129<210>62<211>129<212>DNA<213>羊关节炎-脑炎病毒<400>62caacatgggatagtatcagaggaatttgagagacaaatgtcttattatgctaccacatgg60acaagtaaggatattttagaagtactagcaatgatgcccgggaacagagcattaaaggag120ctgatacaa129<210>63<211>129<212>DNA<213>羊关节炎-脑炎病毒<400>63cagcatggactagtatcagaagaatttgaaaggcagctagcatactatgccacaacgtgg60acaagcaaagacatactagaggtgttagccatgatgccagggaatagagcacaaaaagaa120ctaatacaa129<210>64<211>129<212>DNA<213>羊关节炎-脑炎病毒<400>64cagcatggacttgtgtccgaagattttgagaggcaattggcatattatgctacaacctgg60actagtgaagatatattagaagtattggctatgatgcctgggaatagagcacagaaagaa120ttaatacaa129<210>65<211>20<212>DNA<213>人工序列<220><223>用于构建dig-标记探针的引物<400>65ctggcgtaatagcgaagagg20<210>66<211>20<212>DNA<213>人工序列<220>用于构建dig-标记探针的引物<223>Primerusedtoconstructdig-labeledprobe<400>66aactcgccgcacatctgaac20<210>67<211>3911<212>DNA<213>人工序列<220><223>pCAH/SINd0<400>67atccagcacagtggcggccgctagcacaaaaataaaaaaagaaagggtggactgtgagac60atgggctaaagaggagcggccgctcgagtctagaactagtggatcagctttgctgcttgc120acttcagagttctaggagagtccctcctagtctctcctctccgaggaggtaccgagacct180caaaataaaggagtgattgccttactgccgagtggagagtgattactgagcggccggtgt240atcgggagtcgtcccttaatctgtgcaataccagagcggctctcgcagccgacctcgagg300gggggccctattctatagtgtcacctaaatgctagagctcgctgatcagcctcgactgtg360ccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaa420ggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagt480aggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaa540gacaatagcaggcatgctggggatgcggtgggctctatggcttctgaggcggaaagaacc600agtggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagc660aaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccatag720gctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaaccc780gacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgt840tccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgct900ttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctggg960ctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtct1020tgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggat1080tagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacgg1140ctacactagaaggacagtatttggtatctgcgctctgctgaagccagttaccttcggaaa1200aagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgt1260ttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttc1320tacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagatt1380atcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatcta1440aagtatatatgagtaacctgatcaggactcttccttttcatgaacaataaaactgtctgc1500ttacataaacagtaatacaaggggtgttatgagccatattcaacgggaaacgtcttgctc1560taggccgcgattaaattccaacatggatgctgatttatatgggtataaatgggctcgcga1620taatgtcgggcaatcaggtgcgacaatctatcgattgtatgggaagcccgatgcgccaga1680gttgtttctgaaacatggcaaaggtagcgttgccaatgatgttacagatgagatggtcag1740actaaactggctgacggaatttatgcctcttccgaccatcaagcattttatccgtactcc1800tgatgatgcatggttactcaccactgcgatccccgggaaaacagcattccaggtattaga1860agaatatcctgattcaggtgaaaatattgttgatgcgctggcagtgttcctgcgccggtt1920gcattcgattcctgtttgtaattgtccttttaacagcgatcgcgtatttcgtctcgctca1980ggcgcaatcacgaatgaataacggtttggttgatgcgagtgattttgatgacgagcgtaa2040tggctggcctgttgaacaagtctggaaagaaatgcataaacttttgccattctcaccgga2100ttcagtcgtcactcatggtgatttctcacttgataaccttatttttgacgaggggaaatt2160aataggttgtattgatgttggacgagtcggaatcgcagaccgataccaggatcttgccat2220cctatggaactgcctcggtgagttttctccttcattacagaaacggctttttcaaaaata2280tggtattgataatcctgatatgaataaattgcagtttcatttgatgctcgatgagttttt2340ctaagaattcgcgcaattaaccctcactaaagggaacaaaagctgggtaccgggcccgtt2400gacattgattattgactagttattaatagtaatcaattacggggtcattagttcatagcc2460catatatggagttccgcgttacataacttacggtaaatggcccgcctggctgaccgccca2520acgacccccgcccattgacgtcaataatgacgtatgttcccatagtaacgccaataggga2580ctttccattgacgtcaatgggtggagtatttacggtaaactgcccacttggcagtacatc2640aagtgtatcatatgccaagtacgccccctattgacgtcaatgacggtaaatggcccgcct2700ggcattatgcccagtacatgaccttatgggactttcctacttggcagtacatctacgtat2760tagtcatcgctattaccatggtgatgcggttttggcagtacatcaatgggcgtggatagc2820ggtttgactcacggggatttccaagtctccaccccattgacgtcaatgggagtttgtttt2880ggcaccaaaatcaacgggactttccaaaatgtcgtaacaactccgccccattgacgcaaa2940tgggcggtaggcgtgtacggtgggaggtctatataagcagagctcaagcttgctgcttgc3000acttcagagttctaggagagtccctcctagtctctcctctccgaggaggtaccgagacct3060caaaataaaggagtgattgccttactgccgagtggagagtgattactgagcggccggtgt3120atcgggagtcgtcccttaatctgtgcaataccagagcggctctcgcagctggcgcccaac3180gtggggcccgaggagaagaaaagaaagcggccctgagaactcggcttctgaaaaagagga3240agaggacaagttgctatagcaacaagagagaagaagtagagcaaaggtccagtggctcgg3300aaaaagaggaactgaaacttcggggacgcctgaaggagtaaggtaagtgactctgctgta3360cgcggggcgaggcagaggtttccttctaaattgaaagagaagtgttgctgcgagaggtct3420tggtggtcgagaatcctgtacaaaaaaaaggagggatctcggtcaggaccaggacccctg3480ggagtaatacaacagcaacaccgtaagaaaatccgcctagggaattcgattctagaggtg3540atagaaatgccagaaaactatgcaaaaacaagaatcataaacaggaaaaaaagagaactc3600agccacaagaggaagaagagaggcgttggcttggtcattatgctagttatcatggcaata3660gtagctgccgcaggggcttctctgggagtcgcaaacgcgattcagcagtcttacactaag3720gcagctgtccagacccttgctaatgcaactgctgcacagcaggatgtgttagaggcaacc3780tatgccatggtacagcatgtggctaaaggcgtacgaatcttggaagctcgagtggctcga3840gtggaagctatcacagatagaataatgctataccaagaattggattgttggcactaggat3900ccatcgccacc3911<210>68<211>4238<212>DNA<213>人工序列<220><223>pCAH/SINd1<400>68atccagcacagtggcggccgctagcacaaaaataaaaaaagaaagggtggactgtgagac60atgggctaaagaggagcggccgctcgagtctagaactagtggatcagctttgctgcttgc120acttcagagttctaggagagtccctcctagtctctcctctccgaggaggtaccgagacct180caaaataaaggagtgattgccttactgccgagtggagagtgattactgagcggccggtgt240atcgggagtcgtcccttaatctgtgcaataccagagcggctctcgcagccgacctcgagg300gggggccctattctatagtgtcacctaaatgctagagctcgctgatcagcctcgactgtg360ccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaa420ggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagt480aggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaa540gacaatagcaggcatgctggggatgcggtgggctctatggcttctgaggcggaaagaacc600agtggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagc660aaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccatag720gctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaaccc780gacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgt840tccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgct900ttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctggg960ctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtct1020tgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggat1080tagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacgg1140ctacactagaaggacagtatttggtatctgcgctctgctgaagccagttaccttcggaaa1200aagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgt1260ttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttc1320tacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagatt1380atcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatcta1440aagtatatatgagtaacctgatcaggactcttccttttcatgaacaataaaactgtctgc1500ttacataaacagtaatacaaggggtgttatgagccatattcaacgggaaacgtcttgctc1560taggccgcgattaaattccaacatggatgctgatttatatgggtataaatgggctcgcga1620taatgtcgggcaatcaggtgcgacaatctatcgattgtatgggaagcccgatgcgccaga1680gttgtttctgaaacatggcaaaggtagcgttgccaatgatgttacagatgagatggtcag1740actaaactggctgacggaatttatgcctcttccgaccatcaagcattttatccgtactcc1800tgatgatgcatggttactcaccactgcgatccccgggaaaacagcattccaggtattaga1860agaatatcctgattcaggtgaaaatattgttgatgcgctggcagtgttcctgcgccggtt1920gcattcgattcctgtttgtaattgtccttttaacagcgatcgcgtatttcgtctcgctca1980ggcgcaatcacgaatgaataacggtttggttgatgcgagtgattttgatgacgagcgtaa2040tggctggcctgttgaacaagtctggaaagaaatgcataaacttttgccattctcaccgga2100ttcagtcgtcactcatggtgatttctcacttgataaccttatttttgacgaggggaaatt2160aataggttgtattgatgttggacgagtcggaatcgcagaccgataccaggatcttgccat2220cctatggaactgcctcggtgagttttctccttcattacagaaacggctttttcaaaaata2280tggtattgataatcctgatatgaataaattgcagtttcatttgatgctcgatgagttttt2340ctaagaattcgcgcaattaaccctcactaaagggaacaaaagctgggtaccgggcccgtt2400gacattgattattgactagttattaatagtaatcaattacggggtcattagttcatagcc2460catatatggagttccgcgttacataacttacggtaaatggcccgcctggctgaccgccca2520acgacccccgcccattgacgtcaataatgacgtatgttcccatagtaacgccaataggga2580ctttccattgacgtcaatgggtggagtatttacggtaaactgcccacttggcagtacatc2640aagtgtatcatatgccaagtacgccccctattgacgtcaatgacggtaaatggcccgcct2700ggcattatgcccagtacatgaccttatgggactttcctacttggcagtacatctacgtat2760tagtcatcgctattaccatggtgatgcggttttggcagtacatcaatgggcgtggatagc2820ggtttgactcacggggatttccaagtctccaccccattgacgtcaatgggagtttgtttt2880ggcaccaaaatcaacgggactttccaaaatgtcgtaacaactccgccccattgacgcaaa2940tgggcggtaggcgtgtacggtgggaggtctatataagcagagctcaagcttgctgcttgc3000acttcagagttctaggagagtccctcctagtctctcctctccgaggaggtaccgagacct3060caaaataaaggagtgattgccttactgccgagtggagagtgattactgagcggccggtgt3120atcgggagtcgtcccttaatctgtgcaataccagagcggctctcgcagctggcgcccaac3180gtggggcccgaggagaagaaaagaaagcggccctgagaactcggcttctgaaaaagagga3240agaggacaagttgctatagcaacaagagagaagaagtagagcaaaggtccagtggctcgg3300aaaaagaggaactgaaacttcggggacgcctgaaggagtaaggtaagtgactctgctgta3360cgcggggcgaggcagaggtttccttctaaattgaaagagaagtgttgctgcgagaggtct3420tggtggtcgagaatcctgtacaaaaaaaaggagggatctcggtcaggaccaggacccctg3480ggagtaatacaacagcaacaccgtaagaaaatccgcctaggtgagtctagatagagacta3540ggcgaggcaagtctccggggggaaaagagattatcctgagctcgaaaaatgtatcaagca3600tgcatgcaagataaaagttcgactcagaggggagcacttgacagaaggaaattgtttatg3660gtgccttaaaacattagattacatgtttgaggaccataaagaggaaccttggacaaaagt3720aaaatttaggacaatatggcagaaggtgaagaatctaactcctgaggagagtaacaaaaa3780agactttatgtctttgcaggccacattagcgggtctaatgtgttgccaaatggggatgag3840acctgcaggaattcgattctagaggtgatagaaatgccagaaaactatgcaaaaacaaga3900atcataaacaggaaaaaaagag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ataaacttttgccattctcaccggattcagtcgtcactcatggtgatttctcact7860tgataaccttatttttgacgaggggaaattaataggttgtattgatgttggacgagtcgg7920aatcgcagaccgataccaggatcttgccatcctatggaactgcctcggtgagttttctcc7980ttcattacagaaacggctttttcaaaaatatggtattgataatcctgatatgaataaatt8040gcagtttcatttgatgctcgatgagtttttctaagaattcgcgcaattaaccctcactaa8100agggaacaaaagctgggtaccgggccc812权利要求1.转移载体,其包含(a)羊关节炎-脑炎病毒(CAEV)包装序列,其基本由以下组成(i)CAEV5’LTR和CAEVgag-编码序列之间的非翻译区以及(ii)连接到所述非翻译区3’端的CAEVgag-编码序列的核苷酸1至X,其中X小于613;以及(b)多聚腺苷酸化、RNA转运、逆转录和整合所需的顺式作用元件,其与所述包装序列可操作性连接。2.权利要求1的转移载体,其中X选自60、100、125、150、175、200、225、250、275、300、325、350、375、400、425、450、475、500、525、550、575和600。3.权利要求1的转移载体,其中X选自(a)X大于25且小于600,(b)X大于25且小于500,(c)X大于25且小于400,(d)X大于25且小于300,(e)X大于25且小于200,(f)X大于50且小于600,(g)X大于50且小于500,(h)X大于50且小于400,(i)X大于50且小于300,(j)X大于50且小于200,(k)X大于75且小于600,(l)X大于75且小于500,(m)X大于75且小于400,(n)X大于75且小于300,(o)X大于75且小于200,(p)X大于100且小于600,(q)X大于100且小于500,(r)X大于100且小于400,(s)X大于100且小于300,(t)X大于100且小于200,(u)X大于125且小于600,(v)X大于125且小于500,(w)X大于125且小于400,(x)X大于125且小于300,(y)X大于125且小于200,(z)X大于150且小于600,(aa)X大于150且小于500,(bb)X大于150且小于400,(cc)X大于150且小于300,(dd)X大于150且小于200,(ee)X大于200且小于600,(ff)X大于200且小于500,(gg)X大于200且小于400,(hh)X大于200且小于300,(ii)X大于200且小于200,(jj)X大于250且小于600,(kk)X大于250且小于500,(ll)X大于250且小于400,和(mm)X大于250且小于300。4.权利要求1的转移载体,其中X大于40且小于613。5.权利要求1的转移载体,其中X大于57且小于613。6.权利要求1的转移载体,其中X约为327。7.权利要求1的转移载体,其中gag-编码序列的起始密码子被突变以防止gag蛋白的翻译。8.权利要求7的转移载体,其中所述起始密码子突变成TAG。9.权利要求7的转移载体,其中位于起始密码子ATG下游X碱基对处的gag-编码序列的ATG密码子被突变以防止gag蛋白的翻译,其中X小于30。10.权利要求9的转移载体,其中X约为21。11.权利要求1的转移载体,其还包含RRE区。12.权利要求1的转移载体,其还包含CAEV3’LTR,其中U3区被删除。13.权利要求1的转移载体,其还包含异源启动子。14.权利要求13的转移载体,其中异源启动子是人巨细胞病毒的主要立即早期启动子(HCMVMIEP)。15.权利要求1的转移载体,其中所述载体具有图3C所示的pCAH/SINd1结构。16.权利要求1的转移载体,其还包含转录盒。17.权利要求16的转移载体,其中所述转录盒包含可操作性连接至异源启动子的感兴趣多聚核苷酸。18.一种载体系统,其包含权利要求1的转移载体以及包装载体系统,其中所述包装载体系统包含含有CAEVgag-pol-编码序列和RRE的第一多聚核苷酸,以及含有病毒包膜编码序列的笫二多聚核苷酸。19.权利要求18的载体系统,其中所述转移载体还包含转录盒。20.权利要求19的载体系统,其中所述转录盒包含可操作性连接至异源启动子的感兴趣多聚核苷酸。21.权利要求18的载体系统,其中所述病毒包膜-编码序列是非CAEV包膜-编码序列。22.权利要求21的载体系统,其中所述非CAEV包膜-编码序列是VSV-G-编码序列或GaL-V编码序列。23.权利要求22的载体系统,其中所述包膜-编码序列是VSV-G-编码序列。24.权利要求22的载体系统,其中所述包膜-编码序列是GaL-V编码序列。25.权利要求18的载体系统,其中所述载体系统还包含含有rev-编码序列的第三多聚核苷酸序列。26.权利要求18或25的载体系统,其中所述载体系统还包含含有vif-编码序列的第四多聚核苷酸序列。27.权利要求18、25或26任一项的载体系统,其中所述第一多聚核苷酸还包含可操作性连接至所述CAEVgag-pol-编码序列的异源调节序列。28.权利要求18、21或22任一项的载体系统,其中所述第二多聚核苷酸还包含可操作性连接至所述病毒包膜-编码序列的异源调节序列。29.权利要求18的载体系统,其中所述第一多聚核苷酸还包含可操作性连接至所述CAEVgag-pol-编码序列的异源调节序列,并且第二多聚核苷酸还包含可操作性连接至所述病毒包膜-编码序列的异源调节序列。30.权利要求25的载体系统,其中所述第三多聚核苷酸还包含可操作性连接至所述rev-编码序列的异源调节序列。31.权利要求26的载体系统,其中所述第四多聚核苷酸还包含可操作性连接至所述vif-编码序列的异源调节序列。32.权利要求27、28、29、30或31的载体系统,其中所述异源调节序列是启动子。33.权利要求18的载体系统,其中所述包装载体系统缺失有功能的CAEV包装序列。34.权利要求18的载体系统,其中所述包装载体系统缺失剪接供体位点和gag起始密码子之间的CAEV基因组5’端。35.权利要求18的载体系统,其包含含有第一多聚核苷酸的第一载体和含有第二多聚核苷酸的第二载体。36.权利要求25的载体系统,其包含含有所述第一多聚核苷酸的第一载体、含有所述第二多聚核苷酸的第二载体和含有所述第三多聚核苷酸的第三载体。37.权利要求26的载体系统,其包含含有所述第一多聚核苷酸的第一载体、含有所述第二多聚核苷酸的第二载体、含有所述第三多聚核苷酸的第三载体以及含有所述第四多聚核苷酸的第四载体。38.权利要求25的载体系统,其包含含有所述第一多聚核苷酸和所述第三多聚核苷酸的第一载体、以及含有所述第二多聚核苷酸的第二载体。39.权利要求26的载体系统,其包含含有所述第一多聚核苷酸和所述第四多聚核苷酸的第一载体、以及含有所述第二多聚核苷酸的第二载体。40.权利要求32的载体系统,其中所述CAEVgag-pol-编码序列可操作性连接至MCMVMIEP启动子。41.权利要求40的载体系统,其中所述第一载体具有图2A所示的pMGP/RRE结构。42.权利要求35的载体系统,其中所述病毒包膜-编码序列是可操作性连接至HCMVMIEP启动子的VSV-G-编码序列,并且其中所述第二载体还包含β-珠蛋白内含子。43.权利要求42的载体系统,其中所述第二载体具有图6A所示的pHGVSV-G结构。44.权利要求35的载体系统,其中所述病毒包膜-编码序列是可操作性连接至MCMVMIEP启动子的GaLV-编码序列,并且其中所述第二载体还包含真核延伸因子-1alpha内含子。45.权利要求44的载体系统,其中所述第二载体具有图6B所示的pMYKEF-1/env结构。46.权利要求36的载体系统,其中所述第三载体具有图5所示的pHYK/rev结构。47.权利要求37的载体系统,其中所述第四载体具有图4所示的pHYK/vif结构。48.生产基于CAEV的载体颗粒的方法,其包括(a)用权利要求20的载体系统转染细胞;(b)在适合生产基于CAEV的慢病毒载体颗粒的条件下孵育所述细胞,其中载体颗粒具有感染性和转导能力并且是复制缺陷型的;和(c)回收所述载体颗粒。49.权利要求48的方法生产的载体颗粒。50.包含权利要求49的载体颗粒和媒介体的组合物。51.包含权利要求18-47中任一项的载体系统的药盒。52.将多肽递送入哺乳动物细胞的方法,其包括使所述哺乳动物细胞与权利要求49的载体颗粒接触。53.权利要求52的方法,其中所述细胞在细胞与载体颗粒接触之前从哺乳动物中分离。54.权利要求52的方法,其中所述哺乳动物细胞是分裂细胞。55.权利要求52的方法,其中所述哺乳动物细胞是非分裂细胞。56.权利要求52的方法,其中所述哺乳动物细胞是CD34+干细胞。57.将多肽递送入脊椎动物的方法,其包括向所述脊椎动物施用权利要求49的载体颗粒。58.包含权利要求1-17中任一项的转移载体的药盒。59.权利要求18-47中任一项的载体系统,其还包含含有所述第一多聚核苷酸的细胞。60.权利要求28、30、32、36或38中任一项的载体系统,其还包含含有所述第一和第三多聚核苷酸的细胞。61.权利要求26-28、31-32、37、39、41、43或45中任一项的载体系统,其还包含含有所述第一和第四多聚核苷酸的细胞。62.权利要求26-28、31-32、37、39、41、43或45中任一项的载体系统,其还包含含有所述第一、第三和第四多聚核苷酸的细胞。63.权利要求18-24、26、29、33-35、40、42、44或46中任一项的载体系统,其还包含含有所述第一和第二多聚核苷酸的细胞。64.权利要求25-28、30、32、36、或38中任一项的载体系统,其还包含含有所述第一、第二和第三多聚核苷酸的细胞。65.权利要求26-28、31-32、37、39、41、43或45中任一项的载体系统,其还包含含有所述第一、第二和第四多聚核苷酸的细胞。66.权利要求26-28、31-32、37、39、41、43或45中任一项的载体系统,其还包含含有所述第一、第二、第三和第四多聚核苷酸的细胞。67.权利要求35-47中任一项的载体系统,其还包含含有所述第一和第二载体的细胞。68.权利要求36-46中任一项的载体系统,其还包含含有所述第一、第二和第三载体的细胞。69.权利要求36-47中任一项的载体系统,其还包含含有所述第一、第二、第三和第四载体的细胞。70.权利要求35-47中任一项的载体系统,其还包含含有所述第一载体的细胞。71.生产基于CAEV的载体颗粒的方法,其包括(a)制备包含CAEVgag-pol-编码序列和RRE的细胞;(b)用权利要求17的转移载体转染所述细胞;(c)在适合生产基于CAEV的慢病毒载体颗粒的条件下孵育所述细胞,其中载体颗粒具有感染性和转导能力并且是复制缺陷型的;和(d)回收所述载体颗粒。72.含有CAEV包装序列的载体,其中所述CAEV包装序列基本由以下组成(a)CAEV5’LTR和CAEVgag-编码序列之间的非翻译区,以及(b)连接到所述非翻译区3’端的CAEVgag-编码序列的核苷酸1至X,其中X小于613。73.权利要求15的转移载体,其中所述载体与SEQIDNO68具有至少70%一致性。74.权利要求41的载体系统,其中所述第一载体与SEQIDNO77具有至少70%一致性。75.权利要求43的载体系统,其中所述第二载体与SEQIDNO74具有至少70%一致性。76.权利要求45的载体系统,其中所述第二载体与SEQIDNO72具有至少70%一致性。77.权利要求46的载体系统,其中所述第三载体与SEQIDNO75具有至少70%一致性。78.权利要求47的载体系统,其中所述第四载体与SEQIDNO76具有至少70%一致性。全文摘要本发明涉及可用于向非分裂和分裂细胞递送核酸的基于羊关节炎-脑炎病毒的载体和载体系统。本发明还公开了应用该载体系统向非分裂和分裂细胞递送核酸的方法。文档编号C12N15/63GK101014710SQ200480043938公开日2007年8月8日申请日期2004年9月7日优先权日2004年9月7日发明者李修京,金连洙,金钟必申请人:株式会社Macrogen
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