CN1809381A - 具有稀有二硫化物结构的hiv-1包膜糖蛋白 - Google Patents
具有稀有二硫化物结构的hiv-1包膜糖蛋白 Download PDFInfo
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- CN1809381A CN1809381A CNA2004800163060A CN200480016306A CN1809381A CN 1809381 A CN1809381 A CN 1809381A CN A2004800163060 A CNA2004800163060 A CN A2004800163060A CN 200480016306 A CN200480016306 A CN 200480016306A CN 1809381 A CN1809381 A CN 1809381A
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Abstract
本发明提供了一种具有稀有二硫化物结构的HIV-1包膜糖蛋白。特别地,本发明包括gp120多肽,编码该多肽的多聚核苷酸,以及相关载体,宿主细胞,和表达方法。本发明还包括含有gp120多肽或多聚核苷酸的免疫原性组合物及其在诱发gp120特异的免疫反应中的应用。本发明的gp120多肽和多聚核苷酸也可用于本发明的诊断方法中。
Description
相关申请的交联参考
本申请要求2003年6月12日提交的美国临时申请No.60/477,815的优先权,该申请全文通过引用而并入本申请。
关于在联邦政府赞助的研究和发展下产生的本发明的权利的声明
本发明是在政府的小型商业研究经费(SBIR)No.4 R44AI052624-02的支持下完成的。在本发明中政府具有一定的权利。
技术领域
本发明主要涉及用于诱发或检测对1型人免疫缺陷病毒(HIV-1)的包膜糖蛋白:gp120和/或gp160发生免疫反应的免疫原性的组合物的领域。特别地,本发明涉及包括含有gp120序列的多肽和/或编码此多肽的多聚核苷酸(RNA或DNA)的免疫原性的组合物,其中该组合物诱发可用于预防或治疗HIV-1感染和/或疾病(AIDS)的免疫反应。
技术背景
获得性免疫缺陷综合征(AIDS)是由被鉴定为人免疫缺陷病毒(HIV)的逆转录病毒引起的。人们已经花了很大力气在诱导抗体或细胞反应的基础上开发诱导保护性免疫反应的疫苗。出于安全考虑,最近的努力都放在亚单位疫苗上,其中HIV蛋白质,而不是减弱或杀死的病毒被用作疫苗中的免疫原。亚单位疫苗通常包括gp120,其为HIV包膜蛋白质的一部分,存在于病毒体和病毒感染细胞的表面。在这方面,gp120通过游离的病毒体或通过细胞—细胞间的融合来调节HIV-1的感染。在这两种情况下,gp120通过与两个细胞受体结合而启动HIV-1感染:两个受体一个是CD4另一个是趋化因子受体(典型地CCR5或CXCR4)。CD4和趋化因子受体的不同的高亲和性结合位点位于gp120分子的表面。
HIV包膜蛋白质已近被广泛地描述了,来源于大量HIV株的HIV包膜蛋白质的氨基酸和核苷酸序列是已知的。gp120分子包括60,000道尔顿的核心多肽,其大量地被N-连接的糖基化修饰从而使分子量增加至120,000道尔顿。成熟HIV-1包膜蛋白质,gp120和gp41均来源于一个相同的前体,gp160。gp160前体含有指导在与膜结合的核糖体上合成蛋白质并保证新合成的多肽向内质网内腔迁移(分泌路径)的氨基端信号序列。在内质网上,信号序列被信号肽酶清除,在协同移位过程中,蛋白质需要“简单的”高甘露糖型的N连接的碳水化合物。而后含有碳水化合物的蛋白质被运输到高尔基体上,在高尔基体上大量高甘露糖型碳水化合物被转化成“复合的”含唾液酸的碳水化合物。另外,通过弗林(furin)或类弗林肽酶在保守的糖蛋白切割位点的蛋白质水解作用而使gp160转化成gp120/gp41复合物。然后gp120/gp41复合物被运输到细胞表面,认为该复合物在细胞表面形成三聚体结构。在细胞或病毒体的膜上,gp120通过非共价作用与gp41相连而作为周围膜蛋白。相反地,gp41是一种整合膜蛋白,其通过位于近羧基末端的疏水跨膜区锚定在膜双层上。
gp120的氨基酸序列包括5个相对保守的结构域(C1-C5),其中分布有5个超变区(V1-V5)。在gp120的一级序列中18位半胱氨酸残基的位置和gp120序列中的大约24个N-连接的糖基化位点中的13个位置在大多数gp120序列中是保守的。超变区包括大量的氨基酸取代、插入和缺失。这些结构域序列的不同最多达到不同病毒分离体的gp120分子间序列变异性的约30%。尽管有变异,所有的gp120保留了与gp140结合并结合CD4和趋化因子(CCR5和CXCR4)受体而诱导病毒与宿主细胞膜融合的病毒能力。
发明内容
本发明提供了一种免疫原性组合物,其包括分离的多肽、或分离的多聚核苷酸以及其药学上可接受的运载体。分离的多肽包括,或者分离的多聚核苷酸编码,第一gp120氨基酸序列,其中第一gp120序列包括至少gp120的V2、V3和CV4区域结构域和:(i)第一gp120序列在一个或多个下述位点中缺少一个或多个半胱氨酸残基:54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418和445;和/或(ii)第一gp120序列在除下述位点以外的位点包括一个或多个附加的半胱氨酸残基:24,,29,,34,,54,,74,,119,,126,,131,,157,,196,,205,,218,,228,,239,,247,,296,,331,,378,,385,,418,,445,,493,,495,,499-501,,503-508,和510,,计数是从HIV gp120的HXB-2族株的gp120的蛋甲硫氨酸的N端开始。可是然而,第一gp120序列不是在V1区域结构域具有一个或多个附加的半胱氨酸的G亚型的gp120序列的G亚型或在V4区域结构域具有一个或多个附加的半胱氨酸的E亚型的gp120序列的E亚型。在一个优选的实施例方案中,第一gp120序列额外地包括V1区域结构域。
在一个实施方案例中,第一gp120序列在一个或多个下述位点中缺少一个或多个半胱氨酸残基:54,,74,,119,,126,,157,,205,,218,,228,,239,,247,,331,,378,或385。
在另一个实施例方案中,如果一个或多个附加的半胱氨酸残基不存在于gp120的V1区域结构域,那么第一gp120序列在除下述位点以外的位点包括一个或多个附加的半胱氨酸残基:54,,74,,119,,126,,131,,157,,196,,205,,218,,228,,239,,247,,296,,331,,378,,385,,418,,或445。
第一gp120序列可以包括自然存在的gp120序列,并且优选地,包括来自于原始分离的HIV的gp120序列。在一个优选的实施方案例中,第一gp120序列与选自下列序列组的gp120的每一个V1,V2,V3和C4区结构域至少具有约为99%的同一性:SEQID NO:2,,4,,6,,8,,10,,12,,14,,16,,18,,20,,22,,24,,26,,28,,30,,32,,34,,36,,38,,40,,42,,44,,46,,48,,50,,52,,54,56,,58,,60,,62,,64,,66,,68,,70,,72,,74,,76,,78,,80,,82,,84,,86,,88,,90,,92,,94,,96,,98,,100,,102,,104,,106,,108,,110,,112,,114,,116,,118,,120,,122,,124,,126,,128,,130,,132,,134和136。在一个更优选的实施方案例中,第一gp120序列包括至少选自下列组序列的gp120的V1,V2,,V3和C4区域结构域:SEQ ID NO:2,,4,,6,,8,,10,,12,,14,,16,,18,,20,,22,,24,,26,,28,,30,,32,,34,,36,,38,,40,,42,,44,,46,,48,,50,,52,,54,,56,,58,,60,,62,,64,,66,,68,,70,,72,,74,,76,,78,,80,,82,,84,,86,,88,,90,,92,,94,,96,,98,,100,,102,,104,,106,,108,,110,,112,,114,,116,,118,,120,,1122,,124,,126,,128,,130,,132,,134,和136。
在一个优选的实施方案例中,第一gp120序列包括奇数个半胱氨酸。在此实施方案例的变型中,免疫原组合物免疫原性的组合物包括含有第一gp120序列的多肽,并且在第一gp120序列中的半胱氨酸与共价结合到另一个多肽共价结合,优选通过二硫键。其他的多肽可以包括在第二gp120序列。当第二gp120序列与第一gp120序列相同时,第一、第二gp120序列形成同源二聚体。当第二gp120序列与第一gp120序列不同,第一、第二gp120序列形成异源二聚体。其他的多肽可以令外地、或可选择地包括gp41氨基酸序列。
本发明还提供了免疫原组合物免疫原性的组合物,其包括含有第一gp120序列的多肽,其中gp120序列中的一个半胱氨酸与选自细胞特异性结合半族、药物、免疫刺激性寡核苷酸(即,CpG)或免疫原运载体蛋白的试剂以共价键结合。
在某种实施方案例中,免疫原组合物免疫原性的组合物包括多肽,其包括,或多聚核苷酸编码包括含有第一gp120序列的融合多肽。
如果需要,免疫原组合物免疫原性的组合物可以额外地包括佐剂。
本发明还提供了一种个分离的包括第一gp120氨基酸序列的分离多肽,其中第一gp120序列包括至少gp120的V2,V3和C4区域结构域和:(a)第一gp120序列在一个或多个下述位点中缺少一个或多个半胱氨酸残基:54,,74,,119,,126,,157,,205,,218,,228,,239,,247,,331,,378,或385;和/或(b)如果一个或多个附加的半胱氨酸残基不存在于gp120的V1区域结构域,第一gp120序列在除去下述位点以外的位点包括一个或多个附加的半胱氨酸残基:54,,74,,119,,126,,131,,157,,196,,205,,218,,228,,239,,247,,296,,331,,378,,385,,418,或445,,计数是从HIVgp120的HXB-2族株的gp120的N端蛋甲硫氨酸的N端开始。可是然而,第一gp120序列不是在V4区域结构域具有一个或多个附加的半胱氨酸的gp120序列的E亚型。在一个优选的实施方案例中,第一gp120序列额外地包括V1区域结构域。
在一个实施方案例中,分离多肽包括在一个或多个下列位点中缺少一个或多个半胱氨酸残基的第一gp120序列:54,,74,,119,,126,,157,,205,,218,,228,,239,,247,,331,,378,或385。在另一个实施方案例中,如果一个或多个附加的半胱氨酸残基不存在于gp120的V1区域结构域,分离多肽包括在除下列位点以外的位点含有一个或多个额外的半胱氨酸残基的第一gp120序列:54,,74,,119,,126,,131,,157,,196,,205,,218,,228,,239,,247,,296,,331,,378,,385,,418,or 445。
在一个优选的实施方案例中,分离多肽包括第一gp120氨基酸序列,该第一gp120序列与选自下组列序列的gp120的V1,,V2,,V3和C4区域结构域的每一个的每一个具有至少约为99%的同一性:SEQ BD IDNO:2,,4,,6,,8,,10,,12,,14,,16,,18,,20,,22,,24,,26,,28,,30,,32,,34,,36,,38,,40,,42,,44,,46,,48,,50,,52,,54,,56,,58,,60,,62,,64,,66,,68,,70,,72,,74,,76,,78,,80,,82,,84,,86,,88,,90,,92,,94,,96,,98,,100,,102,,104,,106,,108,,110,,112,,114,,116,,118,,120,,122,,124,,126,,128,,130,,132,,134,,和136。在一个更优选的实施方案例中,第一gp120序列包括至少选自下组列序列的gp120的V1,,V2,,V3和C4区域结构域:SEQ ID NO:2,,4,,6,,8,,10,,12,,14,,16,,18,,20,,22,,24,,26,,28,,30,,32,,34,,36,,38,,40,,42,,44,,46,,48,,50,,52,,54,,56,,58,,60,,62,,64,,66,,68,,70,,72,,74,,76,,78,,80,,82,,84,,86,,88,,90,,92,,94,,96,,98,,100,,102,,104,,106,,108,,110,,112,,114,,116,,118,,120,,122,,124,,126,,128,,130,,132,,134,,和136。
在一个优选的实施方案例中,分离多肽包括具有奇数个半胱氨酸的第一gp120序列。在本实施方案例的变形中,第一gp120序列中的一个半胱氨酸与其他多肽共价结合,优选通过二硫键。其他多肽可以包括第二gp120序列。当第二gp120序列与第一gp120序列相同时,第一、第二gp120序列形成同源二聚体。当第二gp120序列与第一gp120序列不同,第一、第二gp120序列形成异源二聚体。其他的多肽可以另外地、或可选择地包括gp41氨基酸序列。
本发明还提供了分离多肽,其中gp120序列中的半胱氨酸与选自细胞特异性结合半族、药物、免疫刺激性寡核苷酸(即,CpG)或免疫原运载体蛋白的试剂以共价键结合。
在某种实施方案中,分离多肽包括包含第一gp120序列的融合多肽。融合多肽可以包括异源信号序列,如单纯疱疹病毒糖蛋白D(gD-1)信号序列或人组织血浆酶原激活因子信号序列。融合蛋白可以另外地、或可选择地包括附加表位。
本发明还提供了编码本发明的任何多肽的分离的多聚核苷酸。如果试图用于表达编码的多肽,多聚核苷酸优选为用于在特异种的宿主细胞中表达的优化的外显子最优密码子。在一个优选的实施方案例中,多聚核苷酸编码一个gp120序列,其与选自下组列序列的gp120的V1,,V2,,V3和C4区域结构域的每一个具有至少约为99%同一性的gp120序列:SEQ ID NO:2,,4,,6,,8,,10,,12,,14,,16,,18,,20,,22,,24,,26,,28,,30,,32,,34,,36,,38,,40,,42,,44,,46,,48,,50,,52,,54,,56,,58,,60,,62,,64,,66,,68,,70,,72,,74,,76,,78,,80,,82,,84,,86,,88,,90,,92,,94,,96,,98,,100,,102,,104,,106,,108,,110,,112,,114,,116,,118,,120,,122,,124,,126,,128,,130,,132,,134,和136。在一个更优选的实施方案例中,多聚核苷酸包括选自下组列序列的gp120核苷酸序列:SEQ ID NO:1,,3,,5,,7,,9,,11,,13,,15,,17,,19,,21,,23,,25,,27,,29,,31,,33,,35,,37,,39,,41,,43,,45,,47,,49,,51,,53,,55,,57,,59,,61,,63,,65,,67,,69,,71,,73,,75,,77,,79,,81,,83,,85,,87,,89,,91,,93,,95,,97,,99,,101,,103,,105,,107,,109,,111,,113,,115,,117,,119,,121,,123,,125,,127,,129,,131,,133,,135或其亚序列,其中亚序列编码至少gp120的V1,,V2,,V3和C4区域结构域。
本发明的其他方面包括包含本发明的任何多聚核苷酸的载体和含有载体的宿主细胞。本发明的优选载体包括表达载体和病毒载体。优选的宿主细胞包括哺乳动物和细菌细胞。
本发明还提供一种产生制备包括第一gp120氨基酸序列的多肽的方法。在一个实施方案例中,该方法具体为:(a)将本发明的载体导入细胞;(b)表达多肽。细胞可以在体内或是培养的。如果是培养的,此方法可额外地包括从培养物中回收多肽。在另一个实施方案例中,多肽可以通过以下方法制备:(a)培养本发明的宿主细胞,其中宿主细胞包括一个表达载体,且宿主细胞在适于多肽表达的条件下被培养;(b)从培养物中回收多肽。
本发明的另一方面包括使用含有第一gp120序列的多肽免疫动物的方法。此方法包括将免疫原组合物免疫原性的组合物投药给动物。
本发明还提供了一种诊断方法,其包括将从被治疗者来的生物样品接触与,:(a)含有gp120氨基酸序列的分离多肽;(b)确定样品是否含有可特异性结合该分离多肽的抗体。gp120含有至少gp120的V2,V3和C4结构域以及:(i)在下列一个或多个下列位点缺少一个或多个半胱氨酸残基:54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418,和445;和/或(ii)在除以下位点之外的位点上包括一个或多个半胱氨酸残基:24,29,34,54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418,445,493,495,499-501,503-508和510,计数是从HIV gp120的HXB-2株的gp120的N端的甲硫氨酸甲硫氨酸开始。然而,第一gp120序列不是在V1结构域具有一个或多个附加的半胱氨酸的gp120序列的G亚型或在V4结构域具有一个或多个附加的半胱氨酸的gp120序列的E亚型。在一个优选的实施方案中,第一gp120序列额外地包括V1结构域。
在一个可选择的实施方案中,本发明提供了一种诊断方法,其包括分析从被治疗者来的生物样品被治疗者,以确定该样品是否含有多肽,或多聚核苷酸编码,其具有稀有数量的半胱氨酸的gp120氨基酸序列。更特别地,分析样品的gp120氨基酸序列:即该序列(a)在一个或多个下述位点中缺少一个或多个半胱氨酸残基:54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418and 445;和/或(b)在除下述位点以外的位点包括一个或多个附加的半胱氨酸残基:24,29,34,54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418,445,493,495,499-501,503-508和510;计数是从HIV gp120的HXB-2株的gp120的N端的甲硫氨酸开始。优选地,gp120序列不是在V1结构域具有一个或多个附加的半胱氨酸的gp120序列的G亚型或在V4结构域具有一个或多个附加的半胱氨酸的gp120序列的E亚型。
在本实施方案的一个变形中,分析是一种在适于结合的条件下使样品与特异性结合gp120序列的抗体接触的免疫分析。
在本实施方案的另一个变形中,分析是基于多聚核苷酸的分析,其中在适合杂交的条件下,样品多聚核苷酸与特异性地与编码gp120序列的核苷酸杂交的核酸分子接触。在一个优选的实施方案中,核酸分子可以是扩增引物对中的一个,在这种情况下,通过在适合扩增的条件下使样品多聚核苷酸与两个扩增引物接触来进行分析,然后测定该扩增产物是否被生成。在另一个优选的实施方案中,核酸分子是固定在固相的核酸探针,通过测定样品多聚核苷酸是否特异性地与核酸探针杂交而进行分析。
附图说明
附图出示了HIV-1gp120氨基酸序列的模式图。对于所有的图,每个氨基酸残基位置的数字是关于HIV-1株HXB2的。线表示突变的氨基酸残基,使用标准的单个字母的缩写标明氨基酸残基。所有的突变以下列形式标明,以表示一个残基取代另一个:X->Y在位置Z(HXB2),其中X是被取代的氨基酸,Y是取代(即,新的)氨基酸。5个可变和5个保守结构域分别用V1-V5和C1-C5表示。
图1:在样品U-101c1中,54和126号位置的Cys被取代,Cys残基被取代为Arg残基。总的半胱氨酸补充(cysteine complement)是16个残基。
图2:在样品U-178c13中,131和228号位置的Cys被取代,Cys残基分别被取代为Arg和Tyr残基。总的半胱氨酸补体是16个残基。
图3:出示了具有总半胱氨酸补体为17个残基的HIV-1样品。每一次突变后样品名在括号内表示。
图4:出示了具有总半胱氨酸补体为19个残基的HIV-1样品。每一次突变后样品名在括号内表示。
图5A-X:出示了具有总半胱氨酸补体为20个残基的HIV-1样品。样品名在每一个示意图下表示。在这个组图中,仅仅表示了具有额外的Cys残基的区域。在A-S图中,链内的残基数(Cys残基除外)在图的下面右侧部分表示。代表U-374c1和U-234c10的T图,代表以额外的半胱氨酸为基础的一套潜在的二级结构。U图显示了以不同的半胱氨酸对为基础的U-374c1和U-208_4c1的不同构象。还描述了在V2(U-033c1)(图V),V4(U-210c2)(图W)和V5(U-062_2c5)(图X)中的额外半胱氨酸残基。
具体实施方式
本发明提供了一种包括HIV gp120序列的分离多肽。这些gp120序列具有稀有的二硫化物结构。特别地,本发明的gp120序列包括多于或少于通常的18个半胱氨酸残基。此处描述的gp120序列来源于整个北美、波多黎各和荷兰的61处临床诊所进行的大规模的HIV疫苗的临床检测。在这些研究过程中,克隆并测序了来自350名HIV新近感染者的gp120编码cDNA。在这些研究中,血浆样品采自6个月内的感染者,血浆病毒RNA被逆转录,并通过聚合酶链反应(PCR)进行扩增和测序。令人惊奇的是,在所获得的gp120序列中,大约20%具有稀有的二硫化物结构。因此,发现在病毒感染早期,并在宿主内发生广泛的突变之前,此结构特性在成功的病毒感染中具有显著的数量。因此,具有稀有的二硫化物结构的病毒可以代表与新近感染相关的“传播显性”或在北美传播的HIV-1的主要的新的变种。在两种情况下,用于预防HIV-1感染的疫苗都应该被设计成对抗含有稀有的二硫化物结构的gp120的病毒。
含有奇数个半胱氨酸的天然发生的蛋白质很少见,这是因为巯基自由基与其它游离巯基具有高度的反应性,因此易于在分子内或分子间合形成二硫键。本发明的含有奇数个半胱氨酸的gp120序列非常有意义,因为不成对的半胱氨酸残基可以形成额外的分子间或内二硫键,并且可以表现一种先前未被描述的病毒产生分子多样性的机制。原则上,此种多样性可以通过改变分子内或分子间的二硫化物结构、通过调节两个gp120分子间(每一个都具有一个不成对的半胱氨酸残基)的共价连接、通过调节与gp41中的半胱氨酸残基的共价连接或通过调节与其它病毒或细胞蛋白的共价连接而实现。
而且,在病毒体或病毒感染细胞表面产生更加精确复制的gp120/gp41复合体结构的新抗原时,疫苗生产者可以使用含有不成对的半胱氨酸残基的HIV-1包膜蛋白。例如,HIV-1病毒体和病毒感染细胞表面的病毒刺被认为是单体的gp120/gp41复合体的非共价键的低聚物(常常为二聚体)。因为这些复合体是脆弱且易分离,不可能纯化单体的或低聚的gp120/gp41复合体。然而,如果能够发展一种产生低聚的gp120/gp41复合体的方法,则应该相信可以生产超HIV-1疫苗。事实上,为了生产稳定的、共价结合的gp120/gp41复合体,一些研究者已经应用体外变异来向gp120和gp41结构中导入不成对的半胱氨酸残基。尽管得到了共价连接的复合体,所得到的结构不是天然发生的,因此不能精确地复制如病毒体或病毒感染细胞上的gp120/gp41复合体结构。因为本申请中所描述的许多分子是天然发生的,且在远离先前用于生产二硫化物稳定的gp120/gp41复合体的限定区域具有不成对的半胱氨酸,因此这些分子提供了一个独特的基因生产多种二硫键结构以增强gp120免疫原性的机会。实施例的结构包括同源二聚体、gp120/gp41异源二聚体、gp120共价连接到其它HIV-1蛋白、gp120连接到非HIV-1蛋白、或gp120共价连接到非蛋白质化学组合物。这些结构可增强单体达不到的免疫原性。异源二聚体gp120复合体用于扩大免疫反应的宽度。例如,含有从两个不同HIV-1亚型来源的gp120序列的异源二聚体可以被用于诱发对每种HIV-1亚型的免疫反应。在另一个实施方案中,含有自由巯基的gp120序列可以被连接到其他半族,如连接到特定细胞类型(即,树突细胞或巨噬细胞)或可增强免疫反应的(即,将gp120序列连接到高免疫原性的载体蛋白,如白喉毒素、匙孔血蓝蛋白、甲状腺球蛋白、或牛血清白蛋白)的靶gp120序列。因为gp120与细胞表面的CD4抗原高亲和性地结合,含有自由疏基的gp120序列可以与定位于含有CD4细胞的药物结合。
定义
除非特别指出,权力要求和说明书中的术语在下面定义。
全长gp120氨基酸序列是指如果序列含有超过大多数全长gp120序列所具有的18个半胱氨酸残基,则其具有一个或多个“额外的半胱氨酸”。gp120片断也是指如果其来源的全长gp120序列含有超过通常所具有的18个半胱氨酸残基则在片断中含有“额外半胱氨酸”,并且有一个或多个另外的半胱氨酸。
术语“免疫原性组合物”是指能够诱发免疫反应的任何组合物。
在此应用的术语“疫苗”指可减少风险、或预防感染物引起的感染(“预防性疫苗”)或可在某种程度上减轻已存在的感染(“治疗性疫苗”)的免疫原性组合物。如果疫苗可防止机体不受感染物的继发的感染,则该疫苗称“预防性”。
如此处所用的,术语“DNA疫苗”是指含有一个或多个编码抗原的多聚核苷酸的疫苗,向有机体投药多聚核苷酸可导致其所编码抗原的表达,及随后对该抗原的免疫反应。
如此处所用的,术语“病毒来源的疫苗”是指含有病毒颗粒、类病毒颗粒(VLP)、病毒颗粒或VLP的一部分和/或在其表面呈现抗原的病毒感染的细胞的疫苗,其中,向有机体投药颗粒或细胞可以诱发对该提呈抗原的免疫反应。术语“病毒来源的疫苗”包括含有两个或多个不同来源的成分的嵌合病毒颗粒或VLP。
术语“多肽”和“蛋白质”在此可互换使用,其指氨基酸的聚合体,除非特别限定,其包括与天然氨基酸具有相似功能的不典型氨基酸。
如对应多肽或多聚核苷酸使用的术语“分离的”指从典型地与多肽或多聚核苷酸共同存在的至少一种其他成分中分离出来的多肽或多聚核苷酸。因此,如果从至少一种天然地与多肽或多聚核苷酸共同存在的成分中纯化出多肽或多聚核苷酸,天然存在的多肽就被分离出来。,如果多肽或多聚核苷酸从生产多肽或多聚核苷酸时就存在的至少一种其它成分中纯化出来,重组多肽或多聚核苷酸就被分离出来。
术语“氨基酸”或“氨基酸残基”除非特别说明,包括天然发生的L-氨基酸或残基。在此处应用通常所用的一个或三个字母的缩写(Lehninger,A.L.(1975)Biochemistry,2d ed.,pp.71-92,WorthPublishers,N.Y.)。术语“氨基酸”或“氨基酸残基”包括D-氨基酸以及化学修饰的氨基酸,如氨基酸类似物、天然发生的不常常组成蛋白质的氨基酸、以及具有氨基酸特性的化学合成的化合物(共同地称“不典型“氨基酸)。例如,允许具有相同的如含有天然Phe或Pro的多肽化合物所限制的构象的苯丙氨酸或脯氨酸的类似物或模拟物,也包括在“氨基酸”的定义内。
示范性的非典型的氨基酸例如包括在国际公布的WO90/01940中描述的以及2-氨基脂肪酸(Aad),其可以取代Glu和Asp;2-氨基庚二酸(Apm)取代Glu和Asp;2-氨基丁酸(Abu)取代Met,Leu和其他脂肪族的氨基酸;2-氨基庚酸(Ahe)取代Met,Leu和其他脂肪族的氨基酸;2-氨基异丁酸(Aib)取代Gly;环己胺(Cha)取代Val,Leu和Ile;高精氨酸(Har)取代Arg和Lys;2,3-二胺基丙酸(Dpr)取代Lys,Arg和His;N-乙基甘氨酸(EtGly)取代Gly,Pro和Ala;N-乙基天冬酰胺酸(EtAsn取代Asn和Gln;羟基赖氨酸(Hyl)取代Lys;别羟基赖氨酸(Ahyl)取代Lys;3-(和4-)羟基脯氨酸(3Hyp,4Hyp)取代Pro,Ser和Thr;别-异亮氨酸(Aile)取代Ile,Leu和Val;脒基苯丙氨酸(amidinophenylalanine)取代Ala;N-甲基甘氨酸(MeGly,肌氨酸)取代Gly,Pro和Ala;N-甲基异亮氨酸(MeIle)取代Ile;正缬氨酸(Nva)取代Met和其他脂肪族的氨基酸;正亮氨酸(Nle)取代Met和其他脂肪族的氨基酸;鸟氨酸(Orn)取代Lys,Arg和His;;瓜氨酸(Cit)和甲硫氨酸亚砜(MSO)取代Thr,Asn和Gln;N-甲基苯丙氨酸(MePhe),三甲基苯丙氨酸,卤代(F,Cl,Br和I)苯丙氨酸和三氟苯丙氨酸取代Phe。
提及多肽的术语“全长”指具有与成熟的野生型多肽相同长度的多肽。
在此关于多肽或多聚核苷酸的术语“片段”指大分子的一部分。因此多肽片段可以缺少大分子的N末端、C末端或两者。多肽片断在此也指“多肽”。一个多核苷酸片段可以缺少大分子的5’端、3’端或两者。多核苷酸片断在此也指“寡核苷酸”。寡核苷酸是相对短的核苷酸分子,通常小于200个核苷酸,更特别地,小于100个核苷酸,最更特别地,小于50个核苷酸。典型地,寡核苷酸是单链DNA分子。
氨基酸或核苷酸序列的“亚序列”是一个较大序列的一部分。
在两个或多个氨基酸或核苷酸序列中的术语“同一的”或“同一性百分比”是指在应用以下的序列运算法则或用眼观察的测量中,在比较或比对最大对应性时,两个或多个序列或亚序列相同或具有特定的氨基酸或核苷酸相同序列的百分比。
在序列对比时,典型地,一个序列作为对照,另一个被测序列与其对比。当应用序列对比运算法则时,将被测和对照序列输入电脑,如果需要,指出亚序列的同等物,并设定序列比对的参数。然后,序列对比运算法则根据指定的参数,计算出被测序列相对于对照序列的序列同一性的百分比。
用于对比的最佳序列队列可以通过,如Smith & Waterman,Adv.Appl.Math.2:482(1981)的局部同一性运算法则,Needleman &Wunsch,J.Mol.Biol.48:443(1970)的同一性对比运算法则,Pearson & Lipman(1988)Proc.Natl.Acad.Sci.USA 85:2444的相似性方法的研究,电脑执行的这些运算法则(在the WisconsinGenetics Software Package,Genetics Computer Group,575 ScienceDr.,Madison WI中的GAP,BESTFIT,FASTA和TFASTA),或通过用眼观察(详见Ausubel等.,supra)而进行。
一个有用的运算法则的例子是PILEUP。PILEUP应用累进的成对的比对从相关序列组中产生多个比对序列以显示序列的关系和同一性的百分比。它也能做出用于产生比对的簇关系的树图或系统图。PILEUP应用Feng & Doolittle(1987)J.Mol.Evol.35:351-360的简化的累进比对方法。所应用的方法与Higgins & Sharp(1989)CABIOS 5:151-153描述的方法相似。该程序可比对最多300个序列,每个最长可以有5000个核苷酸或氨基酸。多重比对过程以两个最相似的序列的成对的比对开始,产生了两个比对序列的簇。然后将该簇与下一个最相关的序列或比对的序列簇比对。通过将两个独立序列的成对比对简单的延伸来进行两个序列簇的比对。通过一系列的累进的、成对的比对完成最终比对。通过指定序列对比区域的特定的序列和他们的氨基酸或核苷酸同等物以及指定程序参数来运行程序。例如,参照序列可以与其他的被测序列对比,应用下列参数确定序列同一性关系的百分比:间隙重量默认值(3.00)(default gap weight),间隙长度重量默认值(0.10)(default gap length weight)以及重量的末端间隙(weighted end gap)。
另一个确定序列同一性和序列相似性百分比的运行法则的例子是在Altschul等.(1990)J.Mol.Biol.215:403-410中描述的BLAST运行法则(Basic Local Alignment Search Tool)。用于BLAST分析的软件可以在国家生物信息中心获得(http://www.ncbi.nlm.nih.gov/)。该运行法则包括首先通过在询问程序中鉴别长度W的短字来鉴别高得分序列对(HSP),当与数据库序列的相同长度的字比对时,其符合或满足一些阳性评估阈值T。T指相邻字得分的阈值(Altschul等,supra)。这些最初的相邻的字的采样数作为种子启动了对包含他们的更长的HSP的查找。然后字的采样数沿着每个序列向两个方向延伸直到累积到能被增加到的比对分数。对于核苷酸,累积分数应用参数M(匹配残基对的报酬分数;常常大于0)和N(错误配对残基的惩罚分数;常常小于0)来计算。对于氨基酸序列,分数矩阵常常被用来计算累积分数。在每个方向上的字的采样数的延伸在以下情况下终止:通过数量X离开其能达到的最大值而使累积比对分数降低;由于一个或多个累积的负分数残基比对导致了累积分数达到0或0以下;或序列到头了。BLAST运算法则的参数W,T和X决定了比对的灵敏性和速度。BLASTN程序(用于核酸序列)的字的长度默认参数(W)为11,期望值(E)为10,M=5,N=-4,且对比两条链。对于氨基酸序列,BLASTP程序的字长度默认参数(W)为3,期望值(E)为10,BLOSUM62分数矩阵(参照Henikoff & Henikoff(1989)Proc.Natl.Acad.,Sci.USA89:10915)。
除了计算序列同一性之外,BLAST运算法则还可以进行两个序列间相似性的统计学分析(详见Karlin & Altschul(1993)Proc.Natl.Acad.Sci.USA,90:5873-5787)。由BLAST运算法则提供的一个相似性检测是最小和可能性(P(N)),其提供了一个可能性的指标,该可能性是指两个核苷酸或氨基酸之间发生配对的几率。例如,如果在被测序列与对照序列的比较中,最小和可能性小于大约0.1,更优选小于大约0.01,最优选小于大约0.001,则认为核酸与对照序列相似。
如果两个或多个多肽残基是同源的(即,在一级、二级或三级结构中占相似的位置)或类似的(即,具有相同或相似的功能特性),则它们被称为“对应”。如本领域所熟知的,同源残基可以通过如前所述的比对多肽序列查找最大对应来决定。
在本发明中描述的gp120氨基酸序列的位置通过位置号被确定,其中计数是从HIV的HXB-2株(SEQ ID NO:138)的gp120N端的甲硫氨酸开始的。
如果其它氨基酸残基取代了通常在那个位点上的半胱氨酸或半胱氨酸被删除了,则Gp120氨基酸序列被称为在特定位点缺少半胱氨酸。
关于多肽中的术语“野生型”指具有一个存在于天然有机体的多肽中的氨基酸序列的任何多肽,不考虑分子的来源;也就是,术语“野生型”指序列特征,而不考虑分子是否来自于天然来源;应用重组技术被表达,而后纯化;或被合成。
术语“氨基酸序列变异”指通过添加、缺失或取代氨基酸而具有不同于野生型氨基酸序列的氨基酸序列的多肽。
在此处应用的术语“保守的氨基酸取代”是指用同等功能的氨基酸取代氨基酸。功能相同的氨基酸通常在大小和/或性质(如,电荷或疏水性)与它们的取代物相似。相似特性的氨基酸可被分为下组:
(1)疏水的:His,Trp,Tyr,Phe,Met,Leu,Ile,Val,Ala;
(2)中性疏水的:Cys,Ser,Thr;
(3)极性的:Ser,Thr,Asn,Gln;
(4)酸性的/带负电的:Asp,Glu;
(5)带电荷的:Asp,Glu,Arg,Lys,His;
(6)碱性的/带正电的:Arg,Lys,His;
(7)碱性的:Asn,Gln,His,Lys,Arg;
(8)影响链取向的残基:Gly,Pro;
(9)芳香族的:Trp,Tyr,Phe,His。
下表出示了示范的和优选的保守的氨基酸取代
原始的残基 | 示范的保守氨基酸取代 | 优选的保守氨基酸取代 |
AlaArgAsnAspCysGlnGluGlyHisIleLeuLysMetPheProSerThrTrpTyrVal | Val,Leu,IleLys,Gln,AsnGln,His,Lys,ArgGluSerAsnAspProAsn,Gln,Lys,ArgLeu,Val,Met,Ala,PheIle,Val,Met,Ala,PheArg,Gln,AsnLeu,Phe,IleLeu,Val,Ile,AlaGlyThrSerTyrTrp,Phe,Thr,SerIle,Leu,Met,Phe,Ala | ValLysGlnGluSerAsnAspProAsnLeuIleArgLeuLeuGlyThrSerTyrPheLeu |
“信号序列”是在细胞膜上和分泌蛋白上发现的氨基酸序列,其指导蛋白质合成到膜结合的核糖体并介导新合成的多肽链向内质网内腔运动,在其中可以进行在细胞质中游离的核糖体上合成的蛋白质所不能进行的多种翻译后修饰。如在重组表达中所应用的,多肽从表达该肽的细胞分泌到培养介质以易于提纯。如果信号序列来源于其它的多肽并融合到多肽从而利于重组表达或分泌的时,此信号序列被称为“异源性的”。
“附加表位”是一个限定了对抗体的表位的氨基酸序列。附加表位可以被整合到感兴趣的多肽或肽上以利于纯化或检测。
如在此处所应用的“融合多肽”是指包括连接有一个通常在该多肽中并不存在的氨基酸序列上的多肽来源的氨基酸序列的多肽。后者可以为来自不同多肽的氨基酸序列(如异源信号序列)或人工序列。一般而言,应用重组技术表达多肽,该重组技术利用构建含有编码一个多肽序列的核酸序列,在框架上,其融合与编码其它多肽序列的核酸序列。
如用于多肽或多肽片段中的术语“衍生物”包括氨基酸序列变异以及其它任何通过一个或多个化学基团的添加、缺失或取代而不同于野生型氨基酸序列的其他分子。“衍生物”保留了野生型多肽或多肽片段的致少一个生物学或免疫学特性,例如,特异地结合受体的生物学特性和特异地结合抗体的免疫学特性。
“细胞特异结合半族”是指可特异地结合一个或多个特定细胞类型的半族。例如,细胞特异结合半族可以被连接到多肽或多聚核苷酸上,从而将多肽或多聚核苷酸引导到所需类型的细胞上。
“免疫原性载体蛋白”是与抗原连接的多肽,该抗原自身并不能诱发显著的免疫反应(如,半抗原)。结合的结果是能诱导对半抗原的免疫反应。
术语“特异结合”在此被定义为在特定的位点结合的伙伴与其对象(如,两个多肽,一个多肽和核苷酸分子,或两个核苷酸分子)的优先结合。术语“特异地结合”指对于靶分子或序列结合的优先性(即,亲和性)至少为非特异靶分子(即缺少特异性识别位点的随机产生的分子)的2倍,更优选至少为5倍,最优选至少为10倍或20倍。
如在此应用的,“抗体”指由基本上由免疫球蛋白基因或免疫球蛋白基因片段编码的一个或多个多肽组成的蛋白质。被鉴定的免疫球蛋白基因包括kappa,lambda,alpha,gamma,delta,epsilon和mu保守区基因,以及无数个免疫球蛋白可变区基因。轻链被分为kappa或lambda。重链被分为gamma,mu,alpha,delta或epsilon,其依次分别定义了免疫球蛋白的类别:IgG,IgM,IgA,IgD和IgE。
已知典型的免疫球蛋白结构包括四聚物。每一个四聚物有两对相同的多肽链组成,每一对具有一个“轻”链(约25kD)和一个“重”链(约50-70kD)。每个链的N末端是一个主要用于抗体识别的大约100-110或更多氨基酸的可变区。术语“可变的轻链”(VL)和“可变的重链”(VH)分别指这些轻链和重链。
抗体作为完整的免疫球蛋白或作为由多种多肽酶消化产生的已被确认的片断存在。因此,例如,胃蛋白酶消化抗体铰链区下方的二硫键连接从而产生一个Fab的二聚体F(ab)’2,其自身是一个通过二硫键连接到VH-CH1的轻链。F(ab)’2在温和的条件下可以被还原以打破铰链区的二硫键连接,因而将F(ab)’2二聚体转化成Fab’单体。Fab’单体是主要是Fab以及含有部分的铰链区(参见FundamentalImmunology,W.E.Paul,ed.,Raven Press,N.Y.(1993),祥见其他抗体片段的描述)。尽管是从一个完整的抗体消化的方面定义各种抗体片段的,技术人员应该认识到这些Fab’抗体也可以在体外通过化学或重组DNA方法合成。因此,在此应用的术语抗体也包括通过修饰完整的抗体或应用重组DNA方法在体外合成的抗体片段。优选的抗体包括单链抗体(作为单链多肽存在的抗体),更优选单链Fv抗体(sFv或scFv),其中可变区的重链和可变区的轻链连接在一起(直接或通过多肽连接)形成连续的多肽。单链Fv抗体是共价键连接的VH-VL异源二聚体,其可以从包括VH-和VL-编码序列的核酸序列被表达,直接或通过编码多肽连接子连接。Huston,等(1988)Proc.Nat.Acad.Sci.USA,85:5879-5883。尽管VH和VL被连接形成一个多肽链,VH和VL结构域以非共价键相关。scFv抗体和许多其他结构转变成天然地聚集,但是从抗体V结构域化学地分开轻链和重链多肽使其形成折叠成基本上类似于本领域技术人员熟知的抗体结合部位的三维结构的分子(见,如U.S.Patent Nos.5091513,5132405和4956778)。
词组“有效量”和“足够的量”是指产生预期生物学活性的生物学活性剂的量。
术语“药学上可接受的”是指足以对细胞没有毒性和/或被治疗者以允许可医药学应用的任何试剂。
术语“佐剂”指增强对抗原的免疫反应的化合物或混合物。
HIV的“原始分离物”是指从感染HIV个体获得的未经细胞培养的HIV分离物。
术语“多聚核苷酸”指脱氧核糖核酸或核糖核酸的聚合体,除非特别限定,其包括已知的与天然核苷酸有类似功能的天然核苷酸的类似物。术语“多聚核苷酸”指任何形式的DNA或RNA,例如包括,基因组DNA;互补DNA(cDNA),其为代表mRNA的DNA,通常通过信使RNA(mRNA)的逆转录或扩增获得;由合成或扩增产生的DNA分子和mRNA。术语“多聚核苷酸”包括双链核苷酸分子,以及单链分子。在双链多聚核苷酸分子中,多聚核苷酸的链不需要共同延伸(即,双链多聚核苷酸不需要沿着双链的全长都是双链)。
此处的术语“载体”指含有多聚核苷酸的DNA构建。优选的载体可以被稳定地复制或瞬时地导入宿主细胞。例如,载体可以是质粒,粘粒,细菌人造染色体(BAC),酵母人造染色体(YAC)或病毒载体。一旦被导入恰当的宿主,载体可以不依赖于宿主基因组而独立地复制和发挥功能,或在某些情况下,整合到宿主基因组。
此处的术语“可操作的连接”是指在对照序列(典型地为启动子)和被连接序列间的功能性连接。例如,如果启动子能够启动被连接序列的转录,该启动子被可操作的连接到该序列。
“表达载体”指含有被连接到在恰当的宿主细胞内可以有效地表达该多聚核苷酸的对照序列的多聚核苷酸的DNA构建。示范的对照序列包括有效转录的启动子,一个控制转录的可选择的操纵子,一个编码恰当的mRNA核糖体结合位点的序列和控制转录和翻译中止的序列。
术语“宿主细胞”指可以瞬时或稳定地含有载体的细胞。本发明的宿主细胞包括,但不局限于,细菌细胞,酵母细胞,昆虫细胞,植物细胞和哺乳动物细胞。其他的本领域中熟知的或开始知道的宿主细胞也适合用于本发明。
“宿主细胞”可以是细胞培养的,或可选地,在体内的。当其存在于活的有机体内时,该宿主细胞为体内。
如此处所用的,术语“互补”指在两个核苷酸间精确配对。即,如果一个核酸分子的指定位置的核苷酸可以通过氢键与另一个核酸分子的核苷酸结合,则认为两个核酸分子在此位点相互互补。术语“基本上互补”指在严格的杂交条件下序列彼此间互补足以形成特定的杂交物。
词组“严格的杂交条件”通常指在限定的离子强度和pH的前提下,温度比特定序列的融熔温度(Tm)低5度。可以实现大多数序列的特异杂交的示范的严格条件是温度至少为60度,盐浓度为0.2mol,pH7.0。
“特异杂交”指在严格限定的条件下使核苷酸分子与靶核酸序列结合而基本上不与杂交混合物中的其他核酸序列结合。本领域技术人员知道放宽杂交条件允许可容忍的序列错配。
分离具有稀有二硫化物结构的gp120多肽
本发明提供了一种包含第一gp120氨基酸序列的分离多肽。该分离多肽可以包括一个或多个额外的序列,因此分离多肽可以包括一个全长的gp160序列或一个含有gp160片段的gp120序列。第一gp120序列可以是全长的gp120序列或其片段。用于本发明的gp120片段至少包括gp120的V2,V3和C4结构域。在一个优选的实施方案中,gp120片段还包括V1结构域。gp120序列缺少一个或多个存在于大多数gp120序列中的18个半胱氨酸或含有一个或多个额外的半胱氨酸。
本发明的gp120多肽可以被用作本发明的诱发gp120特异性免疫反应的免疫原性组合物的成分。在一个优选的实施方案中,gp120可用作疫苗抗原。多肽可以以各种形式包含在疫苗中,如,游离形式,共价结合到特异细胞半族或免疫原性载体蛋白,或存在于病毒颗粒表面(作为病毒衍生的疫苗)。另外,携带药物的gp120多肽可以被用来将药物定位于含有CD4或趋化因子受体的细胞。
本发明的gp120多肽还可以用于确定一个标本是否含有针对指定的具有稀有二硫化物结构的gp120多肽的特异性抗体的诊断。
进一步,本发明合适的多肽可以在gp120免疫分析中被用作标准。更特别地,本发明的与用于分析的抗HIV-1抗体发生交叉反应的任何多肽可以被用作阳性对照,当检查一个标本是否存在gp120时,该对照可以与所得检查结果进行比较。
A.gp120多肽的类型
在第一个实施方案中,第一gp120序列在一个或多个下列位点中缺少一个或多个半胱氨酸残基:54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418,和445,计数是从HIV gp120的HXB-2株的gp120的N端的甲硫氨酸开始。在本实施方案的一个优选的变型中,第一gp120序列在一个或多个下列位点中缺少一个或多个半胱氨酸残基:54,74,119,126,157,205,218,228,239,247,331,378和385。
在第二个实施方案中,第一gp120序列在除下述位点以外的位点包括一个或多个附加的半胱氨酸残基:24,29,34,54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418,445,493,495,499-501,503-508和510,计数是以HXB-2gp120为基础的。可是,本发明的第一gp120序列不是在V1结构域具有一个或多个附加的半胱氨酸的gp120序列的G亚型,也不是在V4结构域具有一个或多个附加的半胱氨酸的gp120序列的E亚型。在本实施方案的一个优选的变型中,如果一个或多个附加的半胱氨酸残基不存在于gp120的V1区,则第一gp120序列在除下述位点以外的位点包括一个或多个附加的半胱氨酸残基:54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418和445。
本发明还包括这两种实施方案的结合,即,其中第一gp120序列在第一实施方案所述位点缺少一个或多个半胱氨酸并在第二实施方案所述位点包含一个或多个附加的半胱氨酸。
在一个优选的实施方案中,第一gp120序列具有相对于选自以下列序列的gp120序列的V2,V3和C4结构域的每一个的至少大约80%、大约85%、大约90%、大约95%或大约99%的同一性:SEQ ID NO:2,4,6,8,10,12,14,16,18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48,50,52,54,56,58,60,62,64,66,68,70,72,74,76,78,80,82,84,86,88,90,92,94,96,98,100,102,104,106,108,110,112,114,116,118,120,122,124,126,128,130,132,134和136。这些gp120序列采自北美、波多黎各和荷兰的61处临床诊所进行的大规模的HIV疫苗的临床检测。下表1出示了SEQ ID NO与来自检测的gp120样品间的对应性。HIV-1的HXB-2株的gp120的氨基酸序列是SEQ ID NO:138。
在一个更优选的实施方案中,第一gp120序列具有相对于选自这些序列之一的V1,V2,V3和C4结构域的每一个的至少大约80%、大约85%、大约90%、大约95%、大约99%的同一性。当这些结构域的每一个的同一性百分比至少为大约80%、大约85%、大约90%、大约95%或大约99%或更高时,此要求可以被满足。如从HXB-2N端的甲硫氨酸计数,这些结构域的末端如下:V1:残基131-157;V2:残基157 to 196;V3:残基296 to 331;C4:残基418 to 445。在这些实施方案的一个特别的例子中,第一gp120序列至少包括选自下列序列的V1,V2,V3和C4结构域:SEQ ID NO:2,4,6,8,10,12,14,16,18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48,50,52,54,56,58,60,62,64,66,68,70,72,74,76,78,80,82,84,86,88,90,92,94,96,98,100,102,104,106,108,110,112,114,116,118,120,122,124,126,128,130,132,134和136。
表1.HIV-1 gp120 DNA和蛋白质序列的序列ID号
SEQ ID NO | HIV-1 gp120样品/序列类型 |
1 | U-101c1/DNA |
2 | U-101c1/蛋白质 |
3 | U-178c13/DNA |
4 | U-178c13/蛋白质 |
5 | U-013c6/DNA |
6 | U-013c6/蛋白质 |
7 | U-016c1/DNA |
8 | U-016c1/蛋白质 |
9 | U-032_3c4/DNA |
10 | U-032_3c4/蛋白质 |
11 | U-051c1/DNA |
12 | U-051c1/蛋白质 |
13 | U-052c1/DNA |
14 | U-052c1/蛋白质 |
15 | U-065_3c1/DNA |
16 | U-065_3c1/蛋白质 |
17 | U-074c12/DNA |
18 | U-074c12/蛋白质 |
19 | U-093c1/DNA |
20 | U-093c1/蛋白质 |
21 | U-106c4/DNA |
22 | U-106c4/蛋白质 |
23 | U-117c1/DNA |
24 | U-117c1/蛋白质 |
25 | U-124_2c1/DNA |
26 | U-124_2c1/蛋白质 |
27 | U-145c1/DNA |
28 | U-145c1/蛋白质 |
29 | U-171c11/DNA |
30 | U-171c11/蛋白质 |
31 | U-174c11/DNA |
32 | U-174c11/蛋白质 |
33 | U-177c11/DNA |
34 | U-177c11/蛋白质 |
35 | U-218c14/DNA |
36 | U-218c14/蛋白质 |
37 | U-228c1/DNA |
38 | U-228c1/蛋白质 |
39 | U-241_2c2/DNA |
40 | U-241_2c2/蛋白质 |
41 | U-242c1/DNA |
42 | U-242c1/蛋白质 |
43 | U-257c1/DNA |
44 | U-257c1/蛋白质 |
45 | U-267_2c10/DNA |
46 | U-267_2c10/蛋白质 |
47 | U-300_3c1/DNA |
48 | U-300_3c1/蛋白质 |
49 | U-302c17/DNA |
50 | U-302c17/蛋白质 |
51 | U-305c1/DNA |
52 | U-305c1/蛋白质 |
53 | U-323c11/DNA |
54 | U-323c11/蛋白质 |
55 | U-334c3/DNA |
56 | U-334c3/蛋白质 |
57 | U-349c2/DNA |
58 | U-349c2/蛋白质 |
59 | U-350c1/DNA |
60 | U-350c1/蛋白质 |
61 | U-386_2c1/DNA |
62 | U-386_2c1/蛋白质 |
63 | U-031_2c10/DNA |
64 | U-031_2c10/蛋白质 |
65 | U-064c1/DNA |
66 | U-064c1/蛋白质 |
67 | U-099c6/DNA |
68 | U-099c6/蛋白质 |
69 | U-148_2c1/DNA |
70 | U-148_2c1/蛋白质 |
71 | U-183_2c1/DNA |
72 | U-183_2c1/蛋白质 |
73 | U-209c3/DNA |
74 | U-209c3/蛋白质 |
75 | U-212c11/DNA |
76 | U-212c11/蛋白质 |
77 | U-294c30/DNA |
78 | U-294c30/蛋白质 |
79 | U-307c1/DNA |
80 | U-307c1/蛋白质 |
81 | U-312c4/DNA |
82 | U-312c4/蛋白质 |
83 | U-313c1/DNA |
84 | U-313c1/蛋白质 |
85 | U-317_2c1/DNA |
86 | U-317_2c1/蛋白质 |
87 | U-343c3/DNA |
88 | U-343c3/蛋白质 |
89 | U-344c1/DNA |
90 | U-344c1/蛋白质 |
91 | U-363c2/DNA |
92 | U-363c2/蛋白质 |
93 | U-033c1/DNA |
94 | U-033c1/蛋白质 |
95 | U-060c4/DNA |
96 | U-060c4/蛋白质 |
97 | U-062_2c5/DNA |
98 | U-062_2c5/蛋白质 |
99 | U-071c11/DNA |
100 | U-071c11/蛋白质 |
101 | U-104_3c1/DNA |
102 | U-104_3c1/蛋白质 |
103 | U-141c1/DNA |
104 | U-141c1/蛋白质 |
105 | U-165c1/DNA |
106 | U-165c1/蛋白质 |
107 | U-187c1/DNA |
108 | U-187c1/蛋白质 |
109 | U-195c1/DNA |
110 | U-195c1/蛋白质 |
111 | U-208_4c1/DNA |
112 | U-208_4c1/蛋白质 |
113 | U-210c2/DNA |
114 | U-210c2/蛋白质 |
115 | U-215_2c1/DNA |
116 | U-215_2c1/蛋白质 |
117 | U-234c10/DNA |
118 | U-234c10/蛋白质 |
119 | U-236c2/DNA |
120 | U-236c2/蛋白质 |
121 | U-260c3/DNA |
122 | U-260c3/蛋白质 |
123 | U-275c1/DNA |
124 | U-275c1/蛋白质 |
125 | U-279c1/DNA |
126 | U-279c1/蛋白质 |
127 | U-284c3/DNA |
128 | U-284c3/蛋白质 |
129 | U-306c1/DNA |
130 | U-306c1/蛋白质 |
131 | U-332c14/DNA |
132 | U-332c14/蛋白质 |
133 | U-356c1/DNA |
134 | U-356c1/蛋白质 |
135 | U-374c1/DNA |
136 | U-374c1/蛋白质 |
137 | HXB-2/DNA |
138 | HXB-2/蛋白质 |
Gp120氨基酸序列可以是天然发生的(即,野生型)氨基酸序列或野生型多肽相应区域的变异氨基酸序列。在一个实施方案中,gp120氨基酸序列来源于HIV-1的原始分离物。本发明优选的多肽通常包括野生型gp120氨基酸序列或含有如上述的保守氨基酸取代的gp120氨基酸序列。
本发明的多肽可以包括除gp120氨基酸序列以外的其他氨基酸序列,即,来源于异源蛋白的氨基酸序列。从而,本发明包括融合蛋白,其中gp120氨基酸序列在任一端或两端被融合到来自一个或多个异源蛋白的氨基酸序列。常常被引入感兴趣蛋白的附加氨基酸序列的例子包括信号序列,其有助于蛋白质和附加表位的分泌,可以被用于免疫检测或亲和性纯化。用于本发明的优选的信号序列包括,但不局限于,单纯疱疹病毒糖蛋白D(HSV gD-1)信号序列和人组织血浆酶原激活因子信号序列。示范的附加表位包括绿色荧光蛋白,红细胞凝聚素,或FLAG附加表位和六组氨酸或相似的金属亲和簇。当HSV gD-1信号序列被用于促进分泌时,HSV gD-1序列的N端可以很方便地被用作附加表位。
本发明的多肽还可以被修饰以产生保留了诱发gp120特异的免疫反应功能的衍生物。例如,本领域技术人员认识到很多技术可以用来构建与相应的多肽复合物具有相同或相似所需生物学活性而被称为“肽模拟”的物质,但该物质比多肽具有更好的活性,如,溶解性,稳定性,和对水解和蛋白质水解的易感性。例如参见,Morgan,等,Ann.Rep.Med.Chem.,24:243-252(1989)。从而,本发明的多肽包括,例如在N端氨基、在C端羧基修饰的和/或多肽中的其中一个或多个酰胺键转变为非非酰胺键连接。
在一个特定的实施方案中,本发明的多肽包括具有奇数个半胱氨酸残基数的第一gp120序列。此序列至少具有一个“游离”半胱氨酸(即,不形成分子间二硫键的一个半胱氨酸)。游离半胱氨酸可以与其他多肽共价键结合。例如,游离半胱氨酸可以与其他多肽中的游离半胱氨酸形成二硫键。例如,可以应用定点突变的方法很方便地将一个游离半胱氨酸插入任何一个感兴趣的多肽中。其他多肽可以包括第二gp120序列,其可与第一gp120序列相同或不同。两个相同gp120序列间的二硫键结合产生一个同源二聚体。两个不同gp120序列间的二硫键结合产生一个异源二聚体。
在本实施方案的一个变型中,第一gp120序列中的游离半胱氨酸与含有gp41氨基酸序列的另一个多肽共价键结合。优选地,第一gp120序列通过二硫键结合到gp41序列中的游离半胱氨酸上形成gp120/gp41复合体。此复合体可被用作抗原,因为他们可以模拟HIV-1病毒颗粒或病毒感染细胞表面病毒刺中的gp120/gp41复合体。
在另一个实施方案中,gp120序列中的游离半胱氨酸与细胞特异性结合半族、药物、免疫刺激性寡核苷酸(如,CpG)或免疫原性载体蛋白通过共价键连接。通过此方法将衍生的gp120定位于抗原提呈细胞(如树突细胞或巨噬细胞),可用于调节免疫反应的潜力和质量(如,TH1或TH2免疫反应)。用于本发明的细胞特异性半族包括任何可以连接到位于靶细胞(如白细胞)表面的且在非靶细胞(如肝或肌肉细胞)上没有的特异的配体结合位点任何的半族(如,配体或其片段)。一般而言,细胞特异性结合半族连接到与膜结合的细胞表面蛋白、碳水化合物、脂质、粘多糖、脂蛋白、抗原或受体上。因此,的细胞特异性结合半族的示例包括,例如,配体,如激素或细胞因子,激素或细胞因子的受体结合结构域,粘附因子和抗体。通常使用的适用于本发明的免疫原性载体包括白喉毒素、匙孔血蓝蛋白(KLH)、甲状腺球蛋白、牛血清白蛋白(BSA)和破伤风毒素。
B.gp120多肽的制备
1.合成技术
可以使用本领域公知的方法合成本发明的多肽,例如,完全的固相合成,部分固相合成,片段浓缩和经典的液相合成。参见Merrifield,J.Am.Chem.Soc.,85:2149(1963)。优选固相技术,其在例如JohnMorrow Stewart和Janis Dillaha Young,Solid Phase PeptideSyntheses(2nd Ed.,Pierce Chemicai Company,1984)中描述。在固相,典型地应用alpha氨基酸被防护的树脂从多肽的C末端开始合成。恰当的起始物质可以通过,例如,将所需的alpha氨基酸附着到氯甲基树脂,羟甲基树脂,或二苯甲基胺树脂而制备。自动多肽合成仪可以通过商业购到,也有预定制备多肽的服务。
2.重组技术
本发明的多肽也可以通过重组技术制备。gp120多核苷酸序列可以通过合成,从病毒RNA反转录的cDNA、前病毒DNA或克隆的gp120多核苷酸或HIV-1分离物,或从HIV-1分离物的另外克隆扩增(通过PCR、RT-PCR、循环扩增(RCA)或其他扩增方法)产生。如果手上有给定的gp120多聚核苷酸,则编码所需的gp120氨基酸序列的多聚核苷酸可以通过许多克隆和突变技术获得。参见,如,Sambrook,,J.,,Fritsch,,E.F.,,和Maniatis,,T.(1989)in Molecular Cloning:A LaboratoryManual,,Second Edition,,Cold Spring Harbor,,N.Y.。广泛应用的突变技术的例子包括定点突变(Kunkel等.,(1991)MethodsEnzymol.,204:125-139;Carter,P.,等,(1986)Nucl.AcidsRes.10:6487),盒式诱变(Wells,J.A.,等.,(1985)Gene 34:315)和限制性选择性突变(Wells,J.A.,等,(1986)Philos.Trans.R.Soc.,London Ser.A,317:415)。
在本发明的一个优选的实施方案中,gp120编码区的序列被用来指导设计一个编码所需gp120序列的多肽并可以整合到本发明载体中的合成的多聚核苷酸。构建合成基因的方法是本领域技术人员熟知的。参见,如Dennis,M.S.,Carter,P.和Lazarus,R.A.(1993)Proteins:Struct.Funct.Genet.,15:312-321。下面结合本发明的核酸、载体和宿主细胞更详细的描述了表达和纯化方法。
3.复合体和连接物
可以通过常用技术修饰本发明的gp120多肽以生产多肽复合物和连接物。包括一个或多个gp120多肽的二硫键连接的寡聚复合物可以通过,例如,将多肽混合到含有温和的还原试剂,如谷胱甘肽,二硫苏糖醇(DTT),β-巯基乙醇,和任选地,变性剂,如尿素或盐酸胍的溶液中制备。可以用透析除去还原试剂和任选的变性剂。二硫键在有空气存在的复性过程中形成,空气氧化还原的巯基集团。分子内的二硫键产生低聚体。如果溶液中仅含有一种类型的gp120多肽,形成的低聚体将含有该种。如果溶液中含有不同的gp120多肽或gp120多肽于其他多肽(如,gp41),形成的低聚体可含有多种。
作为选择的,本发明的含有一个或多个gp120多肽的低聚体复合物可以通过如,标准的双功能交叉连接试剂来制备。该试剂也可被用来生产gp120多肽与细胞特异性连接半族、药物、免疫刺激性寡核苷酸、或免疫原性载体蛋白的连接物。
对于其他应用,如以下描述的诊断方法,希望将可检测标志附着到一个或本发明的gp120多肽。适用于本发明的可检测标志包括通过分光镜的、光化学的、生物化学的、免疫化学的、电的、光的或化学的方法可以检测的任何组合物。例子包括与标记的链亲和素连接的用于染色的生物素、磁珠(如DynabeadsTM)、荧光染料(如荧光素、德克萨斯红、罗丹明、香豆素、嗪、绿色荧光蛋白等等,参见,例如MolecularProbes,Eugene,Oregon,USA)、放射标记(如,3H、125I、35S、14C、或32P)、酶(如辣根过氧化物酶、碱性磷酸酶和其他ELISA中常用的酶)以及如胶体金的比色标记(如具有高精确度的颗粒直径为40-80nm的分散绿光的金颗粒)或有色玻璃或塑料(如聚苯乙烯、聚丙烯、橡胶等)珠。讲述这些标记的应用的专利包括美国专利Nos.3817837;3850752;3939350;3996345;4277437;4275149和4366241.
编码具有稀有二硫化物结构的gp120多肽的分离多聚核苷酸、载体和宿主细胞
本发明还提供了编码本发明多肽的分离多聚核苷酸。相应的,本发明的多聚核苷酸包括编码gp120氨基酸序列的DNA或RNA部分。本发明的多聚核苷酸可用于本发明多肽的体内(即,在有机体内)或体外(如,在培养的细胞中)的重组产物。在特别的实施方案中,如下所述的,本发明的多聚核苷酸可用于免疫原性组合物,如DNA疫苗、重组病毒、或病毒衍生的疫苗(即,病毒颗粒成分)。另外,本发明的gp120多聚核苷酸可用于确定一个样品是否含有编码具有稀有的二硫化物的gp120多肽的多聚核苷酸的诊断方法中。
A.多聚核苷酸
在某些实施方案中,多聚核苷酸编码与选自下列序列的gp120的每一个V1,V2,V3和C4结构域具有至少大约80%、大约85%、大约90%、大约95%、或大约99%的同一性的gp120序列:SEQ ID NO:2,4,6,8,10,12,14,16,’18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48,50,52,54,56,58,60,62,64,66,68,70,72,74,76,78,80,82,84,86,88,90,92,94,96,98,100,102,104,106,108,110,112,114,116,118,120,122,124,126,128,130,132,134和136。在一个优选的实施方案中,多聚核苷酸包括选自下列序列的gp120核苷酸序列:SEQ BD NO:1,3,5,7,9,11,13,15,17,19,21,23,25,27,29,31,33,35,37,39,41,43,45,47,49,51,53,55,57,59,61,63,65,67,69,71,73,75,77,79,81,83,85,87,89,91,93,95,97,99,101,103,105,107,109,111,113,115,117,119,121,123,125,127,129,131,133,135或其亚序列,其中亚序列至少编码gp120的V1,V2,V3和C4结构域。上表1出示了序列ID号与来自上述的临床检测的gp120标本间的对应性。HIV-1的HXB-2株gp120序列是SEQ IN NO:137。
如上所述,被编码的gp120氨基酸序列可以是野生型序列或是变异序列。在gp120氨基酸序列是野生型序列时,编码该序列的核苷酸序列可以是野生型核苷酸序列或是一个含有一个或多个“沉默”突变的序列,该突变由于基因编码的简并性而不改变氨基酸序列的序列。
例如,如果试图将多聚核苷酸应用于表达被编码的多肽,则可以通过标准的突变技术导入沉默突变,以选择那些宿主细胞优选的密码子。可选择地,含有沉默突变的多聚核苷酸可以被设计并合成。更特别地,如本领域技术人员所理解的,密码子的应用是高度不随机的,具有种之间的不同。已表明密码子的应用方式与同功tRNA的相对丰度相关。在gp120的情况下,已表明密码子频率的改变将增加哺乳动物中gp120重组产物(Haas J等(1996)Curr Biol.6(3):315-24;Andre S.等(1998)J Virol.72(2):1497-503.)。天然gp120编码序列通常具有超过60%的A-T,而在哺乳动物系统高度表达的基因趋向于有大约60%的G-C。因此,当本发明的多聚核苷酸被用于在哺乳动物中表达本发明的多肽时,多聚核苷酸优选为优化的密码子,从而使密码子的频率更接近哺乳动物基因中的,更优选地,相对高表达的哺乳动物基因的密码子的频率。
本发明的密码子优化的多聚核苷酸典型地与未经优化的相应核苷酸序列相比大约有50%-80%的不同。因此,本发明的密码子优化的多聚核苷酸与相应未经优化的多聚核苷酸相比具有大约50%、大约60%、大约70%、大约80%或大约90%的序列同一性。
在一个优选的实施方案中,本发明的多聚核苷酸是适于在哺乳动物细胞中表达的优化密码子。特别感兴趣的是啮齿动物细胞(如小鼠、大鼠和仓鼠细胞)和灵长类细胞(如,猴和人细胞)。在一个优选的实施方案中,本发明的多聚核苷酸是适于在中国仓鼠卵巢(CHO)细胞表达的优化密码子。本发明的多聚核苷酸可以根据希望其所在的类种的任何基因进行密码子优化,但是密码子优化优选通过将密码子的频率改变为接近相对高的表达基因来进行。例如,本发明的多聚核苷酸可以具有接近那些免疫球蛋白的密码子频率。因此,例如,人的Ig Kappa和Mu保守区基因的密码子频率可以被确定,多聚核苷酸可以被加工为具有接近Ig Kappa和Mu保守区基因的相结合的密码子频率。简言之,这些基因的序列可以从GenBank或相似的数据库中下载。Ig Kappa C区被指定作为GenBank中的HUMIGKC3位置,Ig Mu的C区序列被指定作为HSIGMHCC位置。然后这些序列可以被翻译并确定密码子使用。可以整合密码子使用的信息并且计算整合的密码子频率。具有基本上与Ig基因的结合密码子频率相匹配的密码子频率的本发明的密码子优化的多聚核苷酸而后可以被很方便地通过合成产生。
在一些应用中,稳定此处描述的多聚核苷酸或生成被修饰后可以更好使其适应特殊应用的多聚核苷酸是有利的。为了此目的,本发明的多聚核苷酸可以含有硫代磷酸酯,磷酸三酯,甲基膦酸酯,短链烷基或环烷基内糖链或短链杂原子或杂环内糖(骨架)连接。最优选的是硫代磷酸酯以及那些具有CH2-NH-O-CH2,CH2-N(CH3)-O-CH2(已知为亚甲基(亚氨甲基)或MMI骨架)和CH2-O-N(CH3)-CH2,CH2-N(CH3)-N(CH3)-CH2和O-N(CH3)-CH2-CH骨架(其中磷酸二酯是O-P-O-CH2)。而且,优选的是具有吗啉代骨架结构的多聚核苷酸。Summerton,J.E.and Weller,D.D.,U.S.Pat.No.5034506。其他优选的实施方案使用了蛋白-核酸或多肽-核酸(PNA)骨架,其中多聚核苷酸的磷酸二酯骨架被聚酰胺骨架取代,碱基被直接或间接连接到聚酰胺骨架的氮杂原子上。P.E.Nielsen,M.Egholm,R.H.Berg,O.Buchardt,Science 1991,254,1497。本发明的多聚核苷酸可以含有烷基和卤素取代的糖半族和/或含有糖的类似物如以环丁基取代pentofuranosyl集团。在另一个优选的实施例中,多聚核苷酸可以包括至少一个修饰的碱基或“通用碱基”如次黄(嘌呤核)苷。如果需要,多聚核苷酸可以包括RNA分裂集团(cleaving group)、胆甾醇集团、受体集团、嵌入剂、用于提高多聚核苷酸药物代谢动力学特性的集团和/或用于提高多聚核苷酸药物动力学特性的集团。
本发明的多聚核苷酸还可以被修饰成含有任何可用于杂交分析的各种适合的标记。适合的标记包括上述那些适于标记本发明的gp120多肽的。荧光分子可以很方便地标记用于诊断方法的多聚核苷酸。可以被附着到多聚核苷酸上的荧光分子包括但不局限于,如荧光素、德克萨斯红、罗丹明、香豆素、嗪、绿色荧光蛋白。本领域技术人员可以理解与本发明的多聚核苷酸编码链互补或基本上互补的多聚核苷酸可被用于抑制本发明的多聚核苷酸的表达,其在研究或治疗中有意义。因此,本发明的核酸包括如“反义多聚核苷酸”,惯用语“编码本发明多肽的多聚核苷酸”也包括那些反义分子。反义多聚核苷酸可以是DNA或RNA,其分别用于研究或治疗的反义或RNA干涉(RNAi)的应用中。
本发明的多聚核苷酸可以通过合成、从克隆的gp120多聚核苷酸或HIV-1分离物扩增产生,或从HIV-1分离物获得的其它扩增而获得。如果有必要,可以应用任何克隆或突变技术改变获得的多聚核苷酸的核苷酸序列而达到所需的核苷序列。参见Sambrook,.J.,Fritsch,E.F.,and Maniatis,T.(1989)in Molecular Cloning:A LaboratoryManual,Second Edition,Cold Spring Harbor,N.Y.。
B.载体
本发明的多聚核苷酸可以被整合到载体上以便于在宿主细胞上增殖和/或表达。此载体典型地含有一个可以有效地在宿主细胞(如,大肠杆菌,中国仓鼠卵巢(CHO)细胞)中复制载体的复制序列(即,复制起点)以及编码一个选择性标记,如抗生素抗性基因的序列。转染到适当的宿主细胞后,载体可以不依赖于宿主细胞的基因组而独立地复制和发挥功能或者插入宿主基因组中。在其他事情中,载体的设计依赖于载体的用途和宿主细胞,本发明的用于特定应用和特定宿主细胞的载体设计在本领域技术人员的能力内。
如果载体是被用于表达多肽,则载体包括一个或多个可以有效和/或增强可操作地连接的多肽编码序列的表达的控制序列。在原核细胞中适于表达的控制序列例如包括,启动子序列,操纵子序列和核糖体结合点。在真核细胞中适于表达的控制序列包括启动子,增强子和转录终止序列(即,多聚腺苷酸信号)。本发明的表达载体可用于在体内表达本发明的多肽(如,在DNA或病毒衍生疫苗的应用中)或在体外(如,细胞培养)。
本发明的表达载体还可以包括其他序列,如,编码信号序列或可扩增基因的核苷酸序列。信号序列可以指导与其融合多肽从表达蛋白质的细胞分泌。在表达载体中,编码信号序列的核酸被连接到编码序列以保护编码序列的阅读框。另外,在载体中包含的补足所选的宿主细胞营养缺陷的基因可以对转染载体的宿主细胞进行选择。
对于将本发明的多聚核苷酸传送到细胞或有机体,随后进行编码蛋白的表达,病毒载体是非常有意义的。作为将多聚核苷酸传送到有机体以减轻病理状态,即“基因治疗”中的传送方法,病毒载体已经被广泛研究了。对于基因治疗步骤的总结,参见,Anderson,Science(1992)256:808-813;Nabel和Felgner(1993)TIBTECH 11:211-217;Mitani和Caskey(1993)TIBTECH 11:162-166;Mulligan(1993)Science,926-932;Dillon(1993)TIBTECH 11:167-175;Miller(1992)Nature 357:455-460;Van Brunt(1988)Biotechnology 6(10):1149-1154;Vigne(1995)Restorative Neurology andNeuroscience 8:35-36;Kremer和Perricaudet(1995)BritishMedical Bulletin 51(1)31-44;Haddada等(1995)in Current Topicsin Microbiology and Immunology,Doerfler andBhm(eds)Springer-Verlag,Heidelberg Germany;和Yu等,(1994)GeneTherapy,1:13-26。
广泛应用的病毒载体系统包括,但并不局限于腺病毒,腺相关病毒,痘苗病毒,金丝雀痘病毒,疱疹病毒,和各种逆转录病毒表达系统。腺病毒载体的应用对本领域技术人员是熟知的,其详细记载于如WO96/25507。特别优选的腺病毒载体在Wills等(1994)Hum.GeneTherap.5:1079-1088中描述了。适用于本发明的腺病毒载体也可以买到。例如,Clontech卖的Adeno-XTMTet-OffTM基因表达系统提供了将可诱导的异源基因导入大多数宿主细胞的有效的手段。
基于腺相关病毒(AAV)载体用于将靶基因转染细胞,如体外生产多聚核苷酸和多肽,在体和离体的基因治疗方法,如West等(1987)Virology 160:38-47;Carter等(1989)U.S.Patent No.4797368;Carter等WO 93/24641(1993);Kotin(1994)Human Gene Therapy5:793-801;Muzyczka(1994)J.Clin.Invst.94:1351;Lebkowski,U.S.Pat.No.5173414;Tratschin等(1985)Mol.Cell.Biol.5(11):3251-3260;Tratschin,等(1984)Mol.Cell.Biol.,4:2072-2081;Hermonat and Muzyczka(1984)Proc.Natl.Acad.Sci.USA,81:6466-6470;McLaughlin等(1988)and Samulski等(1989)J.Virol.,63:03822-3828中描述的。可以被rAAV转染的细胞系包括Lebkowski等(1988)Mol.Cell.Biol.,8:3988-3996中所描述的那些。
广泛应用的腺病毒载体包括鼠类白血病病毒(MuLV)、长臂猿白血病病毒(GaLV),猿免疫缺陷病毒(SIV),人免疫缺陷病毒(HIV),α病毒及其组合物(参见,如Buchscher等(1992)J.Virol.66(5)2731-2739;Johann等(1992)J.Virol.66(5):1635-1640(1992);Sommerfelt等,(1990)Virol.176:58-59;Wilson等(1989)J.Virol.63:2374-2378;Miller等,J.Virol.65:2220-2224(1991);Wong-Staal等,PCT/US94/05700,and Rosenburg and Fauci(1993)in Fundamental Immunology,Third Edition Paul(ed)Raven Press,Ltd.,New York and the references therein,and Yu等(1994)GeneTherapy,supra;U.S.Patent 6,008,535等)。其他适合的病毒载体包括但不局限于单纯疱疹病毒(HSV),乳头瘤病毒,EB病毒(EBV),和慢病毒的载体。
在一个实施例中,本发明的载体是可作为DNA疫苗和重组病毒载体的双功能质粒。直接将纯化的病毒载体DNA注射到被治疗者,即,用作DNA疫苗,可诱发对编码多肽的免疫反应。载体还可制备用于在病毒衍生的疫苗中使用的活的重组病毒。此载体包括编码本发明多肽的核苷酸,其被可操纵地连接到两个不同的启动子:一个动物启动子(用于DNA疫苗中的载体)和一个病毒启动子(用于病毒衍生的疫苗中)。
通过在方便的限制酶切点连接所需的成分产生本发明的载体。如果不存在此酶切点,则通过标准的突变技术导入合适的位点(如,定点突变或盒式诱变)或根据实际应用的方便性使用合成的寡核苷酸适配体或连接子。
C.宿主细胞
本发明还提供了含有本发明载体的宿主细胞。存在多种用于增殖和/或表达载体的宿主细胞。例子包括原核细胞(如大肠杆菌,杆菌属,假单胞菌和其他细菌),酵母或其他真菌细胞(包括酿酒酵母,甲醇营养性酵母),昆虫细胞,植物细胞,噬菌体,以及高级真核细胞,包括哺乳动物细胞(如中国仓鼠卵巢细胞),和,特别地,人类细胞(如人胚肾脏细胞)。本发明的宿主细胞包括培养的细胞和存在于活的有机体的细胞,如被导入DNA疫苗或病毒载体的转基因植物或动物或细胞。
本发明的载体可以通过任何方便的方法被导入宿主细胞,其依赖于所应用的载体-宿主细胞系统。一般而言,载体通过转染(也叫转化)被导入宿主细胞或通过感染携带载体的病毒。如果宿主细胞是原核细胞(或其他具有细胞壁的细胞),方便的转染方法包括钙处理方法,如Cohen,等(1972)Proc.Natl.Acad.Sci.,USA,69:2110-14中所描述的。如果原核细胞被用作宿主而载体是嗜菌体载体,则可通过感染将载体导入宿主细胞。可以应用聚乙烯乙二醇转染酵母细胞,如Hinnen(1978)Proc.Natl.Acad.Sci,USA,75:1929-33中所述。可以应用Graham,等(1978)Virology,52:546 and by Gorman,等(1990)DNA and Prot.Eng.Tech.,2:3-10中描述的磷酸钙沉淀的方法方便地转染哺乳动物细胞。可是,其它已知的将DNA导入宿主细胞的方法,如核注射,电穿孔和原生质融合也可用于本发明。
本发明包括向体内以及体外细胞,如培养的细胞中导入本发明的载体。用于将载体导入活的有机体细胞的技术是已知的,将在下面关于本发明的免疫源性组合物的应用中具体描述。在特别的实施例中,本发明的载体DNA或病毒衍生的疫苗中的形式被导入被治疗者。
重组的制备方法
被转染了表达载体的宿主细胞可以被用于表达本发明多聚核苷酸编码的多肽。表达需要在适于细胞生长和表达的条件下培养细胞,从溶解物中回收表达的多肽,如果多肽被分泌则可以从培养基中回收。特别地,培养基含有适合于宿主细胞的营养物和生长因子。在多数情况下,营养物和生长因子是公知的或本领域技术人员根据经验可确定的。例如,哺乳动物宿主细胞适合的培养条件在Mammalian CellCulture(Mather ed.,Plenum Press 1984)和Barnes and Sato(1980)Cell 22:649中详细描述了。
另外,培养条件应当适合细胞间的转录、翻译和蛋白质的运输。影响这些过程的因子是公知的,其包括,例如DNA/RNA拷贝数;稳定DNA的因子;培养基中的营养物,补充物和转录诱导物或抑制物;培养的温度,pH和渗透度;以及细胞的密度。调整这些因子以促进在特定载体宿主细胞系统内的表达是本领域技术人员能做到的。使体外哺乳动物细胞培养的产量最大化的原则和实践方法,例如,可参考Mammalian Cell Biotechnology:a Practical Approach(Butler ed.,IRL Press(1991)。
任何用于大规模或小规模生产蛋白质的公知技术都可以用在本发明的多肽表达中。其包括但不局限于,应用摇瓶方法,液床生物反应器,滚瓶培养系统,和搅拌罐生物反应器系统。细胞培养可以在分批式操作,流加式操作或连续式操作下进行。
如上所述的回收产生的蛋白质的方法是公知的,其依所用的表达系统的不同而不同。包括信号序列的多肽可以被从培养基或外周血桨中回收。多肽还可以在细胞内被表达,从细胞溶解液中回收。
可以使用任何可以从一个或多个宿主细胞或培养基成分中分离多肽的方法,从培养基或细胞溶解液中纯化表达的多肽。典型地,将多肽从可干扰多肽应用的宿主细胞和/或培养基成分中分离出来。第一步,通常将培养基或细胞溶解物离心或过滤以除去细胞残渣。然后将上清浓缩或稀释到所需的容量或渗滤到适合的缓冲液以利于下一步的纯化。
然后可用熟知的技术将多肽纯化。所选的技术依据表达的多肽的特性的不同而不同。例如,如果表达的多肽是含有附加表位或其他亲和结构域的融合蛋白,则典型的纯化包括使用含有关联的结合物的亲和柱。例如,与绿色荧光蛋白,红细胞凝聚素,或FLAG附加表位或六组氨酸或相似的金属亲和簇融合的多肽可以通过亲和柱的分离被纯化。
免疫原性的组合物
A.免疫原性的组合物的类型
本发明的免疫原性的组合物包括本发明的分离多肽或分离多聚核苷酸或两者。本发明的分离gp120多肽存在于免疫原性组合物中,当向被治疗者投药适当剂量时,所含的gp120多肽的量足以诱导抗gp120的免疫反应发生。本发明的分离gp120多聚核苷酸存在于免疫原性组合物中,当向被治疗者投药适当剂量时,所含的gp120多聚核苷酸免疫的量可以导致其编码的gp120多肽的表达,该多肽可刺激抗gp120的免疫反应。
在一个优选的实施例中,免疫原性组合物是“多价的”,其提供了至少两个不同的抗原gp120序列。因此,以多肽为基础的组合物可以含有包括衍生于至少两个不同HIV分离物的gp120序列的一个或多个多肽。以多聚核苷酸为基础的组合物可以含有一个或多个编码衍生于至少两个不同HIV分离物的gp120序列的多聚核苷酸。可选择地,本发明的免疫原性组合物可以含有至少一个包括衍生于一个HIV分离物的gp120序列的多肽和至少一个编码衍生于不同HIV分离物的gp120序列的多聚核苷酸。本实施例的变形可以提供所需的很多不同的抗原gp120序列,如,3,4,5,6,7,8,9,10,20,30,40,50,或100或更多不同的gp120序列。
1.含有多肽的免疫原性组合物
本发明提供了含有本发明多肽的免疫原性组合物。组合物可选择地含有其它成分,例如,包括储存溶液,如适合的缓冲液,例如,生理的缓冲液。在一个优选的实施例,其它的成分是药学上可接受的载体,如Remington’s Pharmaceutical Sciences(1980)16th editions,Osol,ed.,1980中所描述的。
免疫原性组合物可以包括一个或多个游离存在(即,未连接到其它半族)或共价结合到细胞特异性结合半族、免疫刺激性寡核苷酸、或免疫原性载体蛋白的本发明的多肽。
在一个实施例中,本发明的免疫原性组合物包括表达本发明多肽的细胞、含有多肽的细胞溶解物或其碎片,如细胞膜碎片。
在另一个实施例中,免疫原性组合物包括表现本发明的一个或多个多肽的病毒颗粒和/或病毒感染的细胞。用经改造的病毒颗粒和/或感染的细胞免疫被治疗者受体是本领域公知的,用于免疫的组合物通常被称为“病毒衍生的疫苗”。病毒衍生的疫苗是有利的,这是因为病毒感染成分能够促进激活B淋巴细胞,辅助T淋巴细胞,杀伤T淋巴细胞的强烈的免疫反应。很多病毒种可用于生产用于病毒原性疫苗的重组病毒。例子包括病毒衍生的疫苗(Moss等人的国际专利公开号WO87/06262,Oct.22,1987,.;Cooney等,Proc.Natl.Acad.Sci.USA 90:1882-6(1993);Graham等,J.Infect.Dis.166:244-52(1992);McElrath等,J.Infect.Dis.169:41-7(1994))和金丝雀痘病毒(Pialoux et al.,AIDS Res.Hum.Retroviruses 11:373-81(1995),erratum in AIDS Res.Hum.Retroviruses 11:875(1995);Andersson等,J.Infect.Dis.174:977-85(1996);Frieset al.,Vaccine 14:428-34(1996);Gonczol et al.,Vaccine 13:1080-5(1995)),也可以使用缺陷腺病毒或腺病毒制备病毒衍生的疫苗(Gilardi-Hebenstreit等,J.Gen.Virol.71:2425-31(1990);Prevec等,J.Infect.Dis.161:27-30(1990);Lubeck等,Proc.Natl.Acad.Sci.USA86:6763-7(1989);Xiang等,Virology 219:220-7(1996))。其它可以被改造而产生用于疫苗的重组病毒包括被包裹在双嗜性宿主的细胞内的腺病毒(参见,Miller,Human Gene Ther.1:5-14(1990);Ausubel et al.,Current Protocols in MolecularBiology,9),和减毒的或缺陷的DNA病毒,如但不局限于单纯疱疹病毒(HSV)(参见,Kaplitt et al.,Molec.Cell.Neurosci.2:320-330(1991),乳头瘤病毒,EB病毒(EBV),腺相关病毒(AAV)(参见,Samulskiet al.,J.Virol.61:3096-3101(1987);Samulski et al.,J.Virol.63:3822-3828(1989)),等等。
适用于本发明的药学上可接受的载体在使用的剂量上,对细胞、组织或被治疗者被治疗者是无毒性的,其可包括一个缓冲液(如磷酸盐缓冲液,柠檬酸盐缓冲液和其它有机酸制得的缓冲液),一个抗氧化物(如抗坏血酸),一个低分子量(小于10个残基)的多肽,一个多肽(如血清球蛋白,明胶,或免疫球蛋白),一个亲水聚合体(如聚乙烯吡咯烷酮),一个氨基酸(如甘氨酸,谷氨酸,天冬氨酸,精氨酸和/或赖氨酸),一个单糖,一个二糖和/或其他碳水化合物(包括葡萄糖,甘露糖和糊精),一个螯合剂(如EDTA),一个糖醇(如甘露醇或山梨醇),一个盐形成的抗衡离子(如钠),和/或阴离子表面活性剂(如TweenTM,PluronicsTM和PEG)。在一个实施例中,药学上可接受的载体是一个pH缓冲液的水溶液。
优选的是实施例包括持续释放的组合物。一个持续释放的组合物的例子具有固体疏水聚合体的半通透性基质,多肽被附着于其上或包裹在其中。合适的聚合体的例子包括聚酯,水凝胶,聚交酯,L谷氨酸的共聚体,和T-乙烷基-L-谷氨酸盐,不能降解的乙烯-乙烯基乙酸,可降解的乳酸-乙醇酸共聚体和聚-D-(-)-3-羟基丁酸。这些基质已成形的物质存在,如膜或微囊。
持续释放的组合物的例子包括典型地通过ε-氨基基团附着到聚亚烃基乙二醇(如聚乙烯乙二醇[PEG])的多肽。将PEG附着到蛋白质上是体内延长半衰期公知的方法(参见Abuchowski,J.,et al.(1977)J.Biol.Chem.252:3582-86)。如果“长效的”(pegylation)变异保留了所需的功能,则可以使用任何“长效”的方法。
在另一个实施例中,持续释放的组合物包括脂质体包裹的多肽。脂质体是由各种类型的脂质,磷脂,和/或表面活性剂组成的小囊。这些成分典型地形成一个双层的结构,象生物膜的脂质构造。含有多肽的脂质体通过公知的方法制备,如在Epstein,et al.(1985)PNAS USA82:3688-92,and Hwang,et al.,(1980)PNAS USA,77:4030-34中所描述的。通常此种制备中的脂质体是小的(大约200-800埃)单薄层的,其中脂质含量大约大于30mol。百分比胆固醇,特定的百分比可以被调节,以提供最佳的治疗。有用的脂质体可以通过使用包括例如,卵磷脂、胆固醇和PEG衍生的磷脂酰乙醇胺(PEG-PE)的脂质组合物,通过反相蒸发的方法生成。如果需要,可以通过特定孔径尺寸的过滤器挤压脂质体,以生成特定的直径。
本发明的组合物还包括吸附到膜上的一个多肽,例如硅橡胶膜,其可被植入,如国际公开No.Wo91/04014所述。
本发明的免疫原性组合物还可以以任何标准的形式储存,包括,如水溶液或冻干的糕。当注射于被治疗者被治疗者时,此组合物典型地是灭菌的。水溶液的灭菌可通过用无菌过滤膜过滤来实现。如果组合物以冻干形式储存,则可在冻干和重建之前或后过滤组合物。
2.含多聚核苷酸的免疫原性组合物
本发明提供了含编码本发明多肽的分离多聚核苷酸的免疫原性组合物。最优地此组合物含有其他成分,如,储存溶液,如合适的缓冲液,如,生理性缓冲液。在一个优选的实施例中,其他成分是上述药学上可接受的载体。
用多肽抗原进行传统免疫的一个改变包括将编码抗原的多聚核苷酸在体内导入被治疗者的组织以使被治疗者的组织细胞表达抗原。用于免疫被治疗者的以多聚核苷酸为基础的组合物被定义为“DNA疫苗”或“核酸疫苗”。DNA疫苗在国际专利公开号WO95/20660和国际专利公开号WO93/19183中被描述。直接注射编码病毒蛋白质的DNA以诱导免疫反应的能力已在多个实验系统中被描述(Conry et al.,CancerRes.,54:1164-1168(1994);Cox et al.,Virol,67:5664-5667(1993);Davis et al.,Hum.Mole.Genet.,2:1847-1851(1993);Sedegah et al.,Proc.Natl.Acad.Sci.,91:9866-9870(1994);Montgomery et al.,DNA Cell Bio.,12:777-783(1993);Ulmeret al.,Science,259:1745-1749(1993);Wang et al.,Proc.Natl.Acad.Sci.,90:4156-4160(1993);Xiang et al.,Virology,199:132-140(1994))。在中性流感病毒中评估此策略的研究中使用了包膜和内病毒蛋白质以诱导产生抗体,但是特别地把焦点放在病毒红血球凝聚素蛋白质(HA)(Fynan et al.,DNA Cell.Biol.,12:785-789(1993A);Fynan et al.,Proc.Natl.Acad.Sci.,90:11478-11482(1993B);Robinson etal.,Vaccine,1l:957,(1993);Webster et al.,Vaccine,12:1495-1498(1994))。通过直接将编码HIV包膜蛋白的DNA导入以诱导防御性免疫反应既可产生细胞介导又可产生体液反应,类似于从活病毒所获的反应那样(Raz et al.,Proc.Natl.Acad.Sci.,91:9519-9523(1994);Ulmer,1993,supra;Wang,1993,supra;Xiang,1994,supra)。另外,在小鼠上有报道对编码核蛋白的DNA的免疫反应可以持续动物终生(Yankauckas et al.,DNA Cell Biol.,12:771-776(1993))。DNA疫苗可以被设计成刺激不同的免疫反应。如,最好通过蛋白抗原的细胞内表达来刺激组织相容性抗原I(MHC-I)的反应。为了达到此目的,编码gp120信号序列的序列被删除并被编码起始甲硫氨酸的密码子取代。没有信号序列的gp120序列在细胞内游离的核糖体上被合成,不需要N连接的碳水化物,使细胞内蛋白水解的过程,能刺激MHC-I限定的免疫反应。MHC-I反应被认为在促进CD8阳性T细胞介导的毒性T细胞反应中特别有效。相对的,当编码信号序列的gp120基因在哺乳动物细胞中表达时,信号序列指导在与膜结合的核糖体上合成并运输到“分泌路径”,其中被运到细胞表面或细胞外间隙的蛋白质得到一系列的翻译后修饰(如糖基化)并被提呈到与主要组织相容性蛋白II(MHC-II)相关的免疫系统。与MHC-II抗原相关的蛋白抗原在促进抗体反应和CD-4介导的T细胞反应中特别有效,但在刺激CD8依赖的免疫反应(如细胞毒性T淋巴细胞【CTLs】)中无效。
如本领域中所公知的,很多因子能够影响抗原基因表达的效率和/或DNA疫苗的免疫原性。这些因子的例子包括载体,用于启动抗原基因表达的启动子,和质粒中插入基因的稳定性。根据其来源,启动子的组织特异性和启动mRNA的有效性不同(Xiang et al.,Virology,209:564-579(1994);Chapman et al.,Nucle.Acids.Res.,19:3979-3986(1991))。哺乳动物系统中很多DNA疫苗依赖于来自细胞巨化病毒(CMV)的病毒启动子。他们在多数哺乳动物种的肌肉和皮肤的孵育中具有很好的有效性。
对于药学应用,本发明的多聚核苷酸以适合特定指示的配方表示。Bennett等在美国专利No.6001651中描述了一些适用于寡核苷酸治疗的药学组合物和配方以及投药这些寡核苷酸的方法。在一个优选的实施例中,本发明的治疗组合物包括结合质脂的多聚核苷酸,如上所述。
包括多聚核苷酸的组合物可以以任何形式被储存,包括,如水溶液或冻干糕。当投药到细胞或被治疗者被治疗者时,典型地这些组合物被消毒。水溶液的消毒通常通过无菌过滤膜过滤完成。如果组合物以冻干形式储存,则可在冻干和重建之前或后过滤组合物。
3.其他组合物
除了上述组合物之外,本发明的免疫原性组合物可以包括一个或多个佐剂。佐剂的例子包括但不局限于,完全Freund佐剂,不完全Freund佐剂,皂角苷,矿物质凝胶如氢氧化铝,表面活性物质如溶血卵磷脂,聚丙二醇与环氧乙烷的加聚物(聚醚)多羟基化合物,聚阴离子,多肽,油酯或碳氢化合物乳剂,匙孔血蓝蛋白,二硝基酚,和BCG(Calmette-Guerin杆菌)和小的棒状杆菌。在近年,描述了一组新的佐剂,免疫刺激性寡核苷酸。他们是小的(大约15-30mer)化学合成的富含鸟嘌呤和胞嘧啶(富含GC)的寡核苷酸。在一些例子中(如,特别是抗原如B型肝炎表面抗原),这些寡核苷酸可以简单地与病毒抗原混合以具有免疫刺激作用。在其他例子中(如gp120),通过将寡核苷酸化学地结合到蛋白质以实现高活性。本申请描述的gp120分子特别适合用于与寡核苷酸化学结合的不配对半胱氨酸的免疫刺激性寡核苷酸衍生。佐剂的选择依赖于被免疫的被治疗者。优选地,应用药学上可接受的佐剂。用于人的优选的佐剂是铝(铝胶)。
其他抗原,如其他HIV-1多肽(如gp41)可以被包含在本发明的免疫原性组合物中。
免疫原性组合物可以包括其他可增强对本发明的多肽的抗gp120免疫反应或提供其他效果的多肽。例如,在一个特别的实施例中,在本发明的免疫原性组合物中可有利的含有一个或多个细胞因子,如干扰素或白细胞介素。
在一个优选的实施例中,包括本发明的分离多肽的组合物还可以包含有助于多聚核苷酸进入细胞的成分。有助于向细胞内传送多聚核苷酸的是公知的,包括,例如,脂质,脂质体,水-油分散剂,聚乙烯亚胺和树枝状结晶,这些的任何一个多可用于本发明的组合物。其中质脂是最常用的成分,任何存在的质脂或质脂配方均可用于本发明的多聚核苷酸。典型地,阳离子质脂优选。优选的阳离子质脂包括N-[1-(2,3-二油基氧)丙基]-N,N,N-氯化三甲基铵(DOTMA),二油酰基磷酸脂酰乙醇胺(dioleoyl phosphotidylethanolamine)(DOPE)和/或二油酰磷脂酰胆碱(dioleoyl phosphatidylcholine)(DOPC)。如上所述的多肽一样,多聚核苷酸也可以被包被在脂质体内。
在其他实施方案中,多聚核苷酸可以与树枝状结晶形成复合物,其可被用于细胞转化。树枝状结晶聚阳离子是三维的,高序列的寡聚体和/或多聚体的复合物,典型地在一个核心分子或在设计的启始子(initiator)中通过加入寡聚体和/或多聚体的重复反映序列而形成并提供肯定改变的较外层的表面。适合的树枝状结晶包括但不局限于,″星爆式″树枝状结晶和多种树枝状结晶聚阳离子。制备和应用树枝状结晶将多聚核苷酸在体内导入细胞的方法是本领域技术人员熟知的,并有详细描述,如PCT/US83/02052 and U.S.Patent Nos.4507466;4558120;4568737;4587329;4631337;4694064;4713975;4737550;4871779;4857599和5661025。
B.免疫原性组合物的应用
本发明的免疫原性组合物可被用于在动物体内产生gp120特异性免疫反应。可通过任何适当的给药途径将本发明的免疫原性组合物给动物,如下详细描述的。
在一个实施方案中,给动物免疫原性组合物以产生抗gp120抗体,如用于HIV研究的抗体。通常地,动物是典型的用于产生抗体。优选哺乳动物(如,啮齿类,兔子,山羊,绵羊等)。
通过将抗原注射(如皮下或肌肉注射)入合适的动物(如小鼠或兔子)产生多克隆抗体。然后从动物的血液样品中回收抗体。用于生成多克隆抗体的技术在本领域本广泛描述(如Methods of Enzymology,″Production of Antisera With Small Doses of Immunogen:MultipleIntradermal Injections″,Langone,et al.eds.(Acad.Press,1981)).然后进一步纯化动物产生的多克隆抗体,例如,通过将多肽连接到基质上而将抗体洗脱下来来回收抗体。本领域技术人员知道多种标准的方法可用多克隆抗体,以及单克隆抗体的纯化和/或浓缩,参见,如Coligan,et al.(1991)Unit 9,Current Protocols inImmunology,Wiley Interscience)。
在很多应用中,优选抗gp120单克隆抗体。用于制备杂交瘤分泌的mAbs的方法是公知的(Kohler and Milstein(1975)Nature,256:495)。简言之,如Kohler和Milstein所描述的,该技术包括从5个肿瘤病人的局部淋巴结分离淋巴细胞,收集细胞,使细胞与SHFP-1融合。筛选杂交瘤以制备结合到肿瘤细胞系上的抗体。可使用常规筛选技术(如酶联免疫吸附分析,或ELISA)以确定感兴趣的mAb的初级反应来完成对mAb’s的特异性。
可以选择地,本发明的免疫原性组合物还可以被用作疫苗投药与人体。特别地,可以将组合物投药给未感染HIV-1的个体以降低感染的风险,或预防感染(HIV-1感染预防)。如健康的专业人员,警察,和消防人员等个体可以从预防性给药本发明的疫苗而获益。组合物还可以被投药到已经感染HIV-1的个体,但其仍然可以产生免疫反应(详见,Salk,Nature 327:473-476(1987);and Salk et al.,Science195:834-847(1977))。所谓的“治疗疫苗”可以减轻已经存在的感染(例如,可以通过提高机体状态或减轻或防止疾病进展)和/或提供抗其他HIV-1株感染的预防。
1.含有多肽的免疫原性组合物
以多肽为基础的免疫原性组合物可以通过注射很方便地投药(如,皮下,皮内,肌肉内,腹腔内,静脉内等等),可是还可以通过导管或其他外科管子投药。可选择的途径包括口服(片剂等)和吸入(如应用商供的用于液体配方或冻干或气雾配方的喷雾器)。还可以通过微球,脂质体,免疫刺激复合物(ISCOMs),或微粒传送系统或持续释放的配方将多肽组合物导入适合的组织(如血液)。
免疫原性组合物中投药的gp120的免疫剂量取决于特定组合物的特性,如,特定配方的免疫原性,投药路径,免疫性配方,被治疗者的状态等等,对于特定条件的合适剂量的决定是本领域技术人员所知道的。一般而言,优选每次投药300ug的gp120多肽,尽管优选的剂量范围可以是每次投药10ug-1mg,但是也可以使用超过这个范围的剂量,这取决于特定的配方,给药途径(如肌肉相对于皮下)和/或免疫配方。在一个连续的接种中可以使用不同的剂量。因此,实践者在初次接种时可以使用相对大剂量的gp120多肽,然后用相对小剂量的gp120多肽支持。
2.含有多聚核苷酸的免疫原性组合物
本发明的以多聚核苷酸为基础的免疫原性组合物可以被用于在被治疗者体内表达编码的多肽,从而诱发对所编码多肽的免疫反应。Benvenisty,N.,and Reshef,L.[PNAS 83,95519555,(1986)表明通过CaPO4-沉淀将导入小鼠腹腔(i.p.),静脉内(i.v.),肌肉内(i.m.)的DNA可以表达。在小鼠内i.m.注射DNA表达载体导致了肌肉细胞摄取DNA和表达DNA所编码的蛋白质的表达。质粒被保持游离而不被复制。继而,在大鼠,鱼和猴的骨骼肌以及大鼠的心肌的肌肉i.m.注射后,可观察到持续表达。WO90/11092(Oct.4,1990)描述了裸多聚核苷酸用于接种脊柱动物的应用。
向动物导入多聚核苷酸有多种方法,选择向动物导入特定的多聚核苷酸的恰当的方法是本领域技术人员知道的。例如,向小鼠的皮肤导入编码牛生长激素(BHG)的DNA包被的金微粒表明显示在小鼠中诱导抗BHG抗体。应用注射器向活动物的皮肤,肌肉,脂肪和乳房组织转染。小鼠内导致克隆的转基因系统表达的DNA:阳离子脂质体复合物的静脉注射被Zhu et al.,[Science 261:209-211(Jul.9,1993)]报导。Ulmer et al.,[Science 259:1745-1749,(1993)报导报导了通过肌肉注射编码流感病毒蛋白质的DNA导致抗流感感染的异源防护。WO93/17706描述了接种动物抗病毒的方法,其中载体颗粒被基因构件包被,被包被的颗粒被加速到细胞内。应用“基因枪”的质粒高速接种增强了小鼠的免疫反应(Fynan,1993B,supra;Eisenbraun et al.,DNA Cell Biol.,12:791-797(1993)),估计是因为DNA转染的更有效性和树突细胞的更有效的抗原防护。本发明的多聚核苷酸还可以通过本领域的其他方法导入被治疗者,如,转染,电穿孔,微注射,转导,细胞融合,DEAE右旋糖苷,磷酸钙沉淀,脂质体转染(脂质体融合)或DNA载体运输(见,如Wuetal.,J.Biol.Chem.267:963-967(1992);Wu and Wu,J.Biol.Chem.263:14621-14624(1988);Hartmut et al.,Canadian PatentApplication No.2012311,filed Mar.15,1990)。
免疫原性组合物中gp120多聚核苷酸接种的剂量取决于特定组合物的特性,如特定配方的免疫原性,投药途径,免疫配方,被治疗者的状态等等,决定用于特定环境的适合的剂量是本领域技术人员知道的。一般而言,优选每次投药大约1-大约100mg的gp120多肽。在一个连续的接种中可以使用不同的剂量。因此,实践者在初次接种时可以使用相对大的剂量,然后用相对小剂量的gp120的多聚核苷酸支持。
3.免疫配方
gp120特异性免疫反应可以通过使用本发明的免疫原性组合物一次或多次接种被治疗者实现。第一次接种称为“初次接种”,随后的接种称为“支持接种”。通常支持接种可以加强免疫反应,优选的免疫配方包括至少一次支持接种。以上描述的任何类型的免疫组合物多可以被用于初次或支持接种。因此,例如本发明含有多聚核苷酸的免疫原性组合物(如或病毒衍生的疫苗)可被用于初次免疫,随后用含有本发明多肽的免疫原性组合物进行支持免疫,或反之亦然。另外,初次免疫和一次或多次支持免疫可以使用相同的和/或不同的gp120抗原序列。
在一个示范性实施方案中,合适的免疫配方包括应用本发明的一个或多个免疫原性组合物的至少三次分别接种,第二次接种超过大约第一次注射后两周,优选三到八周,最优选四周投药。通常,第三次接种在第二次接种之后的几个月进行,优选在第一次接种后的大约5个月以上,更优选在第一次接种后的6个月到2年,更优选在第一次接种后的8个月到1年。也期望超过三次以上的接种以增强被治疗者的“免疫记忆”。见Anderson et al.,J.Infectious Diseases 160(6):960-969(Dec.1989)。
可以通过在免疫过程中提取被治疗者血清液体分析抗体滴度来确定选择适当的接种的参数,如,配方,剂量,方法等等。作为选择地,可用传统的方法监测T细胞数。另外,为了所需的效果可以监测被治疗者的临床状况,如预防HIV-1感染或发展成AIDS,改善疾病状态(如,降低病毒量),或降低未感染伴侣的传染机会。如果这些监控显示免疫不理想,可以通过额外剂量的免疫原性组合物巩固被治疗者,免疫参数可以所希望的增强免疫反应的方式修改。因此,例如,可以增加gp120多肽或多聚核苷酸和/或增加佐剂的剂量,gp120多肽可以被结合或复合到免疫原性载体蛋白上,或改变给药途径。
诊断方法
A.检测具有稀有的二硫化物结构的gD120多肽的特异性抗体
本发明提供了确定被治疗者是否产生本发明的gp120多肽特异性抗体的诊断方法。该方法包括使来自被治疗者的生物样品与感兴趣的gp120多肽接触并确定样品是否含有特异性结合到gp120多肽的抗体。所用样品可以包括含有抗体的任何组织,但最方便的是血液或血液成份(如血清或血浆)。
可以应用任何一种熟知的免疫分析方法检测和/或定量样品中的抗gp120抗体(见美国专利4366241;4376110;4517288和4837168)。作为免疫分析方法的概述,见Methods in Cell Biology Volume 37:Antibodies in Cell Biology,Asai,ed.Academic Press,Inc.NewYork(1993);Basic and Clinical Immunology 7th Edition,Stites& Terr,eds.(1991)。
在一个标准的固相方式中,感兴趣的gp120多肽可以被附着到固相上作为吸附剂固定样品中任何gp120多肽的特异性抗体。然后被连接的抗体可以通过简单的洗脱步骤从样品游离的抗体分离出来。
典型地免疫分析应用标记试剂特异地结合,并标记gp120多肽及样品中的任何gp120多肽的特异性抗体结合形成的复合物。可以使用任何适宜的标记系统,无论是直接的还是间接的。例如,检测被治疗者的种的特异性抗体可以被用来标记任何结合到固相的抗体。其他可以特异的结合免疫球蛋白保守结构域的多肽,如多肽A或多肽G也可以被用作标记试剂。这些多肽通常是链球菌细胞壁的成分。它们与许多种的免疫球蛋白保守结构域具有强的非免疫活性。(见,Kronval,et al.(1973)J.Immunol.,111:1401-1406,and Akerstrom(1985)J.Immunol.,135:2589-2542)。合适的标记包括那些上述的标记本发明gp120多肽的标记。
根据本领域技术人员熟知的标准方法对本发明的分析打分(阳性或阴性或定量gp120抗体)。特定的打分方法取决于分析方式和选择的标记。例如,Wsetern blot分析可以通过肉眼可见的酶标产生的有色物进行打分。在正确的分子量的位置的清晰可见的有色带或点表明阳性结果,无清晰可见的有色带或点表明阴性结果。带或点的强度可以提供对gp120抗体浓度的定量分析。
在本发明的一个优选的实施方案中,本发明的免疫分析方法通过微电机械系统(MEMS)实现。MEMS是整合到硅上将机械,光和流控器件与电子学结合的微显微结构,以允许对感兴趣的分析进行监测。适于本发明的MEMS设备的例子是Protiveris’多悬臂阵列。这些阵列是以特定设计的硅胶多悬臂的化学机械刺激和而后的多悬臂偏斜的光学检测为基础的。当一侧被包被蛋白,抗体,抗原或DNA片段,当暴露于含有互补分子的溶液时,多悬臂将倾斜。这种倾斜是由于结合时发生的表面能量改变引起的。完全(偏斜)程度的光学检测使得可以测量结合到多悬臂的互补分子的量。
B.具有稀有二硫化物结构的gp120序列的检测
本发明还提供了一种确定来源于被治疗者的生物样品是否含有以稀有二硫化物结构为特征的gp120氨基酸序列的多肽和/或编码其的多聚核苷酸的诊断方法。稀有二硫化物结构可以代表与新近感染或在北美传播的一种主要的HIV-1新型变异的“传播表现型”。该方法包括分析样品含有的多肽,或编码gp120序列的多聚核苷酸,其为:(a)在一个或多个以下位点缺少一个或多个半胱氨酸残基:54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418和445;和/或(b)在除下列位点的位点包括一个或多个附加的半胱氨酸残基:24,29,34,54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418,445,493,495,499-501,503-508和510;计数是从HIV gp120的HXB-2株的gp120的N端的甲硫氨酸开始。在一个优选的实施方案中,gp120序列不是在V1结构域具有一个或多个附加的半胱氨酸的gp120序列的G亚型或在V4结构域具有一个或多个附加的半胱氨酸的gp120序列的E亚型。本发明的诊断方法可以使用任何能够检测多肽包括和/或编码具有稀有二硫化物结构的gp120氨基酸序列的多聚核苷酸的存在,和可选择的定量的分析方法。所使用的样品可以包括预期含有多肽包括和/或编码gp120氨基酸序列的多聚核苷酸的任何组织。血液或血液成分(如血清或血浆)可以方便地作为被分析的样品。
1.以gp120多肽为基础的分析
免疫分析通常可以很方便地被用于检测以稀有的二硫化物结构为特征的gp120多肽。使用免疫分析检测gp120多肽要考虑的,如,方式,标记系统等与在上述检测gp120抗体中的一样很重要。
优选的检测gp120多肽的免疫分析是竞争或非竞争的。在非竞争的免疫分析方法中,直接检测结合到特异抗体的gp120多肽的量。在竞争的分析方法中,样品中gp120多肽的量是通过间接测量附加的(外源的)取代(或竞争)特异的抗体的量而检测。
用于这些免疫分析中的抗体包括例如可通过上述方法产生的单克隆抗体和多克隆抗体。
2.以gp120多核苷酸为基础的分析
编码以稀有二硫化物结构为特征的gp120氨基酸序列的gp120多聚核苷酸通常使用将适合的核酸杂交到多聚核苷酸样品上来检测。核酸分子特异地杂交到存在于gp120多聚核苷酸中而不存在于样品中其他多聚核苷酸中的靶序列。在一个优选的实施方案中,核酸分子基本上与靶核苷酸互补。
可以根据本领所熟知的任何方法从样品中制备多聚核苷酸。通常的分离和纯化多聚核苷酸的方法在Tijssen ed.,(1993)Chapter 3 ofLaboratory Techniques in Biochemistry and Molecular Biology:Hybridization With Nucleic Acid Probes,Part L Theory and NucleicAcid Preparation,Elsevier,N.Y.and Tijssen ed中描述了。在一个优选的实施方案中,可以通过逆转录及随后的扩增从含有HIV-1病毒RNA样品中获得gp120多聚核苷酸。
i.以扩增为基础的分析
在一个实施方案中,以扩增为基础的分析可被用来检测,以及可选择的定量检测所感兴趣的gp120多肽。在这种以扩增为基础的分析中,样品中的gp120多聚核苷酸作为扩增反应的模板与含有可被检测的标记或标记系统成分的核酸引物反应。适合的扩增方法包括,但不局限于聚合酶链反应(PCR),逆转录PCR(RT-PCR),连接酶链反应(LCR)(见Wu and Wallace(1989)Genomics 4:560,Landegren et al.(1988)Science 241:1077和Barringer et al.(1990)Gene 89:117;transcription amplification(Kwoh et al.(1989)Proc.Natl.Acad.Sci.USA 86:1173),自身序列复制(Guatelli et al.(1990)Proc.Nat.Acad.Sci.USA 87:1874);点PCR和连接PCR等等。
如果需要测定gp120多聚核苷酸的含量,可以使用任何熟知的“定量”扩增方法。定量PCR通常包括使用相同的引物同时扩增已知量的对照序列。这提供了一个可以校准PCR反应的内部标准。定量PCR的详细细节在PCR Protocols,A Guide to Methods and Applications,Innis et al.,Academic Press,Inc.N.Y.,(1990)中描述。
ii.以扩增为基础的分析
核酸杂交仅仅包括在使探针与其互补的靶核酸序列通过互补碱基对能够形成杂交双链的条件下使核酸探针与样品中的多聚核苷酸接触。不能形成杂交双链的核酸被洗脱,仅留下杂交的核酸以便检测,典型地通过所附着的可检测的标记或标记系统成分检测。使用核酸杂交技术进行检测和/或定量的方法是本领域技术人员熟知的(见Sambrook et al.supra)。杂交技术通常在Hames and Higgins(1985)Nucleic Acid Hybridization,A Practical Approach,IRL Press;Gall and Pardue(1969)Proc.Natl.Acad.Sci.USA 63:378-383;和John et al.(1969)Nature 223:582-587中被描述。优化的杂交条件在Tijssen(1993)Laboratory Techniques in Biochemistry andMolecular Biology,Vol.24:Hybridization With Nucleic AcidProbes,Elsevier,N.Y.)中被描述。
在此使用的用于检测gp120多聚核苷酸的探针可以是这些多聚核苷酸的全长或短于全长。经验上短的探针被用于测试特异性。优选地,核酸探针在长度上至少大约15,更优选大约20个碱基或更长(见Sambrook et al.for methods of selecting nucleic acid probesequences for use in nucleic acid hybridization)。杂交探针的可视性允许定量去检测感兴趣的gp120多聚核苷酸的存在与否,且可以使用标准方法(如,用放射性探针标记核酸的密度计量学)定量gp120多聚核苷酸的水平。
许多其它的核酸杂交方法是本领域技术人员公知的。标准的方法包括三明治分析和竞争或取代分析。三明治分析是商用的检测或分离多聚核苷酸的杂交分析。此分析应用一个共价键地固定于固体支撑物上的“捕获”核酸和溶液中的标记的“信号”核酸。样品提供了靶多聚核苷酸。捕获核酸和信号核酸都杂交到靶多聚核苷酸上形成一个“三明治”杂交复合物。
在一个实施方案中,本发明的方法可被用于以阵列为基础的杂交方法。在此杂交方法中许多不同的杂交反应可以几乎“平行”进行。这提供了在一个实验中快速的、几乎同时的检测多个杂交。在以阵列为基础的方法中进行杂交反应的方法是本领域公知的(Pastinen(1997)Genome Res.7:606-614;Jackson(1996)Nature Biotechnology 14:1685;Chee(1995)Science 274:610;WO 96/17958,Pinkel et al.(1998)Nature Genetics 20:207-211)。
阵列,特别是核酸阵列可以根据本领域公知的方法进行。例如,在一个简单的实施方案中,“低密度”阵列可以通过在一个固体支持物(如,玻璃表面,膜等)上在不同的位置点种(如用手点种)不同的核苷酸而制备。该简单的点种方法可以自动地生成高密度的点种微阵列。例如美国专利5807522中描述的使用微毛细管轻击表面而在表面沉淀少量生物样品的自动系统。该方法可以重复产生高密度阵列。还可以通过寡核苷酸合成技术产生阵列。因此,如美国专利5143854和PCT专利公开号WO90/15070和92/10092中描述的使用高密度寡核苷酸微阵列的光指导的联合合成技术。高密度阵列的合成也在美国专利5744305;5800992和5445934中描述。
在一个优选的实施方案中,用于本发明的阵列包括“探针”核酸。然后这些探针可以与来自生物样品中的多聚核苷酸中的“靶”核苷酸序列杂交。作为选择,可以反过来,来自不同样品的多聚核苷酸被排列,然后可以被一个或两个不同标记的探针探测。
将核酸固定在各种固体表面的许多方法是本领域公知的。各种有机或无机聚合体以及其他天然的和合成的物质,可被用作固体表面的物质。例证性的固体表面包括,如,硝化纤维,尼龙,玻璃,石英,重氮化的膜(纸或尼龙),硅树脂,聚甲醛,纤维素和醋酸纤维素。另外,塑料如聚乙烯,聚丙烯,聚苯乙烯等也可被应用。其他可被应用的物质包括纸,陶瓷,金属,非金属,半导体物质等。另外,形成凝胶的物质也可以被应用。这些物质包括如,蛋白质(如,白明胶),脂多糖,硅酸盐,琼脂糖和聚丙烯酰胺。当固体表面有孔时,可依赖于系统的特性决定孔的尺寸。
在制备表面时,可使用多种不同的物质,特别如层状物,以获得不同的特性。例如,蛋白质(如,牛血清白蛋白)或大分子混合物(如,Denhardt’s溶液)可被应用以防止非特异结合,简单的共价连接,和/或增强的信号检测。如果化合物和表面之间需要共价键结合,表面通常被多功能或可以被多功能化。存在与表面且用于连接的官能团可以包括羧酸,乙醛,氨基基团,氰基基团,烯基团,羟基基团,含巯基团等。将各种化合物连接到各种表面的方法是熟知的,在文献中有大量描述。
阵列可以由各种尺寸的标靶成分组成,直径从大约1mm到大约1um。能够定量1cm2面积的荧光显像的相对简单的方法被描述了并在一个图象中可以获得大量的靶成分(见,Wittrup(1994)Cytometry 16:206-213,Pinkel et al.(1998)Nature Genetics 20:207-211)。
根据本发明的杂交分析可以应用微电机械系统实现,如Protiveris’多悬臂阵列。
iii.gp120多聚核苷酸的检测
通过可检测的标记检测上述以多聚核苷酸为基础的分析中的gp120多肽。在本发明的以多聚核苷酸为基础的分析中可以使用上述任何标记。标记可以在杂交或扩增之前或之后被加入到探针或引物或样品多聚核苷酸。被称为“直接标记”的是在进行分析之前直接附着或整合到被标记的多聚核苷酸的。相反地,被称为“间接标记”的是在杂交后被连接到杂交双链的。在间接标记中,杂交双链中的一个多聚核苷酸携带可与可检测标记结合的成分。因此,例如,探针或引物可以在杂交前被生物素连接。杂交后,抗生物素蛋白连接的荧光团可以连接到含有生物素的杂交双链,提供了一个很容易被检测的标记。对于多聚核苷酸的标记和检测方法的详细概述,参见LaboratoryTechniques in Biochemistry and Molecular Biology,Vol.24:Hybridization With Nucleic Acid Probes,P.Tijssen,ed.Elsevier,N.Y.,(1993))。
可以通过使用扩大被检测的靶多聚核苷酸的多聚核苷酸扩增系统增强杂交分析的敏感性。此系统的例子包括聚合酶链反应(PCR)系统和连接酶链反应(LCR)系统。最近在本领域被描述的其他方法是以核酸序列为基础的扩增(NASBAO,Cangene,Mississauga,Ontario)和Qbeta复制酶系统。
在一个优选的实施方案中,适于用在本发明的扩增为基础的分析中的一个引物包括两个荧光染料,一个“报告染料”,一个“淬灭染料。”当完整时,因为淬灭染料的作用,引物产生非常弱的荧光。当引物被切断或降解时(如通过聚合酶的外切酶活性,见下),报告染料发光且可被适当的检测系统检测。应用具有聚合酶和外切酶活性的(如TaqDNA聚合酶)的合适的DNA聚合酶进行多种技术的扩增(PCR,RT-PCR,RCA或其他扩增方法)。聚合酶合成新的DNA链,在此过程中,同时降解被标记的引物,从而导致荧光的增加。商售的此种荧光检测系统包括Applied Biosystems的ABI PrismSystems 7000,7300,7500,7700或7900(TaqMan)或Roche的LightCycler系统。
下面的实施例仅提供对本发明的方法的一种描述,但并不限制本发明。
实施例
实施例1
gp120多肽的表达
优选HIV-1gp120序列以含有异源信号序列和附加表位的融合蛋白形式表达。作为例子,优选的信号序列包括从单纯疱疹病毒(HSV1)gD糖蛋白和人组织血浆酶原激活剂(tPA)来源的那些序列。成熟HSV1 gD的前29个氨基酸作为附加表位发挥作用,其连接到HIV gp120的42位残基,计数从gp120的HXB2族的N端的甲硫氨酸开始(成熟gp120的12位残基)。
pCI.gD.gp120含有哺乳动物的转录单位和一个pUC载体骨架(pCI哺乳动物表达载体,其可从Madison WI的Promega公司购得)。转录单位含有巨细胞病毒(CMV)的快速早期启动子和人工的内含子,其后为信号序列编码区和在KpnI位点融合到HIV-1 gp120的42位残基的成熟HSV gD糖蛋白的前29个氨基酸。gp120序列以一个终止子结束并有一个如上所述的XhoI限制性内切酶位点。在载体中,其后是SV40poly-A序列和转录中止子。
pCI.tPA.gp120还含有哺乳动物转录单位和一个pUC载体骨架(pCI哺乳动物表达载体,其可从Madison WI的Promega公司购得)。转录单位含有CMV的快速早期启动子和人工的内含子,其后为编码tPApre-pro序列的前36个氨基酸的序列和在KpnI位点融合到HIV-1gp120的42位残基的成熟HSV1 gD糖蛋白的前29个氨基酸的编码区。Gp120序列以终止子结束并有一个XhoI限制性内切酶位点,其后是SV40 poly-A序列和转录终止子。
本发明的gp120多肽的编码序列可通过聚合酶链反应(PCR)扩增以产生从氨基酸残基42向氨基酸残基529(gp41的残基18)延伸的DNA片断。片段在5’端具有KpnI酶切点和一个终止子,随后是3’端的XhoI酶切点。这些酶切点有助于克隆到pCI.gD.gp120载体或pCI.tPA.gp120载体。
Gp120扩增产物被KpnI和XhoI限制性内切酶切断,应用商售的试剂盒分离1.5kb的gp120片段,如QIAquick PCR purification kit(Qiagen,Valencia,CA)。pCI.gD.gp120或pCI.tPA.gp120被KpnI和XhoI切断,应用商售的试剂盒分离4.3kb的载体片段,如QIAquickGel Extraction kit(Qiagen,Valencia,CA)。gp120片段被连接到两个载体上。将连接产物转化到Top 10大肠杆菌。制备DNA并用KpnI和XhoI消化,进行凝胶电泳仪确定转化物中含有所需构建。然后通过应用磷酸钙技术(Graham et al.,Virology 52:456-467(1973))瞬时转化到293T人胚胎肾细胞(Graham et al.,J.Gen.Virol.36:59-77(1977))以及随后应用多克隆兔抗gp120抗血清进行Westernblot分析条件培养基来检测基因的表达。
实施例2
病毒感染性和中和性分析
由于体外培养的HIV-1不可避免的具有选择的条件,因此HIV-1感染病人中病毒的传播准确的代表仅仅可以通过检测不需要中间的体外培养的分子克隆自来源于病人的物质(如血浆,白细胞,脑)的病毒序列而获得。所得到的来源于逆转录病毒RNA基因组的克隆的互补DNAs(cDNAs)而后可被插入稳定的以DNA为基础的表达系统而进一步分析。一个这样的表达系统是PhenoSenseTM HIV中性分析(在Richman,2003中详细描述)。简言之,分析产生表达克隆的HIV-1包膜蛋白的伪病毒,然后利用这些病毒进行病毒感染性分析。这些分析被用于确定在趋化因子受体使用(CXCR4或CCR5)及对可溶性CD4的敏感性方面的HIV包膜糖蛋白的表型和病毒中和抗体。表明这些分析与传统的病毒中和分析相关,该分析测量了抗体抑制激活的外周血单核细胞(PBMCs)的能力。
PhenoSenseTM分析比传统的方法有利,其在于其更快,更精确,且使用限定的病毒。这避免了在体外的病毒选择中引起的潜在的人为差错。PhenoSenseTM分析使用核酸扩增(RT-PCR)以从HIV阳性病人血浆中衍生HIV包膜序列(gp160)。应用常规的克隆方法将扩增的包膜序列整合到表达载体上(pCXAS)。表达载体可以从单个分离的分子克隆制备,或从在收集标本时可精确代表病人大量病毒拟种的大量序列库中制备。表达病人病毒包膜蛋白的重组HIV-1储存库(库或单个的gp160)通过将缺少HIV-1包膜蛋白的缺陷的HIV-1基因组病毒载体和含有感兴趣的HIV包膜蛋白的第二个表达载体共同转染到HEK293细胞来制备。HIV-1基因组载体是复制缺陷的,其在HIV包膜基因的删除区含有一个荧光素酶表达盒。具有病人病毒包膜蛋白的重组伪病毒和CXCR4和CCR5依赖控制病毒(NL4-3,JRCDSF)和双嗜性鼠类白血病病毒(A-MLV)的特异性对照,在转染48小时后收获,并在具有4倍稀释的单克隆抗体和/或血浆对照下在37℃孵育1小时。表达CD4/CCR5的U87细胞和表达CD4/CXCR4的细胞被病毒抗体稀释液接种。接种72小时后通过测量感染病毒中荧光素酶活性确定病毒的感染效率,并用平衡的相对的光单位(RLUs)记录。通过对比在每种抗体浓度与抗体阴性对照中的病毒复制的抑制百分比(荧光素酶活性)表示中和活性。用抑制病毒感染活性50%时所需的单克隆抗体的浓度定义IC50。如果IC50是使用相同试剂的特异性对照病毒,A-MLV的IC50的至少3倍时,病毒被划分为中和性敏感类。
实验结果
三种半胱氨酸突变,U-099(具有19个半胱氨酸残基),U-209具有19个半胱氨酸残基)和U-210(具有20个半胱氨酸残基)被加到PhenoSenseTM感染性和中和性分析中,结果在表2中表示。每种被结合的病毒感染表达CD4和CCR5趋化因子受体的U87细胞,而不是表达CD4和CXCR4共同受体的U87细胞,这表明这些突变的病毒专有地是R5表型。使用特异于gp41(4E10和2F5)和gp120(2G12)的单克隆抗体(MAbs)分别将病毒中和。19-半胱氨酸突变的U-099对gp41MAbs的抗性是使用其它突变的2-8倍,但中和性相同与gp120 MAb 2G12的其他突变株。有趣的是,U-210并不能被认为可以广泛中和初始HIV分离物的MAb,2G12中和(见Trkola等,1996)。然而,因为2G12结合是V4区突变敏感的,且U-210在此区具有2个额外的半胱氨酸残基,不能中和可能是由这些半胱氨酸突变介导的。研究结果表明拥有19和20个半胱氨酸残基而不是典型的拥有18个半胱氨酸残基的HIV分离物,是有功能的并可以调节含有CD4和CCR5趋化因子受体的细胞感染。
表2
应用抑制病毒感染性50%所需的单克隆抗体(MAb)的浓度定义IC50的值。MAbs 4E10和2F5的靶区位于gp41,而MAb 2G12识别gp120的抗原决定簇。92HT594是双极病毒对照。JRSCF和NL43分别是R5和X4定向的对照。A-MLV是可感染两种细胞(R5或X4)但不被HIV MAbs抑制的非HIV对照。NA;不可应用。
在U87 CD4/CCR5细胞中的检测 | IC50 | ||||
病毒 | 在R5细胞中生长? | 病毒的定向 | 4E10(ug/ml) | 2F5(ug/ml) | 2G12(ug/ml) |
92HT594 | 生长 | 双向 | 2.941 | 0.857 | 1.940 |
U-210 | 生长 | R5 | 0.915 | 0.438 | >50.0000 |
U-209 | 生长 | R5 | 0.686 | 1.022 | 2.643 |
U-099 | 生长 | R5 | 5.494 | 2.295 | 1.298 |
JRCSF | 生长 | R5 | 7.911 | 2.104 | 0.764 |
NL43 | 不生长 | X4 | NA | NA | NA |
A-MLV | 生长 | 非-HIV | >50 | >50 | >50 |
在U87 CD4/CXCR4细胞上检测 | IC50 |
病毒和对照的定向 | 在X4细胞上生长? | 病毒的定向 | 4E10(ug/ml) | 2F5(ug/ml) | 2G12(ug/ml) |
92HT594 | 生长 | 双向 | 2.667 | 0.748 | 2.392 |
U-210 | 不生长 | R5 | NA | NA | NA |
U-209 | 不生长 | R5 | NA | NA | NA |
U-099 | 不生长 | R5 | NA | NA | NA |
JRCSF | 不生长 | R5 | NA | NA | NA |
NL43 | 生长 | X4 | 1.415 | 0.477 | 0.473 |
A-MLV | 生长 | 非-HIV | >0 | >50 | >50 |
参考文献
1.Riehman DD,Wrin T,Little SJ,Petropoulos CJ.(2003).Rapidevolution of the neutralizing antibody response to HIV type 1infection.Proceedings of the National Academy of Sciences U SA.100(7):4144-4149.
2.Trkola A,Purtscher M,Muster T,Ballaun C,Buchacher A,Sullivan N,Srinivasan K,Sodroski J,Moore JP,and Katinger H.(1996).Human monoclonal antibody 2G12 defines a distinctiveneutralization epitope on the gp120 glycoprotein of HumanImmunodeficiency Virus Type 1.Journal of Virology 70(2):1100-1108。
在说明书中提到的所有的文献和专利在此被同等地引作参考,即使某些文献或专利被特别提到和特别指出在此处引作参考。
<U-101c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGGATCAGGAGGAATTGTCAGCGCTGGTGGAGATG
GGGCATCATGCTCCTTGGAATGTTGATGATCTGTAATGCTGTAGGACAATTGTGGGTTACGGTCTATTAT
GGGGTACCTGTGTTGGAAAGAAGCCACCACCACTCTATTCCGTGCATCAGATGCTAAGCATATGATACAG
AGGTACATAATGTCTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAATAGAATTGGA
AAATGTGACAGAAACTTTTAACATGTGGAAAAATAACATGGTAGAACAAATGCATGAGGATATAATCAGT
TTATGGGATCAAGGCCTAAAACCATGTGTAAAATTAACCCCACTCCGTGTTACTTTAAATTGCACTGACT
ACAAGAATGCTAATAGTACCAATAATAATAGTACCAGTGATAGTAGCAATCTAGAAGAGGAGGAAAGGAA
AATAAAAAACTGCTCTTTCAATATCACTACAAGCATAAAAGATAGGATGCAGAAAGAATATGCACTTTTT
TATAAACTTGATATAGTACCAATAGATAATAATAATACTAGATATAGGATGATAAGTTGTAACACCTCAG
TCATTACACAGGCCTGTCCAAAGGTATCTTTTGAGCCAATTCCCATACATTATTGTGCCCCGGCTGGTTT
TGCGATTCTAAAATGTAAGGATAAGAAGTTCAATGGAACAGGACCATGTAGAAATGTCAGCACAGTACAA
TGTACACATGGAATTAGGCCAGTAGTATCAACTCAATTGCTGTTAAATGGCAGTCTAGCAGAAGAAGAGG
TAGTACTTAGATCTGAAAATTTCACGAACAATGCTAAAACCATAATAGTACAGCTAAAAGAACCTATAAA
AATCAATTGTACAAGACCCAACAACATACAAGAAAAGTATACATATATAGGACCAGGGAGAGCATTTTAT
ACAACAGGGGAGATAATAGGAGACATAAGACAAGCACATTGTAGCATTAGTAAGGTAGAATGGAACAACA
CTTTGATACAAATAGTTGAAAAATTAAGAGAACAATTTGGGACTAAAACAATAAATTTTACTAAACCCTC
AGGAGGGGACCTAGAAATTGTAACGCACAGCTTTAATTGTAGAGGGGAATTTTTCTACTGTAATACCACA
AAACTGTTTAATAGTACTTGGCCTGGGAATATTACTTGGACTCGGAATAATAATGTTACTACAGAAAATA
TCACACTCCCATGCAGAATAAAACAAATTGTGAACAGATGGCAGGAAGTAGGAAAAGCAATGTATGCCCC
TCCCATCCAAGGACAAATTAGATGTTCATCAAATATTACAGGGCTGCTATTAACAAGAGATGGTGGTGGG
GACCAGAATAGCACAGGGGAGATCTTCAGACCTGGAGGAGGAGATATGAGGGACAATTGGAGAAGTGAAC
TATACAAATATAAAGTAGTACAAATTGAACCATTAGGAATAGCACCCACCAAGGCAAGGAGAAGAGTGGT
GCAGAGAGAAAAAAGAGCAGTGGGAACATTAGGAGCTATGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGC
ACT
<U-101c1;PRT/1;HIV-1>
NAVGQLWVTVYYGVPVWKEATTTLFRASDAKAYDTEVHNVWATHACVPIDPNPQEIELENVTETFNMWKN
NMVEQMHEDIISLWDQGLKPCVKLTPLRVTLNCTDYKNANSTNNSTSDSSNLEEEKGEIKNNCSFNITTS
IKDRMQKEYALFYKLDIVPIDNNNTRYRMISCNTSVITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFN
GTGPCRNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVLRSENFINNAKTIIVQLKEPIKINCTRPNNNTR
KSIHIGPGRAFYTTGEIIGDIRQAHCSISKVEWNNTLIQIVEKLREQFGTKTINFTKPSGGDLEIVTHSF
NCRGEEFYCNTTKLFNSTWPGNITWTRNNNVTTENITLPCRIKQIVNRWQEVGKAMYAPPIQGQIRCSSN
ITGLLLTRDGGGDQNSTGEIFRPGGGDMRDNWRSELYKYKVVQIEPLGIAPTKARRRVVQREKR
<U-178c13;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAAAGTGACGGGGATCAGGAAGAATTGTCAGCGCTTGTGGAGATG
GGGCATGATGCTCCTGGGGATGTTAATGATCTGTAGTGCTGCAGAACAATTGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATCAGATGCTAAAGCATATGACGCAG
AGAAACATAATGTTTGGGCCACACATGCCTGCGTACCCACAGACCCCAACCCACAAGAAATAGTATTGGA
AAATGTGACAGAATATTTTAATGCTTGGAAAAATAACATGGTAGAACAGATGCATGAGGATATAATCAGT
TTATGGGATCAAAGCCTAAAACCATGTGTAAAATTAACCCCACTCTGTGTTACTTTAAATCGCACTGATT
TGAATAATAGTACTAACACCACTAATAGTAATAGCAGCGGGGGGATGATGAGAGAAGAAATGAAAAACTG
CTCTTTCAATATCACCACAATAATAGGAGATAGGAGGCAAAAAGAATATGCACTTTTTTATAAACTTGAT
ATAGCATCAATAAAGGATGATGCTAATAATTTCACATATAGGTTGATAAGTTGTAACACCTCAGTCATTA
CACAAGCCTGTCCAAAGATATCCTTTGAGCCAATTCCCATACATTATTGTGCCCCGGCTGGTTTTGCAAT
TCTAAAGTATAACGATAAGAAGTTCAATGGAGAAGAGCAATGTAAAAATGTCAGCACAGTACAATGTACA
CATGGAATTAAGCCAGTAGTATCAACTCAGCTGCTGTTAAATGGTAGTCTAGCAGAAGAAGAGATAGTAA
TTAGATCTGACAATTTCACAGACAATGCTAAAACCATAACAGTACAGCTGAATGAATCTGTAGTAATTAA
TTGTACAAGACCCCACAACAATACAAGAAAAAGTATAAATATAGGACCAGGGAGAGCATGGTATACAACA
TAAAGATAGTTAAAAAATTAAGAGAACAATTTAATACAAACACCATAATCTTTAATCAATCCACAGGAGG
GGACCTAGAAATTGTAATGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGTGATACAACACAACTG
TTTAATAGTACTTGGAATATTACTGGAGAAAGTACTTGGAATAGTACTGGAAAGGCAAATGAAACTATCA
CACTCCCATGTAGAATAAAACAAGTTATAAACATGTGGCAGCAACTAGGGAAAGCAATGTATGCCCCTCC
CATCAAAGGGCAAATTAGATCTTCATCAAATATTACAGGGCTGCTATTAACAAGAGATGGTGGTAAGAAC
AGCAGTAAGGGGACTGAGACCTTTAGACCTGGAGGAGGAGATATGAGGGACAATTGGAGAAGTGAATTAT
ATAAATATAAAGTAGTAGAAATTGAACCATTAGGAATAGCACCCACTAAGGCAAAGAGAAGAGTGGTGCA
GAGAGAAAGAAGAGCAGTAATAGGAGCTATGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-178c13;PRT/1;HIV-1>
SAAEQLWVTVYYGVPVWKEATTTLFCASDAKAYDAEKHNVWATHACVPTDPNPQEIVLENVTEYFNAWKN
NMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNRTDLNNSTNTTTNSNSSGGMMREEMKNCSFNTTTIGDR
RQKEYALFYKLDIASIKDDANNFTYRLISCNTSVITQACPKISFEPIPIHYCAPAGFAILKYNDKKFNGE
EQCKNVSTVQCTHGIKPVVSTQLLLNGSLAEEEIVIRSDNFTDNAKTITVQLNESVVINCTRPHNNTRKS
INIGPGRAWYTTGEIIGDIRQAHCNISKTQWNNTLIKIVKKLREQFNTNTIIFNQSTGGDLEIVMHSFNC
GGEFFYCDTTQLFNSTWNITGESTWNSTGKTNETITLPCRIKQVINMWQQVGKAMYAPPIKGQIRCSSNI
TGLLLTRDGGKNSSNGTETFRPGGGDMRDNWRSELYKYKVVEIEPLGIAPTKAKRRVVQRERR
<U-013c6;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGATGGGGATGAGGAAGAATTATCAGCACTGGTGGAGAGG
GGGCATCTTGCTCCTTGGGATGTTAATGATCAGTAGTGCTATAGAAAATTCGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGTGAAAGAAGCTACCACCACTTTATTTGTGCATCAGATGCTAAAGCTTATGAAACAG
AGGCACATAATGTTTGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAATAAAATTGGGA
AAATGTGTCAGAAATTTTAACATGTGGAAAAAATAACATGGTAGACCAAATGCATGAGGATATAATCAGT
TTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCACTCTGTGTTACTTTAAATTGCACTGATT
ATTTTGGGAATACTACTAATACCAATACTAATACCACCAGTAGTCCCAGCACCAACAGTAGTAATGAAGG
AGAAGTGAAAAAATGCTCTTTCAATATCACCACAGAAGTAAGGGACAAGGTGCGAAAAGAATTTGCACTT
TTTTATAAACTTGATATAGTACGAACAGGTCATGATAATACTAGCTATAGGTTGATAAGTTGTAACACCT
CAGTCATTACACAGGCCTGCCCAAAGATATCCTTTGATCCAATTCCCATACATTATTGTGCCCCGGCTGG
TTTTGCGATTCTCAAGTGTAGAGATAATAAATTTAATGGAACAGGACCATGTAAAAATGTCAGCACAGTA
CAATGTACTGATGGAATTAGGCCAGTAATATCAACTCAACTACTGTTAAATGGCAGTCTAGCAGAAGAAG
AGGTAGTAGTTAGTCTAAAAAATTTCACAAACAATGCTGAAGTCATAATAGTGCAGCTGAAAGAATCTGT
ACAAATAAATCGTACAAGACCCAACAACAATACAAGGAAAAGTATACCTATGGGTCCAGGGAGAGCATGG
TATGCAGAAGAAGATATCATAGGAAATATAAGACAGGCACATTGTAACATTAGTGGAGTAAAATGGAATT
ACACTTTACAGCAAATAGTTAAAAAATTAAGAGAGCAATTTAAAAATAAAACAATAAAGTTTCAGCCATC
CTCAGGAGGGGACCCAGAAATTGTAAGGCACAGTTTTAATTGTAGAGGGGAGTTTTTCTACTGTGATACA
ACACTACTGTTTAATAGTACTTGGAATAGTAATGATACTTGGAATAGTACTGAAGGGTCAAATGACACTA
TTACACTCCCGTGTAGAATAAAACAAATTGTAAACATGTGGCAAGAAGTAGGAAAAGCAATGTATGCTCC
TCCCATCAAAGGACAACTTAACTGTTCATCAAATATTACAGGGCCGATATTAACAAGAGATGGTGGTAAG
GGTGAGAACTCGACCGAGAACAATACTGAGATATTCAGACCTGGAGGAGGAGATATGAGGGACAATTGGC
GAAGTGAATTATATAAATATAAAGTAGTACAAATTGAACCATTAGGAATAGCACCCACTAAGGCAAAGAG
AAGAGTGGTGCAGAGAGAAAAAAGGAGCGGGACTGTTTTTTTCCTGGGGTTCTTGGGAACAGCAGGAAGC
ACT
<U-013c6;PRT/1;HIV-1>
SAIENSWVTVYYGVPVWKEATTLFCASDAKAYETEAHNVWATHACVPIDPNPPQEIKLENVSENFNMWKN
NMVDQMHEDIISLWDQSLKPCVKLPLCVTLNCTDYFGNTTNTNTNNITTSSPSTNSSNEGEVKKCSFITT
EVRDKVRKEFALFYKLDIVRTGHDTSYRLISCNTSVITQACPKIDSFDPIPIHYCAPAGFAILKCRDNKF
NGTGPCKNVSTVQCTHGIRPVISTQLLLNGSLAEEEVVVRSKNFTNNAEVIIVQLKESVQINRTRPNNNT
RKSIPMGPGRAWYATEDIIGNIRAQAHCNISGVKWNNTLQIVKKLREQFKNKTIKFQPSSGGDPEIVRHS
FNCRGEFFYCDTTLLFNSTWNSNDTWNSTEGSNDTITLPCRIKQIVNMWQEVGKAMYAPPIKGQLNCSSN
ITGPILTRDGGKGENSTENNTEIFRPGGGDMRDMRDNWRSELYKYKVVQIEPLGIAPTKAKRRVVQREKR
<U-016c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCCAATGAGAGTGAAGGGATCAGGAAGAATTATCAGCACTTGTGGAGATG
GGGCATCATGCTCCTTGGGATGTTGATGATCTGTAATGCTGCAGAACAGTTGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGGAGGGATGCAAATACCACTCTATTTTGTGCATCCGATGCTAAACCATATGATACAG
AGGTACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTAGTATTGGA
AAATGTGACAGAAAGCTTTAACATATGGAAAAATAACATGGTAGAACAAATGCATGAGGATATAATCAGT
TTGTGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCACTCTGCGTTACTTTAAATTGCAGTAATT
TAAGTACCACTAATAATAATACCATTAGTGGTAATGAGACAGCAGTAAATAAAGGAGAAATAAAAAAACG
CTCTTTCAATGTCACCACAAACATAAGAGATAGGGTAAAGAAGAATATGCGCTTTTTTTATAATCTTGAT
TTAGTACAAATAGGTGATTCTAATACTAGCTATACAATGGTAAAGTGTAACACCTCAGTCATTACACAGG
CCTGTCCAAAGGTACCCTTTGAGCCAATTCCCATACATTTTTGTGCCCCAGCTGGTTTTGCGATTCTAAA
GTGTAATAATAACACGTTCAGTGGAAAAGGAGAATGTACAAATGTCAGCACAGTACAATGTACGCATGGA
ATTAGACCAGTAGTATCAACTCATCTGCTGTTAAATGGCAGCTTAGCAGAAGAAGACATAGTAATTAGAT
CTGACAATTTCACGGACAATACTAAAACCATAATAGTACAGCTAGACAATACTATAAACATTACTTGTAC
CAGACCCAACAATAATACAAGGAAAGGTATACATATAGGACCAGGGAGAGCATTTTATGCAACAGGGGAT
ATAATAGGAAATATAGACAAGCACATTGTAACCTTAGTAAAACACATTGGAATAACACTTTAAAAACAGA
TAGTTAAAAAATTAAGAGAACAATTTAAAAATAAAACAATAGTCTTTAATCAATCTACAGGAGGGGACCC
AGAAATTGTACAGCACACTTTTAATTGTAGAGGGGAATTTTTCTATTGTAACTCAACACCACTGTTTAAT
AGTACTTGGTATCCTAATAGTACATTGGATGAAACAAACAGCACAGACAACAATGAAACTATCACACTCC
AATGCAGAATAAGACACAAATTATAAACATGTGGCAAGTAGGGAAAAGAATGTATGCCCCTCCTATCCAG
AGGACAAATTACATGCATCAAATATTACAGGGCTGTGATATTAACAAGAGATGGTGGAGATAACAATGAA
ACTGAGATCTTCAGGCCTGGAGGAGGCAATATGAAGGATAATTGGAGAAGTGAATTATATAAATATAAAG
TAGTAAAAATTGAGCCATTAGGAATAGCACCACTAAGGCAAAGAGAAGAGCGGTGCAGAGAGAAAAAAAG
AGCAGCGGGAATAGGAGCTGTGTTCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-016c1;PRT/1;HIV-1>
NAAEQLWVTVYYGVPVWRDANTTLFCASDAKAYDTEVHNVWATHACVPTDPNPQEVVLENVTESFNIWKN
NMVEQMHEDIISLWDQSLKPCVKLTPTLCVTLNCSNLSTTNNTISGNETAVNKGEIKNRSFNVTTNIRDR
VKKEYALFYNLDLVQIGDSNTSYTMVKCNTSVITQACPKVPFEPIPIHFCAPAGFAILKCNNKTFSGKGE
CTNVSTVQCTHGIRPVVSTHLLLNGSLAEEDIVIRSDNFTDNTKTIIVQLDNTINITCTRPNNNTRKGIH
IGPGRAFYATGDIIGNIRQAHCNLSKHWNNTLKQIVKKLREQFKNKTIVFNQSTGGDPEIVQHTFNCRG
EFFYCNSTPLFNSTWYPNSTLDETNSTDNNETITLQCRIRQIINMWQEVGKAMYAPPIRGQITCTSNITG
LILTRDGGDNNETEIFRPGGGNMKDNWRSELYKYKVVKIEPLGIAPTKAKRRAVQREKR
<U-032_3c4;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAAAGTGAAGGAGACCAGGAAGAATTATCAAAGCTTGTGGAGAGG
GGGCACCTTGTTCCTTGGAATGTTGATGATCTGTAGTGTTACAGGACAATTGTGGGTTACAGTCTATTAT
GGGGTACCTGTGTGGAAAGAGGCAACCACCACTCTATTTTGTGCATCAAATGCTAAAGCATATGATACAG
AGGTACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACGCACAAGAAGTAGTATTAGA
AAATGTGACAGAATATTTTGACATGTGGAAAAATGACATGGTAGAACAAATGCATGAGGATGTAATCAGT
TTATGGGATCAAAGCCTAAAGCCATGTIAGAATTAACCCCCACTCTGTGTTACTTTAAATTGCACTGATG
TGAATATTACTAATACCAATAATAGTACCATTAACAATAGTAGTAATAATACCAATAGTAGTGATTGGGA
ACGGATGGAGCCAGGAGAAATAAAAAACTGCTCTTTCAATAGCACCACAAACATGAGAGATAGGACGCAG
AGAGAATACGCACTTTTTATAAACTTGATATAGAACCAGTAGATAATAAAAGTAATAATAAAAAGTCTTA
ATGAAAGTATTAGTAAAAGTATTACTTATAGGTTAATAAGTTATAACACCTCAGTCATTAAACAGGCCTG
TCCAAAAGTCATCTTTTGAGCCAATTCCCATACATTATTGTGCCCAGCTGGTTTTGCAATTCTAAAGTGT
AATAATGAGACATTCGATGGAAAAGGAGAATGTAGAAATGTCAGCACAGTACAATGTACACATGGAATTA
GGCCAATAGTGTCAACTCTGCTGCTGTTAAATGGCAGTCTAGCAGAAAAAGGACTAGTAATTAGATCAAA
CAATTTCTCGGACAATGCTAAAACCATAATAAGTACATCTGAATTGAATCTATAACAATTAAGTATAAGA
CCCAACAATAATACAAGAAAAAGTATACATATAGCACCAGGAGCGCATTTTTATGCAACAGGAGACATAA
TAGGAGATATAAGGCAAGCACATTGTAACATTAGTGCAAAAAATTGGATTAACACTTTAAAACAGATAGT
TATAAAACTAAAAGGAAAATATAATACTAGTACAAAAATAGACTTTAAGCCATCCTCAGGAGGGGACCCA
GAAATTGTAATGCACAGCTTTAATTGTGGAGGGGAGTTTTTCTACTGTAATACATCAAAACTGTTTAATA
ATACTTGGAAGGAGAATAATACTTTAGAGTCAAATGATACTATGGAGATCATTAACGAAACTATTATACT
CCCATGTAGAATAAAACAGTTTATAAACATGTGGCAGAAAGTGGGAAAAGCAATGTATGGCCCTCCCATC
AGAGGACAAATTAAATGTGAATCAAATATTACAGGGCTGCTATTAACAAGAGATGGTGGTAATACAAATA
GCACGAACGGGACCGAGACCTTCAGACCTGGAGGAGGAAATATGAAAGACAATTGGAGAAGTGAATTGTA
CAAATATAAAGTAGTAAAAATTGAACCAATAGGAATAGCACCCACCAGGGCAAAAAGAAGAGTGGTGCAG
AGAGAAAAAAGAGCAGTGGGAATAGGAGCTGTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-032_3c4;PRT/1;HIV-1>
SVTGQLWVTVYYGVPVWKEATTTLFCASNAKAYDTEVHNVWATHACVPTDPNAQEVVLENVTEYFDMWKN
DMVEQMHENVISLWDQSLKPCVELTPLCVTLNCTDVNCTDVNINNSSNNSSNTNSSDWERMEPGEIKNCS
FNSTTNMRDRTQREYALFYKLDIEPVDNKSNNKSLNESISKSIYTRLISYNTSVIKQACPKVSFEPIPIH
YCAPAGFAILKCNNETFDGKGECRNVSTVQCTHGIRPIVSTQLLLNGSLAEKDIVIRSNNFSDNAKTIIV
HLNESITIKCIRPNNNTRKSIHIAPGSAFYATGDIIGDIRQAHCNISAKNWINTLKQIVIKIKGKYNTST
KIDFKPSSGGDPEIVMHSFNCGGEFFYCNTSKLFNNTWKENNTLESNDTMEIINETIILPCRIKQFINMW
QKVGKAMYAPPIRGQIKCESNITGLLLTRDGGNTNSTNGTETFRPGGGNMKDNWRSELYKYKVVKIEPIG
IAPTRAKRRVVQREKR
<U-051c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGGATCAGGAAGAGTTGCTTGTGGAAATGGGGCAC
CTTGTTCCTTGGAATGTTGATGATCTGTAGTGCTGTAGAACAATTGTGGGTCACAGTTTATTATGGAGTA
CCTGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATCAGATCTACAGGCATATATTCCAGAGGTAC
ATAATGTATGGGCCACACATGCCTGTGTACCCACAGATCCCAACCCACAAGAAGTAGAATTGAAAAATGT
GACAGAGGATTTTTAATGTGGAAGAATAACATGGTAGAACAAAATGCATGAAGATGTAATCAGTTTATGG
GATCAAAGCCTAAAGCCATATGTGGAATTAACCCCACTCTGTGTTACGTTAAATTGCACTGATTATTGGG
GGGATACTACTCGTGCCGGAAATACTACTGCTAGTGTCACTAGTACTGCTAATGTCACTAGTAGTAAAGA
GGTACAAATGAAAAACTGCTCTTTCTATGTCTCCACAAACATGATGGATAAGAAACAGAAAGAATACGCA
CTTTTTTATAAACTTGATGTAGTGCCAATAGGTAATGAGACTAATGGTAAGGAGACAATATATAGCTATA
GGTTAATAAGTTGTAACACCTCAGTAGTTACCCAAGCCTGTCCAAAGGTAACCTTTGAGCCAATTCCCAT
ACATTATTGCCCCGGCTGGTTTTGTTGATTCTAAAGATGCAAGGATAAGAGGTTCAATGGAACAGGACCA
TGTACAAATGTCAGCACAGTACAATGTACACATGGAATTAGGCCAGTAGTATCAACTCAACTACTGTTAA
ATGGCAGCTTAGCAGAAGAAGATATAGTACTTAATCTGAAAATTTCTCGAAACAATGCTAAAAACATAAT
AGTACAGCTGAATGAATCTGAGTAATTATTGTACAAGCCTCAACAACAATACAACAAGAAAAGCATACAT
ATGGGGCCAGGGAAAGCATTTTATGCAACAGGAGACACCATAGGAGATATAAGACAAGCACATTGTAACA
TTAGTGAAGAGGCCTGGAATAAAACTCTAAGACGAATAGCTATAAAATTAAAAGAACAATTTAATATAAC
AGACAAAGTAATCTTTAAACCCTCCTCAGGAGGGACATAGAATTCCAATGGCACCAGTGTTAATTGTGGA
GGGGAATTTTTCTATTGTAATACAACACAGCTGTTTAATAGTACTTGGAATGAAACACAGCTGAATAGTA
GTACTGTGAATAAATATTACAAGGTCAGACAACAACATCACACTCCCATGCAAATAAAGCAAATTGTAAA
CATGTGGCAGAAAATAGGAAAAGCAATGTATGCCCCTCCATCAGTGGACTATTAGATGTGTAAATCAAAT
ATTACAGGGATAATATTAGCAAGAGATGGTGGTAATAATGGCACAAATGATACGAGGACCTTCAGACCTG
TAGGAGGAAATATGAAGGACAATTGGAGAAGTGAATTATATAAATATAAAGTAGTAAGAATTGAACCATT
AGGAGTAGCACCCACCAAGGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCAGTGGGACTAGGAGCT
ATGTTCCTTGGGTTCTGGGGAGCAGCAGGAAGCACT
<U-051c1;PRT/1;HIV-1>
SAVEQLWVTVYYGVPVWKEATTTLFCASDAKAYIPEVHNVWATHACVPTDPNPQEVELKNVTEDFNMWKN
NMVEQMHEDVISLWDQSLKPYVELTPLCVTLNCTDYWGDTTRAGNTTASVTSTANVTSSKEVQMKNCSFY
VSTNMMDKKQKEYALFYKLDVVPIGNETNGKETNNSYRLISCNTSVVTQACPKVTFEPIPIHYCAPAGFV
ILKCKKKRFNGTGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEEDIVVLSENFSNNAKNIIVQLNESVVI
NCTRLNNNTRKSIHMGPGKAFYATGDTIGDIRQAHCNISEAWNKTLRRIAIKLKEDQFNITDKVIFKPSS
GGDIEIAMHSVNCGGEFFYCNTTQLFNSTWNETQLNSSTVNNITRSDNNITLPCKIKQIVNMWQKIGKAM
YAPPISGLIRCKSNITGIILARDGGNNGTNDTRTFRPVGGNMKDNWRSELYKYKVVRIEPLGVAPTKAKR
RVVQREKR
<U-052c1;DNA;HIV-1>
AGAAAGAGCAGAACAGTGGCAATGAGAGTGGAAGGGGGATCGGAAGAATTGTCAGCCGCTTGTGGAAATG
GGGCACCATGCTCCTTGGGATGTTAATGATCTGTAGGGCTGCAGAGCAATTGTGGGTCACAGTCTATTAT
GGAGTACCTGTGTGGAGAGAAGCAAACACCACTCTATTTTGTGCATCAGATGCTAAAGCATATGATACAG
AGGTACATAATGTTTGGCCACACATCCTGTGTACCCACAGACCCTAACCCACAAGAATGTAGTATTGGGA
AAATGTGACAGAAAATTTTAATGTGTGGAAAAATAACATGGTAGAACAGATGATGAGGATATTAATCAGT
CTATGGGATCAAAGCCTAAAACCATGTGTAAAATTAACCCCAACCTGTGTTACTTTAAATTGTAATACCA
TTAATGCCACTAAAGATATGATAGGAGAATTAAAAAACTACTGCTCTTTCAACACCACAAGCATAAGAGA
TAAGTGGGCAAAAAGAATATGCACTTTTTTATAAACTTGATGTAGTGCCAATAGATGATATGGTAATGAT
ACTGGTAATGGTACGCTATAGGCTAATAAGTTGTAATAACCTCAGTCATTACACAGGCCTGCAAAGACAT
CCTTTGAGCCAAATTCCCATACATTATTGTGCCCCGGCTGGTTTTGCGATTCTAAAGTTAACAATAAAAA
GTTCAATGGAACAGGACCACGTAAAAATGTCAGCACACGTAACAATGTACATGGAATTAGGCCAGTAGTA
TCTACTCAACTGTTGTTAAATGGCAGTCTAGCAGAAGCCAAGAGATAGTACTTAGATCTGAATTTCTCAA
ACAATGCTAAAACCATAATAGTACAATTGAATGAATCTATAGTAATTAATTGTACAAGACCCAACAACAA
TACGAGAAAAAGTATACATATAGGACCAGGGAGAGCATTTTATGCAGCAGGAGAAATAATAGGAGATATA
AGAACAGCACATTGTAACATTAGTGGAACAAAATGGAATAACACTTTTAAAACAGATAGTTGTAAAATAA
GAGAACAATTTGGAAATAAAACAATGGTCTTTAGTCACTCCTCAGGAGGGGACCCGGAAATTGTAAGGCA
CAGTTTTAATTGTGGAGGGGAATTTTTCCATTGCAATACAACACAACTGTTTAATAGTAGTTGGCCTTGG
AATGGTACTGAAGGGTCAAATAACACTGAAGGAAATGACACAATCACCCTCCCATGCAGAATAAAACAAA
TTATAAACATGTGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATCAGAGGGGTAATTAAATGTTC
ATCAAATATTACAGGGCTATTATTAACAAGAGATGGGGGTACTAACAGGACCGACAATGGGAGCGAGGTC
TTCAGACCTGGGGGAGGAGATATGGGACAACGAATTGGAGTAGTGAATTATAAAAAATAAGTAGTAAGAA
TTGAACCATTAGGAGTAGCACCCACCAAGGCAAAGAGAAGAGTGGTGCAGAGAAAAAAAAAAGCAGTGGG
ACTAGGAGCTATGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-052c1;PRT/1;HIV-1>
RAAEQLWVTVYYGVPVWREANTTLFCASDAKAYDTEVHNVWATHACVPTDPNPQEVVLENVTENFNMWKN
NMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCNTINATKDMIGELKNCDSNITTSIRDKWQKEYALFYK
LDVVPIDDNGNDTGNGSYRLISCNTSVITQACPKTSFEPIPIHYCAPAGFAILKCNNKKFNGTGPRKNVS
TVQCTHGIRPVVSTQLLLNGSLAEEEIVLRSENFSNNAKTIIVQLESIVINCTRRPNNNTRKSIHIGPGR
AFYAAGEIIGDIRTAHCNISGTKWNNTLKQIVVKLREQFGNKTMVFSHSSGGDPEIVRHSFNCGGEFFHC
NTTQLFNSSWPWNGTEGSNNTEGNDTITLPCRIKQIINMWQEVGKAMYAPPIRGVIKCSSNITGLLLTRD
GGTNRTDNGSEVFRPGGGDMRDNWSSELYKNKVVRIEPLGVAPTKAKRRVVQREKR
<U-065_3c1;DNA;HIV-1>
AGAAAGAGCGAAGACAGTGGCAATGAGAGTGAGGGGGATCATGAGGAATTATCAGTACTTATGGAAATGG
GGCACCATGCTCCTGGGGATATTGATGATCTGTAATGCTAGTGAAAAATTGTGGGTCACAGTCTATTATG
GGGTACCTGTGTGGAAAGAGGCAAACACCACTCTATTTTGTGCATCAGATGCCAAAGCTTATGATACAGA
AGTACATATGTTTGGCCACACATGCCTGTGTACCCACAGACCCCCCGCCCCTCAAGAAGTACTATTGGGA
AATGTGACAGAAAATTTTAACATGTGAAAAATAACATGGTAGAACAAATGCATGAGGATATAATCCAGTT
TATGGGATCAAAGCCTAAGCCATGTGTAAAATTAACCCCACTCTGTGTTACTTTAAAATTGCACTAACTT
GAATGATACTAATATCAGTAGTAGTAATGTTAGTACCCATAATAGTAGTGGCATAGGAGAAATGAAAAAT
TGCTCTTTCAATGTTACCACAAGTATAAGAGATAAGATGAAAGAAAGAATAATGCACTTTTTTAGACTTG
ATATAGTTCCAATAGATAATAGTAACACCAGTTATATGTTTAATAAGTGTAATACCTCAGTCATTACACA
GGCCTGTCCAAAGGTATCCTTTGAACCAATTCCCATACATTATTGTGCCCCGGCTGGTTTTGCGATTCTA
AAGTGTAATGATAAGAAGTTCAATGGAACAGGACCATGTAAGAATGTCAGCACAGTACAATGTACACATG
GAATTAGGCCAGTAGTATCAACTCAACTGCTGTTAAATGGCAGTTTAGCAGAAGAAGAGAAAGTAATTAG
ATCTGAAAATTTCACAGACAATACTAAAACCATAAATAGTGATCTGAACGAATCTATACAAATTAATTGT
ACAAGACCCAACAACAATACAAGAAGAAAAAGCATACATATAGGACCAAGAAGAGCTTATGCAACAGGAG
AAATAATAGGAGATATAAGACAAGCACATTGTACCTTAGTAGAGAAAAATGGAATAACAACGTTAAAACA
GATAGTTAAAAAATTAAGAGTACAATTTGAAATAAAACAATAGTCTTTAATCAATCTTCAGGAAGGGGAC
CCAGAAATTGTAAGCACAGCTTTTAATTGTGGAGGGGGAATTTTTCTACTGTAATAAACAGCACTGTTTA
ATAGTACTTGGAATAGTAATAGTACTGAATGGTCAAATGACACTGAAAGCAATGACACAGTGATTACACT
CCCATGCAGAATAAAACAAATAGTAAACATGTGGCAGGAAGTTGGAAAAGCAATGTATGCCCCCTCCATC
AAGGGACAAATTAAGTGGATATCAAATATTACAGGGATACTATTAACAAGAGATGGGGGAAGAGATGAGG
TTAATAGCACGAACGAGAAACAAGAACCGAGATCTTCAGACCTGCAGGAAATATGAAGGACCAATTGGAG
AAGTGAATTATATAAATATAAAGTAGTAAAAATTGAACCATTAGGAATAGCACCCACTAGGGCAAGAAGA
AGAGTGGTGCAGAGAGAAAAAAGCAGCAGTGACACTAGGAGCTTTGTTCTTGGGTTCTTGGGAGCAGCAG
GAAGCACT
<U-065_3c1;PRT/1;HIV-1>
NASEKLWVTVYYGPVWKEANTTFCASDAKAYDTEVHNVWATHACVPTCDPRPQEDVLLGNVTENFNMWKN
NMVEQMHEDIISLWDQSLKPCVKLTPLCVTNCTNLNDTNISSSNVSCTHNSSGIGEMKNCSFNVTTSIRD
KMKKEYALFYRLDIVPIDNSNTSTMLISCNTSVIIQACPKVSFEPIPCIHYCAPAGFAILCNDKKFNGTG
PCKNVSTVQCTHGIRPVVSTQLLLNGSLAEEEIVIRSENFIDNTKTIIVHLNESIQINCTRPNNNTRKSI
HIGPGRAFYATGEIIGDIRQAHCNLSRAKWNNTLKQIVKKLRVQFENKTIVFNQSSGGDPEIVMHSFNCG
GEFFYCNTTALFNSTWNSNSTEWSNDTESNDTVITLPCRIKQIVNMWQEVGKAMYAPPIKGQIKWISNIT
GILLTRDGGRDEVNSTNENKTEIFRPAGGNMKDNWRSELYKYKVVKIEPLGIAPTRARRRVVQREKR
<U-074c12;DNA;HIV-1>
AGAAGAGCAGAAGACAGGCGGCAATGAGAGTGAAGGAGATCAAGAAGAATTGTCAGCGCTTGTGGAGATG
GGGCATCATGCTGCTCCTTGGGATTGATGATCTGTAGTGCTACAGAAAATTGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGGAAGGAAGCAAACACCACTCTATTTTGTGCATCTGATGCTAAAGCATATGATACAG
AGGTACATAATGTTTGGGCAACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTAAGATTAAA
AAATGTGACAGAAAATTTTAACATGTGGAGGAATAACATGGTAGAACAGATGCAGGAGGATATAATCAGT
TTGTGGGATCAAAGCTAAAGCCATGTGTAACATTAACTCCCACTATGTGTTACTTTAAATTGCACTGATT
ATTGGGGCAATGTTACTGGGACCAATACTACTAGTAACCCCTACTGGTACTGGTGTGGTGGTACCACTAA
CAATGGCGCGGAAGTGATGAAGTGCTCTTTTAAGTCACCCACAAGTGTAAGAGATAAGGTACAAAAAGAA
TCTGCTCTTTTTTATAGACTTGATATGTAGTAAAAATAGATGAGAAACAAATACAACAATTATAGGTTGA
TAAGTTGTAACACCTCAGTCATTAAACAGGCCCGTCCAAAGGTAAACTTTGAGCCAATTCCCATACATTA
TTGTGCCCCGGCTGGTTTGCGATTCTAAAGTGTAATGATAAGAAGTTCAATGGAACAAGGATCATGTAAA
AATGTCAGCACAGTACAATGTACACATGGAATTAAGCCAGTAGTATCCACTCACTTGCTGTTAAATGGCA
GTCTAGCAGAAGATGAGATAGTAATTAGATCTGAAAATTTCACGAACAATGCTAAAACCATAATAGTACA
GCTGAATAATTATGTAAAATTAATTGTATAAGACCCAATAATAATAACAAGAAAAGCTATATCACTCGGA
CCAGGAAGAAGCATTTATACAACAGGAGACATAATGCAAAAATATAGACAAGCACATTGCAACCTTAGTG
GTACAGAATGGAATAACACTTTAAAACAGGTAGCTAACAAATTAAGAGAACAATTTAACAAAACAATAAT
AAAATTTAAGCAACCCCCCCCGGGAGGGGACCTAGAATCACAATGCTACACTTTTAATTGTGGAGGAGAA
TTTTTTTTACTAATTCATCAGCACTGTTTATATATACTTTGACTTGGGATAGGTAAGGCATGGGCAAATA
CACTTGAAGGAAAATATCACACTCCATGCAGAATAAAACAAATTGTAAACAAGTGGCAGGAAGTAGGAAA
AGCAATATATGCCCCTCCCATCAGTGGACAGATTAATTGTACATCAAATATTACAGGGATACTATTAACA
AGAGATGGTGGTAACAACGACACTAACAACACTGAGGTCTTCAGACCTGGAGGAGGAGGAGATATGAGGG
ACAATTGGAGAAGTGAGTTATATAAATATAAAGTAGTAAAAATTGAACCATTAGGAATAGCACCCACCAG
GGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCAGCAATAGGAGCTATGTTCCTTGGGTTCTTGGGA
GCAGCAGGAAGCACT
<U-074c12;PRT/1;HIV-1>
SATEKLWVTVYYGVPVWKEANTTLFCASDKAYADTEVHNVAWATHACVPTDPNPQEVRLKVTENFNMWRN
NMVEQMQEDIISLWDQSLKPCVTLTPLCVTLNCTDYWGNVTGINTTSNPIGTGVGGTTNNGAEVMKCSFN
VTTSVRDKVQKESALFYRLDVVKIDEKTNTTNYRLISCNTSVIKQARPKVNFEPIPIHYCAPAGFAILKC
NDKKFNGTGSCKNVSTVQCHGIKPVVSTHLLLLNGSLAEDEIVIRSENFTNNAKTIIVQLNNYVKINCIR
PNNNTRKSISLGPGRAFYTTGDIIGNIRQAHCNNLSGTEWNNTLKQVANLREQFNKTIIKFKQPPPGGDL
EITMLTFCGGEFFYCNSSALFNSTLTWD&KAWANTLEENITLPCRIKQIVNSKWQEVGKAIYAPPISGQI
NCTSNITGILLTRDGGNNNDTNNTEVFRPGGGDMRDNWRSELYKYKVVKIEPLGIAPTRAKRRVVQREKR
<U-093c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGATGATGGAGATCAGGAAGAITATCAGAACTTATGGAGAGG
GGGCACCTTGCTCCTTGGGATGTTAATGATGATCTGTAGTGCTGCAGAAGAATCGTGGGTCACAGTATAT
TATGGGGTACCTGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATCAGATGCTAAAGGCTATGATA
CAGAAAGACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAATTGAATT
GGTAAATGTGACAGAATATTTTAACATGGGAAAAAATAACATGGTAGAACAGATGCATGAGGATATAATC
AGTTTATGGGATGAAAGCCTAAAGCCATGTGTAAAAATTAACCCCACTCTGGTTACTCTAAATTGCACTA
ATTTGAATATTACTAATACCACTGGTATTACTAATAGTAGCCTGGAAGAAATGAGGAGAATAATGACAAA
CTGTTCTTTCAAGGTCACCACAAATATAAGAGATAAGGTGCAGAAGCAATATGCACTGTTGTATAAACTT
GATGTAGTACAAATAGATGATGAGAGTACCACAAGGTAATAGGAGTAACACGCCTACAGGTTGATAAGTT
GTAACACCTCAGTCATTCACACAGGCCGTCCAAAGGTATCTTTGAGCCAAATTCCCATACACTTTTGTGC
CCCGGCTGGTTTTGCGATTCTAAAATGTAAGGATAAGAAGTTCAATGGAACAGGACTATGTAAAAATGTC
AGCACAGTACAATGTACACATGGAATTAGGCCAGTAGTATCAACTCAGCTGCTGTTAAATGGCAGTCTAG
CAGAAGAAGAGGTAGTAATTAGATCTGTAAATTTCACAAACAATGCTAAAACTATAATAGTACAGCTGAA
CAAATCTATAGAAATTAATTGTACAAGACCCAACAACAATACAAGAAGAGGTATAAATATAGGACCCGGG
AGAGCATTTTACACAATAAAGGACATAACAGGAGATATAAGACAAGCACATTGTAACATTAGTGCATCAT
ACTGGAATAATACTGTAACACAGGTAGTTGCAAAATTAAAAGAGCAATTTGGGAATAAAACAATAGTCTT
TAATCAATCCTCAGGAGGAGACCCAGAAATTATAATGCACACTTTTAATTGTGGAGGGGAATTTTTCTAC
TGTAAGACAACACAACTGTTTAATAGTACTTGGCCTAATAATGGTACTTGGCCTAATAGTAATTGGACTG
ATAATAATAGAACTTGGAACGGTGCTAAAGGAACTATCACACTCCCATGCAGAATAAAACAAATTGTAAA
CATGTGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATCGAAGGAAAATAAAAATGTACATCAAAT
CTTACAGGATTGCTATTAACAAGAGATGGTGGTAATGTGAATGGCACCACCATCGAGACCTTCAGACCTG
GAAGGAGGAGATATGAGGGACAATTGGAGAATGAATTATATAAATATAAAGTAGTACAAATTGAACCATT
AGGACTGGCACCTACCAAGGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAGGGGAGTAATAGGGAGCTATG
TTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-093c1;PRT/1;HIV-1>
SAAEESWVTVYYGVPVWKEATTTLFCASDAKGYDTERHNVWATHACVPTDPDNPQEIEVNVTEYFNMGKN
NMVEQMHEDIISLWDESLKPCVRLTPLCVTLNCTNLNITNTTGITNSSLEEMRRIMTNCSFKVTTNIRDK
VQKQYALLYKLDVVQIDDESTTGMRSNSAYRLISCNTSVITQARPKVSFEPIPIHFCAPAGFAILKCKDK
KFNGTGLCKNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSVNFNNAKTIIVQLMLKSIEINCTRPNN
NTRRGINIGPGRAFYTIKDITGDIRQAHCNISASDWNNTVTQVVALRKEQDFGNTIVFNQSSGGDPEIIM
HTFNCGGEFFYCKTTQLFNSTWPNNGTWPNSNWTDNNRTWNGAKGTITLPCRIKQIVNMWQEVGKAMYAP
PIEGKIKCTSNLTGLLLTRDGGNVNGTTIETFRPGGGDMRDNWRSELYKYKVVQIEPLGLAPTKAKRRVV
QREKR
<U-106c4;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGATGGAGATCAGGAGGAATTATCAGCGCTCGTGGAGATG
GGGCACCATGCTCCTTGGGATGTTGATGATTTATAGTGCTGCAGGAGAGTTATGGGTCACAGTTTATTAT
GGGGTACCGGTGTGGAAAGAAGCAACCACTACTTTATTCTGTGCATCAGATGCTAAAGCATATGACACAG
AGGTACATAATGTTTGGGCAACACATGCCTGTGTACCCACAGACCCTAATCCACAAGAAGTATTATTGGA
AAATGTGACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGATATAATCAGT
CTATGGGATCAAAGCTAAAGCCACGTGTAAAATTAACCCCAACTCTGTGTTACTTTAAACTGTACTAATT
TGAGAAATGTTACTAATTTGAAAAATGTTACTAATAACAGTAATATTAGTGGTACTAATAACAATACTAG
TAGTGGGGGGCTGAAGGGAGGAGAAATGAAAATTGCTCTTTTCTATATCACCACACACAGAAAGGATAAG
GTGAAGAAAGAATATGCACTTTTTTATAACCTTGATATAGTATCAACAGATGATGATAATACAAGCTATA
TATTGAGAAGTTGTAACACCTCAGTCATTACCCAGGCCTGTCCAAAGGTAACCTTTGAACCAATTCCCAT
ACATTATTGTACCCCAGCTGGTTTTGCGATTCTGAAGTGTAACGATAAGAAGTTCAATGGAACAGGACCA
TGTAGAAATGTCAGTACAGTACAATGTACACATGGAATCAAGCCAGTAGTGTCAACCCAACTGTTGTTAA
ATGGCAGTCTAGCAGAAGAAGAGGTAGTAATTAGATCTGAAAATTTCACGGACAATGTTAAAACCATAAT
AGTACAGCTGAATGAATCTGTAATAATTAATTGTACAAGACCCAGCAACAATACAAGAAAAAGTATACGT
TTTGGACCAGGGGCGGCATTTTATACAACAGGAGACATAATAGGAGATATAAGACAAGCACATTGTAACA
TCAGTAGAGCAGAATGGAATAACACTTTAAAACAAATAGTTAAAAAATTACAAGAACAATTTGTGAATAA
AACAATAGTCTTTAATCAATCTGCAGGAGGGGACCCAGAAATTGTAAGGCACAGTGTAAATTGTGGAGGG
GAATTTTTCTACTGCGATACAACACAACTGTTTAATAGTACTTGGAATAGTACTGGAGAGTCAAATAACA
CTCAAGAAAATGACCTAATCACACTCCCATGCAGAATAAAACAAATTATAAACAGATGGCAGGAAATAGG
AAAAGCAATGTATGCCCCTCCCATCCAAGGACAAATTAGCTGTACATCAAATATTACAGGGCTGCTACTA
ACAAGAGATGGTGGTAATAATAATAACAGCACAGAGACCTTCAGACCTGGAGGAGGAAATATGAAGGACA
ATTGGAGAAGTGAATTATATAAATATAAAGTAGTAAAAATTCAGCCATTAGGGGTAGCACCCACCAAGGC
AAAGAGAAGAGTGGTGCAGAGGGAAAAGAGCAGTGGGAGCACTAGGAGCTATGTTCCTTGGGTTCTTGGG
AGCAGCAGGAAGCACT
<U-106c4;PRT/1;HIV-1>
SAAGELWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHACCVPTDPNPQEVLENVTENFNMWKN
NMVEQMHEDIISLWDQSLKPRVKLTPLCVTLNCTNLRNVTKLKNVINNSNISGTNNNTSSGGLKGGEMKN
CSFYITTHRKDKVKKKEYALFYNLDIVSTDDNTSYILRSCNTSVITQACPKVTFEPIPIHYCTPAGFAIL
KCNDKKFNGTGPCRNVSTVQCTHGIKPVVSTQLLLNGSLAEEEVVIRSENFTDNVRTIIVQLNESVIINC
TRPSNNTRKSIRFGPGAAFYTTGDIIGDIRQARCNISRAEWNNTLKQIVKKLQEQFVNKIIVFNQSAGGD
PEIVRHSVNCGGEFFYCDTTQLFNSTWNSTGESNNTQENDLITLPCRIKQIINRWQEIGKAMYAPPIQGQ
ISCTSNITGLLLTRDGGNNNNSTETFRPGGNMKDNWRSELYKYKVVVKIQPLGVAPTKAKRRVVQREKS
<U-117c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGCAATAGAGAGTGACGGGGATGAGGAACAATTATCCGCACTTATGGAAAGA
GGTCACCTTCTCCTTGGAATATTGATGATATGTAGTGCTACAAGAAAATTTGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGGAAAGAAGCAACCACCACTCTATTCTGTGCATCGGATGCTAAGGCATATGATACAG
AGGCACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAATGAGATTGGA
AAATGTGACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCAGGATGATATAATCAGT
TTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCACTCTGTGTTACTTTAAATTGCACTAATA
CCACAAATGCTAATAGTACCAATAATAATAACTGGGACATGAAAAACTGCTCTTTCAATGTCACCTCAGG
CATAAGAGATAAGGTGCGAAAAGAACATGCACTCTTTTATGCACTTGATGTAGTACCAATAGATAATGAG
ACTAACTATAGGTTGATAAGTTGTAACACCTCAGTCATCACACAGGCCTGTCCAAAGGTATCCTTTGAGC
CAATTCCTATACATTATTATGCCCCGGCTGGTTTTGCGATTCTAAAATGTAGGGATAAAAAGTTCAATGG
AACAGGACCATGTAAAGATGTCAGCACAGTACAATGTACACATGGAATTAAGCCAGTAGTATCAACTCAA
CTACTGTTAAATGGCAGTCTAGCAGAAGAAGAGGTAGTAATCAGATCTGAAAACTTCACGAACAATGCTA
AAACCATATTAGTACAACTGAATGAATCTGTAGTAATTAATTGTACAAGACCCAACAACAATACAAGAAA
AAGTATAAATATAGGACCAGGGAGAGCATTCTATCAACAGGAGAAATAATAGGAGATATAAGAACAAGCA
CATTGTAACCTTAGTAAGGCACAATGGAACAACACTTTAAAAAAGGTAGTTGTAAAATTAAGAGAACAAT
TTCCGAATAAAACGATAGTCTTTACTCATTCCTCAGGAGGGGACCCAGAAATTGTAATGCACAGTTTTAA
TTGTGGAGGAGAATTTTCTACTGTAATTCAACCACCACTGTTTAATAGTACTTGGAAGTTGAATGGTACT
ATGGAATCAAATGACACTGAAGAGAAACTCACACTCCAATGCAGAATAAAACAAATCATGAACAAGTGGC
AGGAAGTAGGAAAGGCAATGTATGCCCCTCCCATCCAAGGACAGATTAGATGTTCATCAAATATTACAGG
GCTGTTATTAGTAAGAGATGGTGGGGGTCAACAGCGCCAACGAGACCTTCAGACCAGGAGGAGGAGTATG
AGGGACAATTGGAGAAGTGAATTATATAAATATAAAGTAGTAAAAATTGAACCATTAGGAATAGCACCCA
CCAAGGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCAGTGGGAATAGGAGCTTTGTTCCTTGGGTT
CTTGGGAGCAGCAGGAAGCACT
<U-117c1;PRT/1;HIV-1>
SATENLWVIVYYGVPVWKEATTTLFCASDAKAYDTEAHNVVWATHACVPTDPNPQERLENVTENFNMWKN
NMVEQMQDDIISLWDQSLKPCVKLTPLCVTLNCTNTTNANSTNNNNWDMKNCSFNVTSGIRDKVRKEHAL
FYALDVVPIDNETNYRLISCNTSVITQACPKVSFEPIPIHYYAPAGFAILKCRDKKFNGTGPCKDVSTVQ
CTHGIKPVVSTQLLLNGSLAEEEVVIRSENFINNAKTILVQLNESVVINCTRPNNNTRKSINIGPGRAFY
ATGEIIGDIRQAHCNLSKAQWNNTLKKVVVKLREQFPNKTIVFTHSSGGDPEIVMHSFNCGGEFFYCNST
PLFNSTWKLNGTMESNDTEGNLTLQCRIKQIMNKWQEVVKAMYAPPIQGQIRCSSNITGLLLVRDGGVNS
ANETFRPGGGDMRDNWRSELYKYKVVKIEPLGIAPTKAKRRVVQREKR
<U-124_2c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGCGAAGGGGATCAGGAGGAATTGGCAGCGCTTGTGTTGGAG
ATGGGGCACGATGCTGTCCTTGGAATGTTAATGATCTGTAGTGCTACAGAACATTGTGGGTACAGTCTAT
TATGGGGTACCTGTGTGGAAAGAAGCAACCACCACTCTATTTCGTGCATCAGATGCTAAAGCATATGGTA
CAGAGGTACATAATGTTTGGGCCACGCATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTAGTATT
GGAAAATGTAACAGAAAATTTTAATGCGTGGGAAAATAACATGGTGGAACAAATGCATGAGGATATAATC
AGTTTATGGGATCAAAGTCTAAAGCCATGTGTAAAGTTAACCCCACTCTGTGTTACTTTAAAATGCACTG
ATAATTTGGGGAATGATACTAAAACCAGTAATAAGAGCTGGGAAAAGATGGAGCCAGGAGAAATAAAAAA
CTGCTCCTTCAACATCACCACAAGCATAGGAGATAAGACGCAGGAAACATATGCATTTTTTTATAAACTT
GATGTAGTACCAATAGATAATAAGACTACAATAGATAATAATACTGCAAGAAACTATAGCGACTATAGGT
TGATAAGTTGTAACACCTCAGTCATTACACAGGCCTGTCCAAAGGTATCTTTTGAACCAATTCCCATACA
TTATTGTGCCCCGGCTGGTTTTGCGATTCTAAAGTGTAACAATAAGACATTCATGGGAAAAGGACCATGT
ACAAATGTCAGCACAGTACAATGTACACATGGAATTAAGCCAGTAGTATCAACTCAACTGCTGTTAAATG
GCAGTCTGGCAGAAGAAGAGATAATAATTAGATCTGAAAAATTTCACGGACAATGCTAAAACCTTATAAT
ACATCTGAACCACTCTGTAGAAATTAAGTGTATAAGACCCAACAACAATACAAGCGAAGGTATACATATA
GGACCAGGGAGAGCGTTTTATCCAACAAGAATAATAGGAGATATAAGAAAAGCACATTGTAACATTAATG
AAAACAGCATGGAAGAAGACAACCTTTAGCACAGATAGTTACAAAAGAGAACAATTTGGGAATAAACAAT
AGTCTTTAGCCAATCCTCAGGAGGGGACCCAGAAATTGTAATGCACAGTTTTAATTGTGGAGGGGAATTT
TTCTACTGTGATACAACAAAACTGTTTAATAGTACTTGGAATGATTAATGATACTTGGAATGGTGCTGAG
GGTCAAACAGCACTGAAAGAAACACCACCATCATACCTCCCATGCAAAATAAACAAATTATAAACTTGTG
GCAGGAGGTAGGAAAAGCAATGTATGCCCCTCCATCAAAGGAACTAATTAGATGTTCATCAAATATTACA
GGGCTGCTATTAACAAGAGATGGTGGTAATAACAATGACACAAACGGGACAGAGATCTTCAGACCTGGGG
GAGGAGATATGAGGGACAATTGGAGAAGTGAATTATATAAATATAAAGTAGTGAAAATTGAACCATTAGG
AGTAGCACCCACTAAGGCAAAGAGAAGAGTGGTGCAGAGAGAAAGAAGAGCAGTGGGAATAGGAGCTTTG
TTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-124_2c1;PRT/1;HIV-1>
SATEPLWVIVYYGVPVWKEATTTLFRASDAKAYGTEFVHNVWATHCVPDPNPQEVVLENVTENFNFAWEN
NMVEQMHEDIISLWDQSLKPCVKLTPLCVTLKCTDNLGNDTKTSNKSWEKMEPGEIKNCSFNITTSIGDK
TQKIYAFFYKLDVVPIDMKTTIDNNTARNYSDYRLISCNISVITQACPKVSFEPIPIHYCAPAGFAILKC
NNKTFMGKGPCTMVSTVQCTHGIKPVVSTQLLLNGSLAEEEIIIRSENFILNSKTLIIHLNHSVEIKCIR
PNNNTSEGIHIGPGRAFYPIPIIGDIRKAHCNINETAWKTTLAQIVTKLREQFGNKITVFSQSSGGDPEI
VMHSFNCGGEFFYCDTTKLFNLTWNVNDTWNGAGGSNSTERNITILLPCRIKQIINLWQEVGKAMYAPPI
KGLIRCSSNITGLLLTRDGGNNNDTNGTEIFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKAKRRVVQ
RERR
<U-145c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGGATCAGGAAGAATTGTCAGCTCTTGTGGAAATG
GGGCACCATGCTCCTTGGGATGTTGTGATCTGTTACTGCTGCAGAACAACTGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGGAAAGATGCAACCACCACTTTATTTTGTGCATCAGATGCTAAAGCATACGACAAAG
AGGCACATAATGTTTGGGCCACACATGCCTGTGTACCACAGACCCTAACCCACGAGAGAAATAAATTGGA
AAATGTGACAGAAAATTTTAACATGTGGAAAAATGACATGGGCAGACCAGATGCATAGAGGATAATCAGT
TTATGGGATCAAAGCCTAAAGCCATGTGTAGAATTAACCCACTCTGTGTTACTTTAAAATTGCACTAATA
TTAGTTTAATAGTACTAACAATGATACTATTAACAGTATAGTAGTAATACTGAAGGAATAAATATGAGGA
AGAAATGAAAACTGCTCTTTCAATACCACCACAAGTATAGGAGATAAAGAATAAGAGAGAATATGCACTT
TTTTATAAACTTGATGTAGTACCAATAGATAATAAGACAAGCTATACGTTGATAAATTGTAACACCTCAG
TCATTAAACAGGCCTGTCCAAAGGTAACCTTTGAACCAATTCCCATACATTATTGTGCCCCGGCTGGTTT
TGCGATTCTAAAGTGTCTCAATAAGACGTTCGATGGAAATGGAACATGTACAAATGTCAGCACAGTACAG
TGTACACATGGCATTAGACCAGTAGTGTCAACCCAACTACTGTTAAATGGCAGTCTAGCAGAAGAAGAGG
TAGTAATTAGATATGAGAATGTCCAGGACAATACTAAAACCATAATAGTACAGCTGAACGAAACTGTAAA
AATTAATTGTACAAGACCCAACAACAATAACAAGAAAAAGGTATCATGGGATGGGGGGAGACCAATTTAT
GCAACAGGAGAAATAATAGGAGATATAAGACAAGCACATCGTAATCTAAGTAAAAAAGACTGGGGAGACA
CTTTAAAGAAGATAGCTATAAAACTACAAGAACAATTAATACAACAATAATCTTTTGAGCAATCCTCAGG
AGGGGACCCAGAAATTACAATGCACAGTCTTAATTGTGGAGGGGAATTTTTCTACTGTAATACATCAAAG
CTGTTTAATGGCACTTGGTCTAATGGTACTTGGACTAGTPGGTATTTGGAATAATACTGGAGAGTCAGTA
GCACAATCACACTCCCATGCAGAATAAAACAAATTATAAACAGGTGGCAGGGAGTAGGACAAGCAATGTA
TAACCCTCCCATCAACGGACTATTAGCTGTTCATCAAAATATTACAGGACTGATATTAACAAGAGATGGA
GGTAACAACAGGTCCAACGAGACCTTCAGACCAAGTGGAGGAAACATGAGGGACAATTGGAGAAGTGAAT
TATATAAATATAGAGTAGTAAAAATTGAACCATTAGGAGTAGCACCCACCAAGGCAAAGAGAAGAGTGGT
GCAGAGAGAAAAAAGAGCAGTGGGGATGATAGGAGCTGTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGC
ACT
<U-145c1;PRT/1;HIV-1>
SAAEQLWVTVYYGVPVWKDATTTLFCASDAKAYDKEAHNVWATHACVPTDPKNPREIKLENVTEFNMWKN
DMADQMHEDIISLWDQSLKPCVELTPLCVTLNCTNISLNSTNNDTINSSNSTEGINMREEMKNCSFNTTT
SIGDKNKREYALFYKLDVVPIDNKTSYTLINCNTSVIKQACPKVTFEPIPIHYCAPAGFAILKCLNKTFD
GNGTCTNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRYENVQDNTKTIIVQLNETVKINCTRPNNNTR
KGIHVGWGRPIYATGEIIGDIRQAHRNLSKKDWGDTLKKIAIKLQEQFNTTIIFEQSSGGDPEITMHSLN
CGGEFFYCNTSKLFNGTWSNGTWTSGIWNNTGESDSTITLPCRIKQIINRWQGVGQAMYNPPINGLISCS
SNITGLILTRDGGNNRSNETFRPSGGNMRDNWRSELYKYRVVKIEPLGVAPTKAKRRVVQREKR
<U-171c11;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGGATCAGGAAGAACTATCAGCACTTGTGGAAATG
GGGCACCTTGCTCCTTGGGATATCGATGATCTGTAGTGCTAAAGAAGACAAGTTGTGGGTCACAGTCTAT
TATGGGGTACCTGTGTGGAGAGATGCAAACACCACTCTATTTTGTGCATCAGGTGCTAAAGCATATAAGA
CAGAGGTACATAATGTCTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTGGTATT
GGGAAATGTGACAGAATATTTTAATGCATGGAAAAATGACATGGTAGAACAGATGCATGAGGATATAATC
AATCTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCACTCTGTGTCACTTTAAATTGCACTA
ACGTTAAAAACAATGCTACCAAAATAAATGATCACCACTACACCTAGTGAGGAAATAGAAATAAAAAAAA
CTGCTCTTTCAACATCACCGCAGGCATAAGAGATAAGATACAGAAAGAATATGCATTGTTTTCTAAATTT
GATTTAGTACAAATCCATGAAGATAATAAAAATAATAATAATACAAACTATACAGACTATAGGTTGATAA
GTTGTAACACCTCAGTCATTACGCAGGCCTGTCCAAAAGTATCCTTTGAGCCAATTCCCATACATTTTTG
TACCCCGGCTGGTTTTGCGATTCTAAAGCGTAATAATAAGACATTCAACGGAAAAGGGCCATGTACAAAT
GTCAGTACAGTACAGTGTACACATGGAATTAGGCCAGTAGTATCAACTCAACTGCTGCTAAATGGCAGTT
TAGCAGAAGAGGATGTAGTAATTAGATCTGAAAATTTCACAAACAATGTTAAAACCATAATAGTACAGCT
GAAAGAAGCTGTACAAATTAATTGCACAAGGCCCAACAACAATACAAGAAAAAGTATACCTATAGGACCA
GGGAGAGCATTTTATGCAACAGGAGACATAATAGGAGATATAAGACAAGCACATTGTAACATTAGTGGAA
CACAATGGAATAAAACTTTAGGAAAGATAGTTGAAAAATTAAAAAGAACAATTTGGGAATAAACAATAAT
CTTTAACCAACCCGTAGGGAGGGGACCCAGAAATTGTAGCGCGCACACTTTAATTGTGGAGGGAATTTTC
TACTGTAATACAACACCTCTGTTTAATAGTACCTGGACTTGGAATAGTACTTGGAATGGTACTACAAGTA
CTGGGAATGTTCCTAAAAAAATTATCACACTCCAATGCAGAATAAGACAAATTGTAAACATGTGGCAGAA
AGTAGGAAAAGCAATGTATGCCCCTCCCATCAGAGGACAGATTGGATGTTCATCAAATATTACAGGGCTG
CTATTAACAAGAGATGGTGGTAATAGTGAGAACGGGACCAATAACACAGACACAGAGACCTTCAGACCGG
GAGGAGGAGATATGAGGGACAATTGGAGAAGTGAATTATATAAATATAAAGTAGTAAGAATTGAACCATT
AGGAATAGCACCCACTAAGGCAAGGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCAGTGGGAATAGGGGCT
TTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-171c11;PRT/1;HIV-1>
SAKEDKLWVTVYYGVPVWRDANTTLFCASGAKAYKTEVHNVWATHACVPTDPNPQEVVLGNVTEYFNAWK
NDMVEQMHEDILNLWDQSLKPCVKLTPLCVTLNCTNVKNNATKINDTTTTPSEEIEIKNCSFNITAGIRD
KIQKEYALFSKFDLVQIHEDNKNNNNTNYTDYRLISCNTSVITQACPKVSFEPIPIHFCTPAGFAILKRN
NKIFNGKGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEEDVVIRSENFTNNVKTIIVQLKEAVQINCTRP
NNNTRKSIPIGPGRAFYATGDIIGDIRQRAHCHISGTQWNKTLGKIVELKEQFGNKTIIFNQFVGGDPEI
VAHTFNCGGEFFYCNTTPLFNSTWLWNSTWNGTTSTGNVTKKIITLQCRIRQIVNMWQKVGKAMYAPPIR
GQIGCSSNITGLLLTRDGGNSENGTNNTDTETFRRPGGGDMRDNWRSELYKYKVVRIEPLGIAPIKARRV
VQREKR
<U-174c11;DNA;HIV-1>
AGAAAGACAGAAGACAGTGGCAATGAGAGCGAAGGGGACCAGGAAGAATTGTCAGCACTTGTGGTGGAGA
TGGGGCACCATGCTCTTTGGGATGTTGATGATCTGTAGTGCTGCAAAAGAAAAATTGTGGGTCACAGTCT
ATTATGGGGTGCCTGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATCAGATGCTAAAGCATATGA
CACAGAAGCACATAATGTTTGGGCCACACATGCTTGTGTACCCACAAACCCTAACCCACAAGAAGTATTA
TTGAAAAATGTGACAGAAGATTTTAACATGTGGAAATATATGGTAGAACAGATGCATGATGAGGATATAA
TCAGTTTATGGGATCAAAGCCTAAAGCCATGTGTGAAATTAACCCCACTCTGTCGTTACTTACATTGCAC
TGATGCGAACATTACTGCAAACAGTACTGCTACTAACAGTACTGTTAGCTCCATTAAAGAAGAAGTGAAA
AACTGCTCTTTCAATATCACCACAGAAGTAAGAGACAAGGTAAAGAAAGAACATGCACTTTTTTATAGAC
TTGATGTAGTACCAATAGCTAATGATAATACAAGCTATACATTGGTAAATTGTAACACCTCAACCATTAC
ACAGGCCTGCCAAAGGTGACCTTTGAACCAATTCCTTATACATTATTGTGCCCCGGCTGGTTTTGCGATT
CTAAAATCTAATGATAAGAATTTCAATGGAACAGGACCATGTAAAAATGTCAGCACAGTACAATGCACAC
ATGGAATTAGGCCAGTGGTGTCAACTCAACTACTGTTAAATGGCACTCTAGCAGAAGATGAGGTAGTAAT
TAGATCTGAAAATTTCAAACAATGCAAAAAATCATAATAGTACAGCTAAAATGAATCTGTAATAATTAAT
TATACAAGACCTGGCAACAATACAAGAAAAAGTATACATATAGGACCGGGAAGTGCATTTTATGCAACAG
GAGACATAATAGGAGATATAAGACAAGCACATTGTAACATTAGTAAAGCAGATTGGGAGAAAACACTAAA
ACAGGTAGTTAAAAAATTACAGGAACAATATGGAATAAAAACAATAAACTTTACCCAATCCTCAGGAGGA
GACCCAGAAATTGTAATGCACAGTCTTAATTGTGGAGGATAATTTTTCTATTGTAATACAACAAAGCTGT
TTAATAGTACTTGGCAGAATGGTACTATTGTAGGATCAGAAAATACGTCAGACATTATCATACTCCCATG
CAGAATAAAGCAAATTATAAACAGGTGGCAGGAAGTAGGAAAAGCAATGTATCGCCCTCCCATCAGCGGA
GACATTAGATGTACATCAAATATTACAGGGCTGCTATTAACAAGAGATGGGGGTATAAAGAACAAGACCA
ATGGGACAGAGACAGAGATCTTCAGACCTGCAGGAGGAGATATGAAGGAACAATTGGAGAAGTGAATTTA
TAAATATAAAGTAGTAAAAATTGAACCGTTAGGAATAGCAGGGACCAGGGCAAGGAGAAGAGTGGTGCAC
AGGGAAAAAAGAGAAGTGACGCTGGGAGTTATGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-174C11;PRT/1;HIV-1>
SAAKEELWVIVYYGVPVWKEATTTLFCASDAKAYDTEAHNVWATHACVPINPNPQEVLLKNVTEDFNMWK
NNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLHCTDANITANSTATNSTVSSIKEEVKNCSFNIITEVRD
KVKKEHALFYRLDVVPIANDNTSYTLVNCNTSTITQACPKVIFEPIPIHYCAPAGFAILKCNDKNFNGTG
PCKNVSTVQCTHGIRPVVSTQLLLNGSLAEDEVVIRSENFTNNAKIIIVQLNESVIINYYRPGNNTRKSI
HIGPGSAFYATGDIIGDIRQAHDNISKALWEKTKLKQVVKKLQEQYGNKTNFTQSSGGDPEIVMHSLNCG
GEFFYCNTTKLFNSTWQNGTIVGSENTSDIIILPCRIKQIINRWQEVGKAMYAPPISGDIRCTSNTTGLL
LTRDGGIKNKTNGTETEIFRPAGGDMKDNWRSELYKYKVVKIEPLGIAPTRARRRVVQREKR
<U-177c11;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAAAGTGAAGGGGACCAGGAAGAGTTATCAGCACTTGTGGAGATG
GGGCATCATGCCCCTTGGGATGTTGACGATTTGTAGTGTTGCACAACAATTGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGGAAAGAAGCCACCACCACTCTATTTTGTGCATCAGAAGCTAAGGCATATGTTACAG
AGGTACATAATATTTGGGCCACACATGCCTGTGTACCCTCAGACCCCAACCCACAAGAAGCAGTATTGGA
AAATGTGACAGAAAATTTTAACATATGGAAAAATGACATGGTAGACCAGATGCATGAGGATATAATCAGT
GTATGGGATCAAAGCCTAAAGCCATGTGTGAAATTAACCCCGCTCTGTGTCACTTTAAATTGCACTGATT
ATTTTGGGAAAACTAATATTACTACCACTTCTAGCAGTGGTCCCAATAATGATAGAGGAATGAAAAACTG
CTCTTTCAATATCACCACAAGCATAAGAGATAAGGTAACGAAAGAACATGCACTTTTTTATAGAGTTGAT
GTAGTCCCAATAGATAGTAGTAATAGTAGCTATAGATTGATAAATTGTAACACCTCAGTCATTACACAGG
CCAGTCCAAAAGTATCCTTTGAGCCAATTCCCATACATTATTGTACCCCGGCTGGTTTTGCGATTATAAA
GTGTAATAAGAAGACATTCAATGGAACAGGACCATGTAGAAATGTCAGCACAGTACAATGTACACATGGA
ATTAGGCCAATAGTGTCAACTCAGCTGTTGTTAAATGGCAGTCTAGCAGTAGAAGAGGTAGTAATTAGAT
CTGAAAATATCACGAACAATGCTAAAACCATAATAGTACAATTGAACGAATCTGTAAGCATCAATTGTAC
AAGACCCAGCAACAATACAAGAAGGGGGATACATATGGGACCAGGGAGAGCATTTTGGACAACAGGTGAA
GTAATAGGAGATATAAGGAAAGCACATTGTAACATTAGTAGAAAAGAATGGAATGACACTTTACACAAGG
TAGTCAAAAAATTAAGGGAAAAATTTAATGCAACAATAATCTTTAATCAATCCACAGGAGGGGACCCAGA
AATTGTAATGCACACTTTTAATTGTGGAGGGGAGTTTTTCTACTGTAACACATCACAACTGTTTAATAGT
ACTTGGGATATTAATGGAAATACTACTGGAGGGTTAGAAGGCAATGACACAATCACACTCCAATGTAGAA
TAAAACAAATTGTAAACATGTGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATCCAAGGAAAAAT
TAGATGTTCATCAAATATTACAGGGCTGCTATTAACAAGAGATGGTGGTAATAACAGTAGTAACAATGAG
ACCTTCAGACCTGGAGGAGGAGATATGAGGGACAATTGGAGAAGTGAAGTATATAAATATAAAGTAGTAA
AAATTCAACCACTAGGAATAGCACCCACCAAGGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCAGT
GGGAATAGGAGCTTTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-177c11;PRT/1;HIV-1>
SVAEQLWVTVYYGVPVWKEATTTLFCASEAKAYVTEVHNIWATHACVPTDPNPQEAVLENVTENFNIWKN
DMVDQMHEDIISVWDQSLKPCVKLTPLCVTLNCTDYFGKTNKTTTSSSGPNNDRGMKNCSFNITTSIRDK
VTKEHALFYRVDVVPIDSSNSSYRLINCNTSVITQASPKVSFEPIPIHYCTPAGFAIIKCNNKTFNGTGP
CRNVSTVQCTHGIRPIVSTQLLLNGSLAVEEVVIRSENITNNAKTIIVQLNESVSINCTRPSNNTRRGIH
MGPGRAFWTTGEVIGDIRKAHCNISRKEWNDTLDKVVKKLREKFNATIIFNQSTGGDPEIVMHTFNCGGE
FFYCNTSQLFNSTWDINGNTTGGLEGNDTITLQCRIKQIVNMWQEVGKAMYAPPIQGKIRCSSNITGLLL
TRDGGNNSSNNETFRPGGGDMRDNWRSELYKYKVVKIQPLGIAPTKAKRRVVQREKR
<U-218c14;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAGGGAGACCAGGAAGAATTATCAGCACTTGTGGAGATG
GGGCAACATATGGAGATGGGGCATGATGCTCCTTGGGATGTTGATGATCTGTAGTGCTGCAGAAGATTTG
TGGGTCACAGTTTATTATGGGGTACCTGTGTGGAAAGACGCAAAGACCACTCTATTTTGTGCATCAGATG
CTAAAGCATATAAGACAGAGGTACATAATGTTTGGGCCACGCATGCCTGTGTACCCACAGACCCCAACCC
ACAAGAAGTAGAAATGAAAAATGTGACAGAAGATTTTAACATGTGGAAAAATAATATGGTAGAACAGATG
CATGAGGATATAATCAGTTTATGGGATCAGAGCCTAAAACCACGTGTAAAATTAACCCCACTCTGTGTTA
CTTTAAAGTGCTTTGATGTGAAGAATAAAACCACTACTACCACTACTAATAGTACCACATCCACTATTAG
TACTACTACCACTAAGACGCCCACTGTTAGTAAAGGGACAGAGAAATCAGAACTGACAAACTGCTCTTTC
AATATCACCACAAACATAAGAGATAAGTTTCAGAAAAACTATGCAATTTTTGATAAACTTGATGTAGTAC
CAATAGATGATGATAATGATACTACTACTAACAATAATACTAGTAATGAAAAAAAGCTTTGGTTAATAAA
TTGTAACACCTCAGTCATCACACAGGCCTGCCCAAAGATATCATTTGAACCAATTCCCATACATTATTGT
ACCCCGGCTGGTTTTGCGATTCTAAAGTGTAAAGATAAAAATTTCAATGGAACAGGAAAATGTAAAAGCG
TCAGCACAGTGCAATCTACACATGGAATTAGGCCAGTAGTGTCAACTCAACTACTGTTAAATGGCAGTCT
AGCAGAAGAAGAGGTAGTAATTAGATCTGCCGATTCGTCGGACAATACTAAAATCATAATAGTACAGCTG
AATAAATCTGTAGAAATTAATTGTACAAGACCCAACAACAATAAAAGAAAAAGTATAAATATAGGACCAG
GGAGAGCAATGTTTGCAACAGGAGACATAATAGGAGATATAAGAAAAGCATCTTGTACCATTAATGAAAC
ACAATGGAATAACACTTACAACAGGTAGTTATAAAATTAAAAGAAACAATATGGAAATAAAACAATAGTC
TTTGACCGCCCCTCAGGAGGGGACCCAGAAATTGTAATGCACAGTTTTAATTGTGGAGGAGAATTTTTCT
ATTGTAATTCAACACAACTGTTTAATAGTAGTTGGGGGCCTAATGGTACTCGGAATGGTACTACAACGAT
AAATGGTACTATCATACTCCCATGTAGAATAAAACAAATTATAAACATGTGGCAGGAAGTAGGAAAAGCA
ATGTATGCCCCTCCCATCGAGGGACTTATTAACTGTACATCAAATATCACAGGGCTACTATTAACAAGAG
ATGGTGGCCATGACAATAATGACACAAAAAATAACAATACCGAGATCTTCAGACCTGGAGGAGGAGATAT
GAGGGACAATTGGAGAAGTGAATTATATAAATATAAAGTAGTAAAAATTGAACCATTAGGAATAGCACCC
AACAGGACAAAAAGAATAGTGGTGCAAAGAGAAAAAAGAGCAGTGGGATTCGGAGCTGTGTTCCTTGGGT
TCTTGGGAGCAGCAGGAAGCACT
<U-218c14;PRT/1;HIV-1>
SAAEDLWVTVYYGVPVWKDAKTILFCASDAKAYKTEVHNVWATHACVPTDRNPQEVEMKNVTEDFNMWKN
NMVEQMHEDIISLWDQSLKPQVKLTPCVTLKCFDVKNKTTTTTTTNSTTSTISTTTTKTPTVSKGTEKSE
LTNCSFNITTNIRDKFQKNYAIFDKLDVVPIDDDNDTTTNNNTSNEKSFRLINCNTSGIIQACPKISFEP
IPIHYCTPAGFAILKCKDKNFNGTGKCKSVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSADFSDNTK
IIIVQLNKSVEINCTRPNNNKPKSINIGPGRAMFATGDIIGDIRKASCTINETQWNNTLQQVVIKLKEQY
GNKTIVFDRPSGGDPEIVMHSFNCGGEFFYCNSTQLFNSSWGPNGTRNGTTTINGTIILPCPIKQIINMW
QEVGKAMYAPPIEGLINCTSNITGLLLIRDGGHDNNDTKNNNTEIFRPGGGDMRDNWRSELYKYKVVKIE
PLGIAPNRTKRIVVQREKR
<U-228c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAAAGTGAAGGGGATCAAGAAGAGTTATCAGCACTTGTTGAGATG
GGGCGCCATGCTCCTTGGGATGTTAATGATCTGTAGTGCTGCAGAACAATTGTGGGTCACAGTCTATTAT
GGGGTACCTGGTGTGGAGAGAAGCAAACACCACTCTATTTGTGCATCAGATGCTAAAGCATATGATAAAG
AGGTACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTAGAATTGGA
AAATGTGACAGAAAATTTTAACATGTGGAAAAATGACATGGTAGAACAGATGCATGAGGATATAATCAGT
TTATGGGATCAAAGCCCTAAAGCCATGTGTAAAATTAACCCCCTCTGCGTTACTTTAAATTGTACTGATT
TAAGGTCACAGAATGTGACTTATACCACTGGTGCTAATACCACTATGGCTACTACCACTAGTACTAATAC
CACTAGTATGGGGGAGAGATGCAGGTAGGAATGAAAAAACTGCTCTTTCAATATCACCACAAACACACAA
GATAAGGTGAAGGGATATGCACATTTTGATAACCTTGATCTAGTAACAAATAGAGGATGAAAACACAGCA
ATAACAGCTATAGGTTGATACATTGTAACACCTCAGTAATTACACAGGCCTGTCCAAAGGTATCCTTTGA
GCCAATTCCTATACATTATCGTGCCCCGGCTGGTTTTGCGATTCTAAAGTGTAAAGATAAGAAGTTCAAT
GGAACAGGACCCTGTACAAATGTCAGCACAGTACAGTGTACACATGGAATTAGGCCAGTAGTATCCACTC
AACTGCTGTTCAATGGCAGTCTAGCAGAAGAAGAGGTAGTAATTAGATCTGCCAATTTCTCAGAAAATGA
TAAAATCATAATAGTACAGCTGAAAGACGCTGTACAAATTAATTGTACAAGACCCAACAACAACACCAGA
AAAGGTATACAATATGGGACCAGGGAAAGTATTTTACGCAACAGAAGTCATAGGGACATAAGGCGAGCAC
ATTGTAACATTAGTAAAGAAAATTGGAATAATACTTTAAAACAGATAGCTATACAATTAAGAGAGCAAGA
GCAGTTCAAGAATAAAACAATAGTCTTTAATCAATCCTCAGGAGGGGACCCAGAAATTGTAATGTCTAGT
TTTAATTGTGGAGGGGAATTTTTCTACTGTAATACAACACAACTGTTTAATAGTACTTGGGAGAATGATA
CTAGTACTTGGAATGATACTGAAGGGTCGAATGGCACTATCACACTCCCATGCAGAATAAAACAAATTAT
CAACATGTGGCAGGAGGTAGGAAAAGCAATATATGCCCCTCCCATCAAAGGACCACTTCATTGTTCATCA
AATATTACAGGGCTACTATTAACAAGAGATGGTGGTAATACTAATGAGAGCAACACCACCGAGGTCGAGG
TCTTCAGACCTTTAGGAGGAAACATGAGGGACAATGGGAGAAGTGAATTATATAAATATAAAGTAGTAAA
GATTGAACCATTAGGAATAGCACCCACCAAGGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCAGTG
GGAATAGGAGCTGTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-228c1;PRT/1;HIV-1>
SAAEQLWVTVYYGVPVWREANTTLFCASDAKAYDKEVHNVWATHACVPTDPNPQEVELENVTENFNMWKN
DMVEQMHEDIISLWDQSLKPCVRLTPLCVTLNCTDLRSQNVTYTTGANTTMATTTSTNTTSSGGEMQVGM
KNCSGNITTNTQDKVKGYAHFDNLDLVQIEDENHSNNSYRLIHCNTSVITQACPKVSFEPIPIHYRAPAG
FAILKCKDKKFNGTGPCTNVSTVQCTHGIRPVVSTQLLFNGSLAEEEVVIRSANFSENDKIIIVQLKDAV
QINCTRPNNNTRKGIHMGPGKVFYATEVIGDIRRAHCNISKENWNNTLKQIAIQLREQEQFKNKTIVFNQ
SSGGDPEIVMSSFNCGGEFFYCNTTQLFNSTWENDTSTWNDTEGSNGTITLPCRIKQIINMWQEVGKAIY
APPIKGPLHCSSNITGLLLTRDGGNTNESNTTEVEVFRPLGGNMRDNWRSELYKYKVVKIEPLGIAPTKA
KRRVVQREKR
<U-241_2c2;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGGATCATGAAGAATTGTCAGCACTTGTGGTGGAG
ATGGGGGGCATGATGCTCCTTGGGATGTTGATGATCTGTAGTGCTACAACAATTGTGGGTCACAGTCTAT
TATGGGGTACCTGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATCAGATGCTAAAGCATATGACA
CAGAGGCACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCTAACCCACAAGAAGTAGAATT
GAAAAATGTGACAGAAAATCTTAACATGTGGAAAAATGACATGGTAGAACAGATGCATGAGGATATAATC
AATTTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACTCCACTCTGTGTCACTTTACATTGCACTA
ATTTGAATGTTACTACCAGTAATACTACAAGTTGGGGAGAGATGGAGGCAGGAGAAATAAAAAACTGCTC
TTTCAATGTCACCACACGCAGAAGAAATAAGAAAGAATATGCACTTTTTTATAAACTTGATGTAGTACCT
ATAGATAGTGATAATGCAAGCTATACGTTGATAAAATTGTAAACTTCAGTCATTACACAAGCCTGTCCAA
AGGTATCCTTTGAACCAATTCCCATACATTATTGTGCCCCGGCTGGTTTTGCGATTCTAAAATGTAATGA
TAAGAAATTCAATGGAACAGGACCATGTAAAAATGTTAGCACAGTACAATGTACACATGGAATTAGGCCA
GTAGTGTCAATTCAACTGCTGTTAAATGGCAGTCTAGCAGAAGAAGAGGTAGTAATTAGATCTGAAAATT
TCTCGAACAATGCTAAAGCCGTAATAGTACAGCTGAATGCATCTATAGAAATTAATTGTACAAGACCCAA
CAACAATACAAGAAAAGATATACATATAGGACCAGGGAGAGCATTATATACAACAGGAGGAATAATAGGA
GATATAAGACAAGCACATTGTAGCCTTAGGAAAGCAGAATGGAATGACACTTTAAAACATGTAGTTACAA
AATTAAGAGAACAATTTGGGAATAAAACAATATTCTTTAATCAATCCTCAGGAGGGGACCCAGAGATTGT
AATGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGTAATACAACAATGCTGTTTAATAGTAATAGT
ACTTGGAATGATACTACAGGACCAGATAATAACACTATCATACTCCCATGTAGAATAAAACAAATTATAA
ACAGGTGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCTATCAGTGGACCAATTAAACGCACATCAAA
TATTACAGGGCTACTATTAACAAGAGATGGTGGTAGTAACACCACCGAGACCTTCAGACCTGGAGGAGGA
GATATGAGGGACAATTGGAGAAGTGAATTATATAAATATAAAGTAGTAAAAAATTGAGCCATTAGGGTAG
CACCCACCAGGGCAAGGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCAGTGGGACTGGGAGCTGTATTCCT
TGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-241_2c2;PRT/1;HIV-1>
SATEQLWVTVYYGVPVWKEATTTLFCASDAKAYDTEAHNVWATHACVPTDPNPQEVELKNVTENLNMWKN
DMVEQMHEDIINLWDQSLKPCVKLTPLCVTLHCTNLNVTTSNTTSWGEMEAGEIKNCSFNVTTRRRNKKE
YALFYKLDVVPIDSDNASYTLINCNTSVITQACPKVSFEPIPIHYCAPAGFAILKCNDKKFNGTGPCKNV
STVQCTHGIRPVVSIQLLLNGSLAEEEVVIRSENFSNNAKAVIVQLNASIEINCTRPNNNTRKDIHIGPG
RALYTTGGIIGDIRQAHCSLRKAEWNDTLKHVVTKLREQFGNKTIFFNQSSGGDPEIVMHSFNCGGEFFY
CNTTMLFNSNSTWNDTTGPDNNTIITPCRIKQIINRWQEVGKAMYAPPISGPIKRTSNITGLLLTRDGGS
NTTETFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTRARRRVVQREKR
<U-242c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGAGATGAGGAAGCACTGGCAGCACTGGTGGACAGG
GGGCATCATGCTCCTTGGGATGCTGATGATCTGTAGTGCTGTAAACAACTTGTGGGTCACTGTATATTAT
GGAGTGCCTGTGTGGAGAGAAGCAACCACCACCCTATTTTGTGCATCAGATGCTAAAGCATACAAAACAG
AGGTACATAATGTCTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAGATAGAATTGGT
AAATGTGACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGATATAATCAGT
TTATGGGATCAAAGCCTAAAACCATGCGTAAAATTAACCCCACTCTGTGTTGTGAAAAACTGCTCTTTCA
ACACCACCACAATGGTAAGGGATAGGGAGCGGAAAGAATATGCTCTCTTTTATAAACTTGATGTAGTACA
AATGAATGATAATAATAATAATAGTACCCATGGAACCTATAGATTGATAAATTGTAATACCTCAGTCATT
ACACAGGCCTGTCCAAAGGTATCCTTTGAGCCAATTCCCATACATTATTGCGCCCCGGCTGGTTTTGCGA
TTCTAAAGTGTAAAGACAAGAAGTTCAATGGAACGGGACCATGCAAAAATGTCAGCACAGTACAGTGTAC
ACATGGAATTAGGCCAGTAGTGTCAACTCAACTGCTGCTAAATGGCAGTCTAGCAGAAGAAGAGGTAATA
ATTAGATCTGAAAACTTCACAAGCAATGCTAAAACCATAATAGTACAGCTAAATGAAACTGTAGAGATTA
ATTGCACAAGACCTAGCAACAATACAAGAAGAAGTATACATATAGACCAGGGAGAGCATTTTTACACAAC
AGGAGACATAATAGGAGATATAAGAAAAGCACATTGTAACTATAGTAGAACAAAATGGAATAACACTTTA
GGACAGATACTTGAAAAATTACAAGAACAATTTAAGAATAAAACAATAATCTTTAATTCATCCTCAGGAG
GGGACCCATAAATTGTATATCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGTAATACAACAGAACT
GTTCGATAGTACCTGGTATAGCCCCTGGAACAGTACTGGTGGGTCAAATAACACTGAAGGGAATAGCACG
ATCACACTCAAATGCAGAATAAAGCAAATTGTAAACAGGTGGCAGGAAGTAGGAAAAGCAATGTATGCCC
CTCCCATCCAAGGGAAAATTAAATGTTCATCAAATATTACAGGGCTACTATTAACAAGAGACGGTGGTAA
TAGTAATAGTAGTAACGAGACCTTCAGACCAGGAGGAGGAGACATGAGAGACAATTGGAGAAGTGAATTA
TATAAATATAAAGTAATAAAAATTGAACCATTAGGAGTAGCACCCACCAAGGCAAAGAGAAGAGTGGTGC
AAAGAGAAAGAAGAGCAGTGGGAACAATAGGAGCTATGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCAC
T
<U242c1;PRT/1;HIV-1>
SAVNNLWVTVYYGVPVWREATTTLFCASDAKAYKTEVHNVWATHACVPTDPNPQEIDLVNVTENFNMWKN
MMVEQMHEDIISLWDQSLKPCVKLTPLCVVKNCSFNTTTMVRDRERKEYALFYKLDVVQMNDNNNNSTHG
TYRLLNCNTSVITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGIGPCKNVSTVQCTHGIRPVVSTQL
LLNGSLAEEEVIIRSENFTSNAKTIIVQLNETVEINCTRPSNNTRRSIHIGPGRAFYTTGDIIGDIRKAH
CNISRTKWNNTLGQIVEKLQEQFKNKTIIFNSSSGGDPEIVYHSFNCGGEFFYCNTTELFDSTWYSPWNS
TGGSNNTEGNSTITLKCRIKQIVNRWQEVGKAMYAPPIQGKIKCSSNITGLLLTRDGGNSNSSNETFRPG
GGDMRDNWRSELYKYKVIKIEPLGVAPTKAKRRVVQRERR
<U-257c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGGATCAGGAAGAGTTATCAAAACTTGTGGAAATG
GGGCACATTGCTCCTTGGGATATTGATGATTAGTAGTGCTACAGAACAATTGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATCAGATGCTAAAGCCTATAATACAG
AGGTTCATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAATCCACAAGAAGTAATGTTAAA
TGTGACAGAGAATTTTTAACATGTGGAAAAATGACATGGTAGAAACAGATGAGGAGGATATAATCATTTA
TGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCACTCTGTGTTACTTTAAGCTACACTGATGCAA
ATAGTACTGATGTTAATCATACCAAAAAATAGTAGTGAGGGAATGATGGAGGGGAGAAAAATGAAAACTG
CTCTTTCAATATCACCACAAGCATGGGAAATAAGATGCAGAAAGAATATGCACTTTTTCATAGACTTGAT
GTAATACCAATGGATAATGAAAGTGCTAGTGCTAAATATTCTAACTATAGGTTAATAAGCTGTAACACCT
CAGTCACTACACAGGCTTGTCCAAAAATATCATTTGAGCCAATTCCCATACATTATTGTACCCCGGCTGG
TTTTGCGATTCTAAAATGTAATGATAAGAAATTCAGTGGAAAAGGAGGATGTAGAAATGTCAGTACAGTA
CAATGCACACATGGAATTAAGCCAGTAGTATCGACTCAACTACTGTTAAATGGCAGTCTAGCAGAAGAAG
ATGTGGTAATTAAATCTGCCAATTTCTCGGACAATGCTAAAACCATAATAGTACAGCTGAATGAATCTGT
AATAATTAATTGTACAAGACCCAACAACAATACAAGAAAGGGTATACATATGGGACCAGGGAAAACATTT
TATGCAACAGGAGCCATAATAGGAGATATAAGACAAGCACATTGCAATGTTAGTAGAACAGACCGGAATA
ACACTTTAAAAAGGGTAGCTAAAAAACTACAAGAACAATTTAATAACAACAAAGTTGTCTTTAAACAATC
CTCAGHAGGGGACCCAGAAATTGTAATGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGTAATACA
TCAGGGCTGTTTAATAGTACTTGGCCTTGGAATGATACTAAAGAGGCAAATAACACTAACACAATCACAC
TCCCATGCAAAATAAAACAAATCATAAACATGTGGCAGGCAGTAGGGAAAGCAATGTATGTCCCTCCCAT
TAGTGGGATAATTAAATGTGAATCTAATATTACAGGGCTGCTACTAACAAGAGATGGTGGTAGTAAGAAC
ACAACAGATAGTAATGACACAAACATAACACAAGAGGTCTTCAGACCAGGAGGAGGAGATATGAGGGACA
ATTGGAGAAGTGAATTATATAAATATAAAGTAGTAAGAATTGAACCATTAGGAGTAGCACCCACTAAGGC
AAAAAGAAGAGTGGTGGCAGAGAGAAAAAGAGCAGTGGGAATAGGAGCTGTGTTCCTTGGGTTCTTGGGA
GCAGCAGGAAGCACT
<U-257c1;PRT/1;HIV-1>
SATEQLWVTVYYGVPVWKEATTTLFCASDAKAYNTEVHNVWATHACVPTDPNPQEVMLNVTENFNMWKND
MVEQMQEDIISLWDQSLKPCVKLTPLCVTLSYTDANSTDVNHTKNSSEGMMEGEKMKNCSFNITTSMGNK
MQKEYALFHRLDVIPMDNESASANYSNYRLISCNTSVTTQACPKISFEPIPIHYCTPAGFAILKCNDKKF
SGKGGCRNVSTVQCTHGIKPVVSTQLLLNGSLAEEDVVIKSANFSDNAKTIIVQLNESVIINCTRPNNNT
RKGIHMGPGKTFYATGAIIGDIRQAHCNVSRTDRNNTLKRVAKKLQEQFNTTKVVFKQSSGGDPEIVMHS
FNCGGEFFYCNTSGLFNSTWPWNDTKEANNTNTITLPCKIKQIINMWQAVGKAMYAPPISGIIKCESNIT
GLLLTRDGGSKNTTDSNDTNITQEVFRPGGGDMRDNWRSELYKYKVVKRIEPLGVAPTKAKRRVVQREKR
<U-267_2c10;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGCGAAGGAGATCAAGAGGAATTGTCAGCACTCGTGGAGATG
GGGCATCATGCTCCTTGGGATGTTAATGATCTATAGTACTGCAGAAAAAACGTGGGTCACAGTATATTAT
GGGGTACCTGTGTGGAAGGAAGCAAACACCACTCTATTTTGTGCATCAGATGCTAAAGCATATGATACAG
AGGCACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAATAAAGTTGGA
AAATGTGACAGAGAACTTTAACATGTGAAAAAACAACATGGTAGAACAGATGCATGAGGATATTATCAGT
TTATGGGATCAAAGCCTACAGCCAAGTGTAAAATTAACCCCACTTTGTGTTACTTTAAATTGCTCTACTG
CGAATTTTACTAAAAGGGAATTTTACTAATAGCACTGAGCATGAAAAGCCGAGTGCAGAAATGAGAACTG
CTCTTTCAATATCACCACAATCGTAAGAGATAAGGTAACAAAAGAACTGCACTTTTTTTATAGAGATGAT
GTAGTACCAATAGATAATGCTAGTAATAATACCAGTTAGGTTAATAAATTGTAATACCTCTCAGTCATTA
CACAGGCCTGTCCAAAAGATATCCTTTGAGCCAATTCCTATACATTATTGTGCCCGGCTGGTTTTGCGAT
TCTAAAGTGTAATGATAAGACATTTAATGGAACAGGGCTATGTAAAAATGTCAGCACAGTACAATGTACA
CATGGAATTAGACCAGTAGTGTCAACTCAACTGTTGTTAAATGGGAGTCTAGCAAGAAAAAAGGTAGTAG
TTAGATCTGAGGAGTTTTCAGACAAATGCTAAATCCATAATAGTACAGCGAATACATCTGTAGTAATTAA
TTGTACAAGACCCGGCAATAATACAAGAAGAAGCATACCTATGGGACCAGGAAGAGTAGTTTATGCAACA
GATATAATAGGAGACATAAGACAGGCACATTGTAACCTTAGTAGAGCAGCATGGAATAACACTTTAAAGC
TGATAGCCGCAGAATTAAAAGAAATATATAATAAAACAATAGCCTTTAATCGATCCTCAGGAGGGGACCC
AGAAATTGTAATGCACACTTTTAATTGTGGGGGGGAATTTTTCTACTGTAATACAACACAACTGTTTAAT
AGTGCTTGGAACAGTACTAATATTTATACTGGGAATAATTCTACTAATGACACCATCTCTAATGACGCCA
TCTCACTCCCATGTAGAATAAAACAAATTGTAAACATGTGGCAGGAAGTAGGAAAAGCAATGTATGCCCC
TCCCATCAGAGGAAACATCAGCTGTTCCTCAAATATTACAGGGCTGATATTGACAAGAGATGGCGGGAAT
AGTAGTAGTAATACCGATCTTCAGACCTCAGGAGAGGGAATATAAAAGGACAATTGGAGAAGTGAATTAT
ATAAATATAAAGTAGTAAGAATTGAACCATTAGGATTAGCACCCACCAAGGCAAAGAGGAGAGTGGTGCG
GSGAGAAAAAGAGCGGTAACGTTCGGAGCTTTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-267_2c10;PRT/1;HIV-1>
STAEKTWVTVYYGVPVWKEANTTLFCASDAKAYDTEAHNVWATHACVPTDPNPQEIKLENVTENFNMWKN
NMVEQMHEDIISLWDQSLQPSVKLTPLCTLNCSTANFTKRNFSTNSTEHEKPSAEMRNCSFNITTIVRDK
VTKEHALFYRDDVVPIDNASNNTSYRLINCNSVITQACPKISFEPIIPIHYCAPAGFAILKCNDKTFNGT
GLCKNVSTVQCTHGIRPVVSTQLLLNGSLAEKKVCVRSEEFSDNAKSIIVQLNTSVVLNCTRPGNNTRRS
IPMGPGRVFYATDIGDIRQAHCNLSRAAWNNTLKLIAAELKEIYNKTIIAFNRSSGGDPEIVMHTFNCGG
EFFYCNTTQLFNSAWNSTNIYTGNNSTNDTISNDAISLPCRIKQIVNMWQEVGKAMYAPPIRGNISCSSN
ITGLILTRDGGNSSSNTEIFRPQGGNIKDNWRSELYKYKVVRIEPLGLAPTKAKRRVVRREKE
<U-300_3c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAAAGTGAAGGGGATCAGGAAGAATTATCAGTGCTTGTGGGGATG
GGGCACCATGCTCCTCGGGATATTGATGATCTGTAGTGCTGCAGAAAATTTGTGGGTCACAGTCTACTAT
GGGGTACCTGTGTGGAAAGAAGCAACCACCACTCTATTTCGTGCATCAGATGCTAAAGCATATGATACAG
AGGTACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTAGTATTGGA
AAATGTTACAGAAAATTTTAATATGTGGAAAAATGACATGGTAGAACAGATGCAGGAGGATATAGTCAGT
TTATGGGATCAAGCCTAAAGCCATGTGTGAAAATCAACTCCACTCTGTGTTACTCTAAATTGTACTGATG
TGAAGAAGAATGCTAATAATACCACTGGTAATACCACTGATGGTAACGTGGAAAGGTTGGAGAAAGAAGA
AATAAAAAACTGCTCTTTCAATATCACCACAAGCATAAGAGATAAGATGCGGAAAGAATATGCACTTTTT
TATAGCCTTGATGTAGTACCAATAGATAAGGATAATACAAGCTATAGGTTGATAAGTTGTAACACCTCAG
TCATTACACAGGCCTGTCCAAAAGTATCCTTTGAGCCAATTCCCATACATTATTGTGCCCCGGCTGGTTT
TGCGCTTCTAAAATGTAATGATAAGGAGTTCAATGGAACAGGACCATGTAGGAATGTCAGCACAGTCCAA
TGTACACATGGAATTAGGCCAGTAGTATCAACTCAACTGCTGTTAAATGGCAGTCTAGCAGAAGAAAAGA
TAGTAATTAGATCTGAGAATTTCACGAGCAATGCTAAAACTATAATAGTACAGCTGAATAAATCTATAGA
AATTAATTGTATAAGACCCAACAACACAAGAAGAAGTATACATATAATGGACCAGGGGGGGAGCATTTAT
GCAACAGAAATAATAGGAGATATAAGACAAGCACATTGTACCCTCAATAGAACAGAATGGAATAACACTC
TAGGACAGATAGTTAAAAAATTAAGAGAACAATATGGGAATAAAACAATAAAATTTACGCAGCCCTCCTC
AGGAGGGGACCCAGAAGTTGTAATGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGTAATTCATCA
CAGCTGTTTAATAGTACTTGGGATGTTACTGAAGGGTCAAATAACACTGAAGGAAGCAACGATACAGGAA
TCATACTCCCGTGCAGAATAAAACAAATAATAAACATGTGGCAGAAAGTAGGAAAAGCAATGTATGCCCC
TCCCATCAGAGGACAAATTAACTGTACATCAAATATTACAGGGCTACTATTAATAAGAGATGGTGGTAAC
AACGGGACCGACAACGGGACCGAGACCTTCAGACCTGGAGGAGGAGATATGAGGGGACAATTGGAGAGTG
AATTATATAAATATAAAGTAGTAAAAATTGAACCATTAGGAGTAGCACCCACCAAGGCAAAGAGAAGAGT
GGTGCAGAGAGAAAAAAGAGCAGTGGGAATAGGAGCTTTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGC
ACT
<U-300_3c1;PRT/1;HIV-1>
SAAENLWVTVTTGVPVWKEATTLFRASDAKAYDTEVHNVWATHACVPTDPSNPQEVVLENVTENFNMWKN
DMVEQMQEDIVSLWDQSLKPCVESTPLCVTLNCTDVKKNANNTTGNTTDGNVERLEKEEIDNCSFNITTS
IRDKMRKEYALFYSLDVVPIDKDNTSYRLISCNTSVITQACPKVSFEPIPIHYCAPAGFALLKCNDKEFN
GTGPCRNVSTVQCTHGIRPVVSTQILLNGSLAEEKIVIRSENFTSNAKTIIVQLNKSIEINCIRPNNNTR
RSIHIGPGGAFYATEIIGDIRQAHCTLNRTEWNNTLGQIVKKLREQYGNKTIKFTQPSSGGDPEVVMHSF
NCGGEFFYCNSSQLFNSTWDVTEGSNNTEGSNDTGIILPCRIKQIINMWQKVGKAMYAPPIRGQINCTSN
ITGLLLIRDGGNNGTDNGTETFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKAKRRVVQREKR
<U-302c17;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGGATCAGGAGGAATTATCAGTGCTTGTGGACATG
GGGCACGATGCTCCTTGGGATGTTGATGATCTGTAGTGCTGTAGAACAATTGTGGGTCACAGTCTATTAT
GGGGTGCCTGTGTGGGAAGAAGCGACCACCACTCTATTTTGTGCATCAGATGCTAAAACATATGATCCAG
AGGTACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTAGTATTGGG
AAATGTGACAGAAAACTTTAACATGTGGAAAAATGACATGGTAAACCAAATGCATGAGGATATAATCAGT
TTATGGGATCAAAGTTTAAAGCCATGTGCAAAATTAACCCCACTCTGTGTTACTCTAATTGCAACTGATA
AGTTGAATATTAATACTACCAGTACCAATAGTAGTACCAATAATACTACTAGTAGTGGAGTGGATGAAGG
GGGAATGAAAAACTGCTCTTTCAATGTCACCACAAGCATAAGAGATAGGGTGCAGAAAGAATATGCACTT
TTTTATAAACCTGATGTAGTACCAATAGATGATAATACTAATAATACTAGCTATAGGTTGATAAATTGTA
ACACCTCAGTCATTACACAAGCCTGTCCAAAGGTAACCTTTGATCCAATTCCCATACATTATTGTGCCCC
GGCTGGTTTTGCGATTCTAAAATGTAACAATAAGACGTTCAATGGATCAGGACCATGTACAAATGTCAGC
ACAGTACAATGTACACATGGAATTAAACCAGTGGTGTCGACTCAATTGCTGTTAAATGGCAGTCTAGCAG
AGGAAGAAATAGTAATCAGGTCTGAAGATTTCACGGACAATGATAGAACCATAATAGTACAGCTGAATGA
ATCTGTAGTAATTCATTGTACAAGACCCAACAACAATACAAGAAAAAGTATACACCTAGGACCAGGGAGT
GCATTTTATGCAACAGGAGATATAATAGGAGATATAAAACAAGCACATTGTAACATTAGTAGAGCAAATT
GGACTAACACCTTAAAACAGATAGCTGGAAAATTAAAAGAACAGTTTGGAAATAAGACAATATTCTTTAA
TCAATCCTCAGGAGGGGATCCAGAAATTGTAACACACAGTTTCAATTGTAGAGGGGAATTTTTCTACTGT
AATACATCACAATTGTTTAACAGTACTTGGCTTCATAATAATAGTACTGGGAATGATACTGAAAAGAATG
GTAATATCACACTCCCACGCAGAATAAAACAAATTATAAACATGTGGCAGCAAGTAGGAAAAGCAATGTA
TGCCCCCCCTGTCAAAGGACTAATTACATGTTCATCAAATATTACAGGACTGCTATTAGTAAGAGATGGT
GGTAACAACACCAACGCCACCGACACCGAGACCTTCAGACCTGGAGGAGGAGATATGAGGGACAATTGGA
GAAGTGAATTATATAAATATAAAGTAGTAAAAATCAAACCATTAGGAATAGCACCCACCAAGGCAAAAAG
AAGAGTGGTGCAGAGAGAAAAAAGAGCAGCACTAGGAGCTATGTTCCTTGGGTTCTTGGGAGCAGCAGGA
AGCACT
<U-302c17;PRT/1;HIV-1>
SAVEQLWVTVYYGVPVWEEATTTLFCASDAKTYDPEVHNVWATHACVPTDPNPQEVVLGNVTENFNMWKN
DMVNQMHEDIISLWDQSLKPCAKLTPLCVTLNCTDKLNINTTSTNSSTNNTTSSGVDEGGMKNCSFNVTT
SIRDRVQKEYALFYKPDVVPIDKNTNNTSYRLINCNTSVTTQACPKVTFDPIPIHYCAPAGFAILKCNNK
TFNGSGPCTNVSTVQCTHGIKPVVSTQLLLNGSLAEEEIVIRSEDFTDNDRTIIVQLNESVVIHCTRPNN
NTRKSIHLGPGSAFYATGDIIGDIKQAHCNISRANWTNTLKQIAGKLKEQFGNKTIFFNQSSGGDPEIVT
HSFNCRGEFFYCNTSQLFNSTWLHNNSTGNDTEKNGNITLPRRIKQIINMWQQVGKAMYAPPVKGLITCS
SNITGLLLVRDGGNNTNATDTETFRPGGGDMRDNWRSELYKYKVVKIKPLGIAPTKAKRRVVQREKR
<U-305c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAGGGGGACCAGGAAGAATTATCAGCACTTGTGGAGATG
GGGCATCATGCTCCTTGGGATGTCAATGATCTGTAATGCTACAAAAGATTTGTGGGTCACAGTTTATTAT
GGGGTACCTGTATGGAAAGAAGCAAACACCAGTCTATTTTGTGCATCAGATGCTAAAGCATATGATACAG
AGGTACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTATTCATGAA
CAATGTGACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGAACAAATGCATGAGGATATAATCAGT
TTATGGGATCAAAGCCTAAAACCATGTGTAAAATTAACCCCACTCGGTGTTACTCTAGATTGCACTAAGG
CTAATATTACCAATAATAGTACCACTAATAGTAGCGGGGGAATAGAGGAGGGAAGAGACATAGAAAATTG
CTCTTTCAATATCACCACAAACATAAGAGATAAGATAAAGAAAGAATATGCACTTTTTTATAGCCTTGAT
GTGATAGCAATAGATGATAGTAGTAATAGTAGTAATAGAAGCTATAGGTTGAGAGGTTGTAACACCTCAA
CCATCACACAGGCCTGTCCAAAGGTAACCTTTGAGCCAATTCCAATACATTATTGTGCCCCAGCTGGTTT
TGCGATTCTAAAGTGTAACGATAAGAAGTTCAATGGAACAGGACCATGTAAAAATGTCAGTACAGTACAA
TGTACACATGGAATTAGGCCAGTAGTATCAACTCAACTGCTGCTAAATGGCAGTATAGCAGAAAAAGAGG
TAGTAATTAGGTCCGCTAATTTCACGGACAATGCTAAAACCATAATAGTACAGCTGAATAACTCTGTACA
AATTAATTGCACAAGACCCGGCAACAATACAAGAAAAAGTATACATATAGGACCAGGCAGAGCATTTTAT
GCACATGAAATAATAGGGGAGATAAGACAAGCACATTGTACCCTTAACAGAACACAATGGAATAACACTT
TAAAACAGATAGTTATAAAATTAAGAGAACAATTTAACAATAAGACAATAGTCTTTAATCACTCCTCAGG
AGGGGACCCAGAAATTGTAACACACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGTAATACATCACAA
TTATTTAATAGTACCTGGAGGAGTAATGAAACTGTAAATGACACTATGGGAAAGGACACAAATGACACAA
CAATCACACTCCCATGCAGAATAAAACAAATTATAAACATGTGGCAGGAAGTAGGAAAAGCAATGTATGC
CCCGCCCATCAGAGGACAAATTAGCTGTTCATCAAATATTACAGGGCTGCTATTAACAAGAGATGGTGGT
GTGAACGAGACCAACGCCACCGAGGTCTTCAGACCTGGAGGAGGAGATATGAGGGACAATTGGAGAAGTG
AATTATATAAATATAAAGTAGTAGAAATTGAACCATTAGGAATAGCACCCACCAAGGCAAAGAGAAGAGT
GGTGCAGAGAGAGAAAAGAGCAGTGGGAATAGGAGCTGTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGC
ACT
<U-305c1;PRT/1;HIV-1>
NATKDLWVTVYYGVPVWKEANTSLFCASDAKAYDTEVHNVWATHACVPTDPNPQEVFMNNVTENFNMWKN
NMVEQMHEDIISLWDQSLKPCVKLTPLGVTLDCTKANITNNSTTNSSGGIEEGRDIENCSFNITTNIRDK
IKKEYALFYSLDVIAIDDSSNSSNRSYRLRGCNTSTITQACPKVTFEPIPIHYCAPAGFAILKCNDKKFN
GTGPCKNVSTVQCTHGIRPVVSTQLLLNGSIAEKEVVIRSANFTDNAKTIIVQLNNSVQINCTRPGNNTR
KSIHIGPGRAFYAHEIIGEIRQAHCTLNRTQWNNTLKQIVIKLREQFNNKTIVFNHSSGGDPEIVTHSFN
CGGEFFYCNTSQLFNSTWRSNETVNDTMGKDTNDTTITLPCRIKQIINMWQEVGKAMYAPPIRGQISCSS
NITGLLLTRDGGVNETNATEVFRPGGGDMRDNWRSELYKYKVVEIERLGIAPTKAKRRVVQREKR
<U-323c11;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGCGAAGGGGATCAGGAAGAATTGGCAGCACTTGTGGAGATG
GGGCACCATGCTCCCATGGGGCACCATGCTCCTTGGGATGTTAATGATGATCTGTAGTGCTGCAGAAGAA
AAATGGGTCACAGTCTATTATGGGGTACCTGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATCAG
ATGCTAAAGCATATGACACAGAGGTACATAATGTTGGGCCACAACATGCCTGTGTACCCACAGACCCTAA
CCCACAAGAAGTAGTATTGGGGAAATGTGACAGAAAATTTTAATGTGTGGAAAAATGACAGGTAGAACAG
ATGCATGAAGATATAATCAGCTTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCACTCTGTG
TTGCTTTAAATTGCACTAATGTGAATGATACTAGGACAAACAATAGTAGTAGTAGTGATAAAAATGATGC
TAAAACCAATAGTAGTAGTAGTTGGGAAAGGATGGAAGGAGAAGTAAAAAACTGCTCTTTCAATGTTACC
ACAAGAATAAGAAACAAGGTGCAGAAAGAATATGCACTTTTTTATAAGCTTGATGTAGTGCCAATAGAGA
AGGATAATGCAAGCTATACATTGATAAATTGTAACACCTCAGTCATTACACAGGCCTGTCCAAAGGTATC
TTTTGAACCAATTCCCATACATTATTGTGCCCCGGCTGGTTTTGCGATTCTAAAGCGTAATGATAAGAAG
TTCAATGGAAAAAGCCCATGTACAAATGTCAGCACAGTACGATGTACACATGGAATTAGGCCAGTAGTGT
CAACTCAACTACTGTTAAATGGCAGTCTAGCAGAAGAAGGGGTAGTAATTAGAGATCTGAAAATCACGAA
CAATGTTAAAACCATAATAGTACAGCTGAACAAATCTGTAAAAATTAATTGTACAAGACCCAACAACAAT
ACAAGAAAAAGTATAAATATAGGACCAGGGGAGCATTTTATGCAACCAGGAGCAATAATAGGAAATATGA
GACAAGCACATTGTAACCTTAATGGAACAGAATGGAAGAACACTTTAAGACAGGTAGTTATAAGCTTAAG
AGAGAAATTTGGGAAGAAGACAATAGTCTTCAACCAATCCTCAGGAGGGGATTTAGAAATTATAATGCAC
AATTTTAATTGTGGAGGGGAATTTTTCTACTGTGATACAACACAGCTGTTTAATAGTACTTGGCTGCCTA
ATGAGACTACAGAGTCAAATAACATTACTGGAGGACCTAATGACACACTCACGCTCCCATGTAGAATAAA
ACAAATTATAAACAGATGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATCAGTGGGCAAATTAGA
TGCTCATCAAATATTACGGGGCTGCTATTAACAAGAGATGGTGGTGAGGAGCAGAATGACACTGAGGTCT
TTAGACCTGGAGGAGGAGATATGAGGGACAATTGGAGAAGTGAATTATATAAATATAAAGTAGTAAGAAT
TGAGCCATCAGGAGTAGCACCCACCAAGGCAAAGAGAAGAGTGGTGCAAAGAGACAAAAGAGCAGTGGGA
GCACTAGGAGCTATGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-323c11;PRT/1;HIV-1>
SAAEEKWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHACVPTDPNPQEVVLGNVTENFNVWKN
DMVEQMHEDIISLWDQSLKPCVKLTPLCVALMCTNVNDTRTNNSSSSDKNDAKTNSSSSWERMEGEVKNC
SFNVTTRIRNKVQKEYALFYKLDVVPIEKDNASYTLINCNTSVITQACPKVSFEPIPIHYCAPAGFAILK
RNDKKFNGKGPCTNVSTVRCTHGIRPVVSTQLLLNGSLAEEGVVIRSENLTNNVKTIIVQLNKSVKINCT
RPNNNTTKSINIGPGRAFYATGAIIGNMRQAHCNLNGTEWKNTLRQVVISLREKFGKKTIVFNQSSGGDL
EIIMHNFNCGGEFFYCDTTQLFNSTWLPNETTESNITGGPNDTLRTLPCRIKQIINRWQEVGKAMYAPPI
SGQIRCSSNITGLLLTRDGGEEQNDTEVFRPGGGDMRDNWRSELYKYKVVRIEPSGVAPTKAKRRVVQRD
<U-334c3;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAAAGTGAAGGGGACCAGGAAGAATTATCAGCACTTATGGAGATG
GGGCACCATGCTCCTATGGAGATGGGGCACCATGCTCCTTGGGCTATTAATGATCTGTAATGCTATAGAA
GAATCGTGGGTCACAGTCCATTATGGAGTACCTGTGTGGAAAGAAGCAAACACCACTCTGTTTTGTGCAT
CAGATGCTAAAGCATATGATACAGAGGTACATAATGTTTGGGCCACACATGCCTGTGTACCCACAAACCC
CAACCCACAAGAAGTAGACTTGGGAAATGTGACAGAAAATTTTAATGCATGGAAAAATGACATGGTAGAA
CAAATGCATGAGGATATAATTAGTTTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACTCCACTCT
GTGTTACTCTACAGTGCACTGATTTGAGGAATGATACTAATACCACTAGTAGTCCTAATACCACTAGTGG
TAACTGGATGGATAAAAGGGAAATGAAAAACTGCTCTTTCAATATCACCACAAGCATAAGAGATAAGCTG
CAGAAAACATTTGCACTTTTTTATAAACTTGATATAGTACCAATAAATGAGGACAAAAACAGTAGTAATA
TTGATAATACCAGTTATAGGTTGATAAGTTGTAATACCTCAGTCATTACACAGGCCTGTCCAAAGGTATC
CTTTGAGCCCAATTCCCATACATTATTGCCCCGGCTGGTTTTGCGATTCTAAAAATGTAAAGATGAGGAG
TTCAATGGAACAGGACCATGTAAAAATGTCAGTACAGTACAATATACACATGGAATTAGGCCAGTAGTAT
CAACTCAACTGGCTGTTAAATGGCAGTCTAGCAGAACAAGGGGTAGTACTTAGATCTAAAATATCTCAGA
CAATACTAAAACCATAATAGTACAGCTAAAAGAAGCTGTAACAATTAAGTGTACAAGACCCAACAACAAT
ACAAGAAAAAGTAGACATATAGGACCTGGGAGAGCATTTTATGCAACAGGAGACATAATAGGAGATATAA
GACAAGCCCATTGTAACATCAGTGCAACAAAGTGGAATGACACGTTACGTCAGATAGTTGAAAAATTACA
AGGATCATTTAAGAATAAAACAATAAGCTTCAAGCGATCCTCAGGAGGGGATCCAGAGATTGTAATGCAC
AGTTTTAATTGTGGAGGGGGAATTTTTCTATTGTAATTCACAAAACTGTTTAATAGTACTTGGTATAGTA
ATGGGACTAGTACTTTTGATAATACTACTGAACGAACAAATGACACTATCATACTCCCATGCAGAATAAA
ACAAATTATAAACATGTGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATCCCAGGACTAATTAAC
TGTTCATCAAATATTACAGGACTGCTATTAATAAGAGATGGTGGTAATAACTATACTGACAATACTGAGA
TCTTCAGACCTGGAGGAGGAGACATGAGGGACAATTGGAGAAGTGAATTATATAAATATAAAGTAGTAAA
AGTTGAACCATTAGGTATAGCACCCACCAAGGCAAAGAGAAGAGTTGGTACAGAGAGAAAAAGAGCAGTG
GGAATAGGAGCGTTTTTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-334c3;PRT/1;HIV-1>
NAIEESWVTVHYGVPVWKEANTTLFCASDAKAYDYEVHNVWATHACVPTNPNPQEVDLGNVTENFNAWKN
DMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTDLRNDTNTTSSPNTTSGNWMDKREMKNCSFNITTSI
RDKLQKTFALFYKLDIVPINEDKNSSNIKNTSYRLISCNTSVITQACPKVSFEPIPIHYCAPAGFAILKC
KDEEFNGTGPCKNVSTVQYTHGIRPVVSTQLLLNGSLAEQGVVLRSKNISDNTKTIIVQLKEAVTIKCTR
PNNNTRKSIHIGPGRAFYATGDIIGDIRQAHCNISATKWNDTLRQIVEKLQGSFKNKTISFKRSSGGDPE
IVMHSFNCGGEFFYCNSTKLFNSTWYSNGTSTFDNTTERTNDTIILPCRIKQIINMWQEVGKAMYAPPIP
GLINCSSNITGLLLIRDGGNNYTDNTEIFRPGGGDMRDNWRSELYKYKVVKVEPLGIAPTKAKRRVVQRE
<U-349c2;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGAGATCAGGAAGAATTGTCAGCGCTTGTGGACATG
GGGCACCATGCTCCTTGGGATGTTGATGATCTGTAGTACTGCAGAACAACTGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGGAAAGAAGCAACTACCACTTTATTTTGTGCATCAGATGCTAAAGCAYSYGAVACAG
AAGCACATAATGTTTGGGCCACACATGCCTGTGTACCCACGGACCCTAACCCACAAGAAGTAGTAAATAA
TGTGACAGAAAATTTTAACATGTGGAAAAATGACATGGTAGAACAGATGCATGAGGACATAATCAGTGTA
TGGGACCAGAGTCTAAAGCCATGTGTAAAATTAACCCCACTCTGTGTTACTTTAAATTGCACTAATTGGA
ATGGTACTAATACCAATAATGCTAATACTACCAGTAGTCCTAATATTACCAGTACTACTACTGCCAATAT
TTATGAGAAAAGAATGGAAGAAGGAGAAATACAAAATGCACTTTTCAATGTCACCACAAGCATAAGGGAT
AAGGTAAAAGAAGAATATGCACTTTTTTATAGATCTGATGTAGGCCAAATAGGTAATAATAGTAATAATA
CATATACATTGATAAATTGTAATTCCTCAGTCATTACACAGGCTCGTCCAAAGATATCCTTTGAACCAAT
TCCCATACATTATTGTACCCCGGCTGGTTTTGCGATTCTAAAATGCAATAATAAGACCTTCAATGGAACA
GGACCATGTAACAATGTCAGCACAGTACAGTGTACACATGGTATTAGGCCAGTAGTATCAACTCAATTGT
TGTTAAATGGCAGTCTAGCAGAAGATGAGATAATGATTAGATCTGCAATCTCTCGGACAATACTAAAAAA
CATAATAGTACAGCTGAATAAATCTGTAGAAATTAATTGTACAAGACCCAACAATAATACAAGAAAAAGT
ATAAATAAGGACCAGGGAGAGCATTTTATGCAACAAGGAGATATAATAGGAAACATAAGACATGCATATT
GTACCATTAATGAAACAAAATGGAATGAAACTTTAAGACAGATAGCTACAAAATTACACAAACAATTTAA
TAAAACAATAATCTTTGAGCAGTCCTCAGGAGGAGACCCAGAAATTACAACGCACAGTTTTAATTGTGGA
GGGGAATTTTTCTACTGTAATACAACACCGCTGTTTAATAGCACTTGGGTTAAGACTCAGAATGATACTA
TAGGGTCTAAGACTCAGAATGCTACTACAGGGTTAAATGGCACTATCATACTCCCATGCAGAATAAAACA
AATCATAACAGATGGCAGGAAGTAGGAAGAGCAATGTATGCCCCCTCCCATCAAAGGAATAATTAGATGT
TCATCAAATATTACAGGGCTGATATTGACAAGAGATGGTGGTGGTAATGAGAGCAGGGAAAATGAGACCT
TCAGACCTGGAGGAGGAGATATGAGGGACAATTGGAGAAGTGAATTATATAAATATAAAGTAGTAAAAAT
TGAGCCAATAGGACTGGCACCCACCAAGGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCGGTAACG
CTGGGAGCTATGTTCCCTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-349c2;PRT/1;HIV-1>
STAEQLWVTVYYGVPVWKEATTTLFCASDAKAYDTEAHNVWATHACVPIDPNPQEVVLNVTENFNMWKND
MVEQMHEDIISVWDQSLKPCVKLTPCVKLTPLCVTLNCTNWNGTNTNNANTTSTTTANIYEKRMEEGEIQ
NCTFNVTTSIRDKVKEEYALFYRSDVGQIGNNSNNTYTLINCNSSVITQARPKISFEPIPIHYCTPAGFA
ILKCNNKTFNGTGPCNNVSTVQCTHGIRPVVSTQLLLNGSLAEDEIMIRSANLSDNTKNIIVQLNKSVEI
NCTRPNNNTRKSINIGPGRAFYATGDIIGNIRHAYCTINETKWNETLRQIATKLHKQFNKTIIFEQSSGG
DPEITTHSFNCGGEFFYCNTTPLFNSTWVKTQNDTIGSKTQNATTGLNGTIILPCRIKQIINRWQEVGRA
MYAPPIKGIIRCSSNITGLILTRDGGGNESRENETFRPGGGDMRDNWRSELYKYKVVKIEPIGIAPTKAK
RRVVQREKR
<U-350c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGGATCAGGAAGAATTATCAGCACTTGTGGACATG
GAGCAACATGCTCACGATGCTCCTTGGGATGTTAATGATCTGTAGTGCTGCAGATCAATTGTGGGTCACA
GTCTATTATGGGGTACCTGTGTGGAAAGAAACAACCACCACTCTATTTTGTGCATCAGATGCTAAAGCAT
ATGATAAAGAGGTACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGT
AATATTGGAAAATGTGACAGAAAAATTTTAACGCGTGGAAAATGACATGGTAGAACAGATGCATGAGGAT
ATAATTAGTTTATGGGATCAAAGCTTAAAGCCATGTGTAAAATTAACCCCACTCTGTGTTACTTTAAATT
GCACTGATGCTATATTACTAATACCAATGATAATAGAGCCCAATAGTAGTGTGGTGAAACTGATAGAGAA
AGGAGAAATAAAAAACTGCTCTTTCAATATCACCACAAGCATAAGAGATAAGATGCAGAAAGCATATGCA
CTTTTTTATAAACTTGATGTAGAACCAATAGAGAATAATACTACTAGCTATAGGTTGATAAGTTGTAACA
CCTCAGTCATTACACAAGCCTGTCCAAAGGTATCCTTTGAGCCAATTCCCATACATTTTTGTGCCCCGGC
TGGTTTGCGATTCTAAAGTGTAACAATAAGACATTCGAGGGAAAAGGACCATGTAAAAAATATCAGCACA
GTACAATGTACACATGGAATTAGGCCAGTAGTATCAACTCAATTGCTCTTAAATGGCAGTCTGGCAGAAG
AAGAGATAGTGATTAGATCTGCAATTTTTTCAAACAGTGCTAAAACCATAATAGTACAGTTGAATGCATC
TGTAGAAATTATCGTACAAGACCCAACAACAATACGAGAAAAAGGTATAGTTATAGGACCAGGGAGAAAA
GTTATTGCAACAGAAAAAATAATAGGAGATGTAAGACAAGCACATTGTAACATTAGTATAACAAAATGGA
ATAATACTTTAGGCCATATAGTTAATAAATTAAGAAAACAATTTGGGGAAAATAAAACAATAGTCTTTAA
GCAACACTCAGGAGGGGATCCAGAAGTTATAATGCATAATTTTAATTGTGCAGGGGAATTTTTCTACTGT
AATACAACAGGACTGTTTAATAGCACTTGGCATTGGAATGGTACTTGGAGTGGTACTGAAAGGAGAAATA
GCACTGAAGGAAATGACACACTTACACTCCCATGCAGAATAAAACAAATTATAAACATGTGGCAGGAAGT
AGGAAAAGCAATGTATGCCCTCCCGTTAACGGACAGATTAGATGTTTATCAAAATATTACAGGACTGCTA
TTAACAAGAGATGGTGGTAATAACAATAACACAAACGACACCGAAACCTTCAGACCTGAAGGAGGAGATA
TGAGGGACAATTGGAGAAGTGAATTATATAAATATAAAGTAGTAAGAATTGAACCATTAGGAGTAGCACC
CACCAAGGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCACTGGGAGTAGGAGCAGCTTTGTTCCTT
GGGTTCTTGGGAGCAGCAGGAAGCACT
<U-350c1;PRT/1;HIV-1>
SAADQLWVTVYYGVPVWKETTTTLFCASDAKAYDKEVHNVWATHACVPTDPNPQEVILENVTENFNAWKN
DMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCTDANITNTNDNEPNSSVVKLIEKGEIKNCSFNITTSI
RDKMQKAYALFYKLDVEPIENNTTSYRLISCNTSVITQACPKVSFEPIPIHFCAPAGFAILKCNNKTFEG
KGPCKNISTVQCTHGIRPVVSTQLLLNGSLAEEEIVIRSDNFSNSAKTIVVQLNASVEINRTRPNNNTRK
GIVIGPGRKVIATEKIIGDVEQAAHCNISITKWNTLGHIVNKLRKQFGENKTIVFKQHSGGDPEVIMHNF
NCAGEFFYCNTTGLFNSTWHWNGTWSGTERRNSTEGNDTLTLPCRIKQIINMWQEVGKAMYAPPVNGQIR
CLSNITGLLLTRDGGNNNNTNDTETFRPEGGDMRDNWRSELYKYKVVRIEPLGVAPTKAKRRVVQREKR
<U-386_2c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGAATGAGAGTGAAGGGGATCAGGAAGAATTATCAGCACTTGTGGATATGG
GGCATCTTGCTCCCTGGGATGTTGATGATCTGTAGTGCTGCAGACAAGTTGTGGGTCACAGTCTATTATG
GGGTACCTGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATCAGATGCTAAAGCATATAGTGCAGA
GGTACATAATGTCTGGGCCACACATGCCTGTGTACCCACAGACCCCGACCCACAGGAAATAGTATTGGAA
AATGTAACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCAGGAGGATATAATCAGTT
TATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCTCTCTGTGTCACTTTAAACCGCACTGATGA
ATTGCGGACTACTAATAAGACTACTAATAAGACCAATGATACAGAGACGAATACTACTAATACCACCAGC
TGGGAAAAAGGGGAAATGAAAAACTGCTCTTTTGATGTCACCACAAACATAAGAGATAAGTGGCAGAGAG
AATATGCACTTTTTTATAAGCTTGATGTAGTACCAATAGATAATGATGGTAATGGTAATAGTAGTAATAA
TGCCACTGATAATAATAATACTACCAATAATACCAACTATAGGTTGATAAGTTGTAACACCTCAGTTATT
ACACAGGCCTGTCCAAAGGTATCTTTGAGCCAATTCCCATACATTATTGTGCCCCAGCTGGTTTTTGCGA
TTCTAAAGTGTAAAGATGAGAAGTTCAGTGGAACAGGACCATGTAAAAATGTCAGCACAGTACAATGCAC
ACATGGAATTAGGCCAGTAGTATCAACTCAACTGCTGTTGAATGGCAGTCTAGCAAAAGAAGAGATAATA
ATTAGATCTGAAAATCTCACGAACAATGCTAAAACCATAATAGTACAGCTGAATGAATCTGTATCAATTA
ATTGTATAAGACCCAACAATAATACAAGAAGAGGTATACCTATAGGACCAGGGCAAGCATTTTATGCAAC
AGGGGATATAATAGGGGATATAAGAAAAGCACATTGTATAGTTAACAGTACACAATGGAATAACACTTTA
GCACAGGTAGCCATAAAATTAAATGAACACTTTCCAAATAAAACAATAGTCTTTAAGCAGTCCTCAGGAG
GGGACCCAGAAATTGTAATGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGTGATTCAACACCACT
GTTTAACAATACTTGGAATGAAACACATTTTAATAATACTTGGGATAGTATTGAAAAGGGAAAAATCATA
CTCCAATGCAGAATAAAACAAATTATAAATATGTGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCA
TCAGAGGGCTGATTAACTGTACATCAAACATTACAGGGCTACTATTAACAAGAGATGGTGGCAAGAAAGA
GAATGAGAGTGATACTATCGAGATCTTCAGACCTGGAGGAGGAGACATGAGGAACAATTGGAGAAGTGAA
TTATATAAATATAAAGTAGTAAAAAATTGAACCATTAGGAGTAGCACCCACCAAGGCAAAAGAAGAGTGG
TGCAGAGAGAAAAAAGAGCAGCGCTAGGAGCTTTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-386_2c1;PRT/1;HIV-1>
SAADKLWVTVYYGVPVWKEATTTLFCASDAKAYSAEVHNVWATHACVPTDPDPQEIVLENVTENFNMWKN
NMVEQMQEDIISLWDQSLKPCVKLTPLCVTLNRTDELRTTNKTTNTNDTETNTTNSTTSWEKGEMKNCSF
DVTTNIRDKWQREYALFYKLDVVPIDNDGNGNSSNNATDNNNTTKYTNYRLISCNTSVITQACPKVSFEP
IPIHYCAPAGFAILKCKDEKFSGTGPCKNVSTVQCTHGIRPVVSTQLLLNGSLAKEEIIIRSENLINNAK
TIIVQLSVSINCIRPNNNTRRGIPSIGPGQAFYATGDIIGDIRKAHCIVNSTQWNNNTLAQVAIKLNEHF
PNKTIVFKQSSGGDPEIVMHSFNCGGEFFYCDSTPLFNNTWNETHFNNTWDSIEKGKIILQCRIKQIINM
WQEVGKAMYAPPIRGLINCTSNITGLLLTRDGGKKENESDTIEIFRPGGGDMRNNWRSELYKYKVVKIEP
LGVAPTKAKRRVVQREKR
<U-031_2c10;DNA;HIV-1>
AGAAAGAGCAGAAGCAGTGGCAATGAGAAGTGAAGGAGATCATGAAGAACTATCAGAACTTATGGAGAGG
GGGCATGATGCTCCTTGGGATATTCATGATCTGTAGTGCTACAGAACAATTGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGGAAAGAAAGCAAATACCACTCTATTTTTGTGCATCAGATGCTAAAGCATAAGACAG
AGGTACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTATTATTGCC
AAATATGACAGAAGATTTTTAACATGTGGAAAAAAATAACATGGTAGAACAGATGCATGAGGATATCAGT
TTGTGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCACTCTGTGTTACTTTAAAATGCACTGACT
TGAATACTACTAATACTATCAATAGTAGTGACTTGATGGAGAAGGGAGAAATAAAGAACTGCTCTTTCAA
TATCACCAAACATAAGAGATAAGATGCAGAAAGACTATGCGCTTTTTTTTATAGACTTGATGTAGTACCA
ATAGATAATGATAATACTAGCTATAGGTTGATAAGTTGTAACACCTCAGTCATTACACAGGCCTGCCCAA
AGGTATCTTTTGAGCCAATTCCCATACATTGTTGTGCCCCGGCTGGTTTTGCGATTCTAAAGTGTAAAGA
TAAGAATTTCAATGGAACAGGAACATGTAAAAATGTCAGCACAGTACAGTGTACACATGGAATTAGACCA
GTAGTATCAACTCAACTGTTGTTAAATGGTAGTCTGGCTGAAGAAGAGGTAGTAATTAGATCTGCCAATT
TCAGTGACAATGCTAAAAACATAATAGTACAGCTGAACGAAACTGTAGAAATTAATTGTACAAGACCCAA
CAACAATACAATGAAAAAGCATACATATAGGACTAGGAGAGCATTTTATACAACAGGACAAATAATAGGA
GATATAAGAAAAGCACATTGTAGCATTAATATGACAAAATGGAATAACACCTTAATACAGGTAGCTAAAA
AGTTAGGAGAACAATTTAAGAATAAAAAACAAGTCTTTAACCAATCCTCAGGAGGGGACACAGAAATTGT
AATGCACAGCTTTAATTGTGGAGGGGAATTTTTCTACTGCAATACAACACACTGTTTTAATGGTAGTTGG
AATCCAAATGGTACTTGGAATTATGCTGGGGGGTCAAACGACACTATCACACTCCCATGCAGAATAAAAC
AAATTATAAAATATGTGGCAGGAAGTAGGAAAAGCAATGTATGGCCCTCCCGTCAAAGGACAATCAGATG
TGTATCAAACATTACAGGGTTGATATTAACAAGAAGATGGTGGTAATGGTGGTAATGCACAGACAACACC
ACCGAGACCTTTAGGCCTGCAGGAGGAAATATGAAGGACAATTGGAGAAGTGAATTATATAAATATAAAG
TAGTAAGAATTGAACCATTAGGAGTAGCACCCACTAAGGCAAAGAGAAGAGTGGTACAAAGAGAAAAAAG
AGCAGTGGGAATGGGAGCTCTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-031_2c10;PRT/1;HIV-1>
SATEQLWVTVYGVPVWWKEANTTLFCASDAKAYKTEVHNVWATHACVPTDPNPQEVLLPNMTEDFNMWKN
NMVEQMHEDIISLWDQSLKPCVKLTPLCVTLKCTDLNTTNTINSSLMEKSGEIKNCSFNITTNIRDKMQK
DYALFYRLDVVPIDNDNTSYRLISCNTSVITQACPKVSFEPIPIHCCAPAGFAILKCKDKNFNGTGTCKN
VSTVQCTHGIRVVVSTQLLLNGSLAEEEVVIRSANFSDNAKNIIVQLNETVEINCTRPNNNTMKSIHIGL
GRAFYTTGQIIGDIRKAHCSINMTKWNNTLIQVAKKLGEQFKNKTIVFNQSSGGDTEIVMHSFNCGGEFF
YCNTTQLFNGSWNPNGTWMUAGGSMDTITLPCRIKQIINMWQEVGKAMYAPPVKGQIRCVSNITGLILTR
DGGNGGNGTDNTTEIFRPAGGNMKDNWRSDAELYKVVRIEPLGVAPTKAKRRVVQREKR
<U-064c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCCATGGAGTGAAGGGGGATCAGGAGGAATTTGTCAGCACTTATGAGATG
GGGCACCATGCTCCTTGGGATGTTAATGATCTGTAGTGCTACAGAACAATTGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGGAAAGAAGCAACTACCACCCTATTTTGTGCATCAGATGCTAAAGCATATGATACAG
AGAGACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCTGCCCACAAGAAGTAGGATTGGG
AAATGTGACAGAGTATTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGATATAATCAGT
TTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACACCACTCTGTGTTACTTTAAATTGTAATGCGG
GAAAGTTTAATTATACGAATAATACTGATACACTGAAAGAAGAAGTAGGAGAAATAAAAAACTGCTCTTT
CAATATCACCACAAGCATAAGAGATAAGGTAAAGAAAGAATATGCATTTTTTAATAAACTTGATGTAGTA
CCAATAGATAATGAGAATGATAGCTATAGGTTGATAAGTTGTAACACCTCAGTCATTACTCAGGCCTGTC
CAAAGGTATCATTTGAGCCAATTCCTATACATTATTGTGCCCCAGCTGGTTTTGCGATTCTAAGGTGTAA
TAATAAGACATTCAATGGGACAGGACCATGTACAAATGTCAGTACAGTACAATGTACACATGGAATTAGG
CCAGTAGTGTCAACCCAACTGCTGTTAAATGGCAGTCTAGCAGAAGAGGAGGTAATGATTAGGTCTGAGA
ACTTCACGAACAATGCTAAAACCATAATAGTCAGCTAGAATGAATCTGTAGTAATTAATTGTACAAGACC
CAACAACAATACAAGAAAAAAGTATACACATAGGACCAGGGAGAGCATTTTATACAACAGGAGAATAATA
GGAGATATAAGAAAAGCACATTGTAACATTAGTAAAGCAAAATGGGATAGCACTTTAAAACAAGTAGTTA
CAAAATTAAGAGAACAATATGGAAATAAAACAATAGCCTTTAAGAACTCCTCAGGAGGGGACCCAGAAAT
TGTAATGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGTAATACAACAAAGCTATTTAATAGTACT
TGGAATAGGACAGAGGTAGATACTATTGAAGGAAATACCACTATAAATATCACACTCCCATGTAGAATAA
AACAAATTATAAACATGTGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATCAGAGGACCAATTAT
CTGCACATCAAATATTACAGGGCTGCTGTTAATAAGAGATGGTGGTACAGACAATAGCACGAACGACACC
GAGATCTTCAGACCTGGAGGAGGAGATATGAGGGACAATGGAGAAGTGAATTATACCAAATATAAAGTAG
TAAAAATTGAACCATTAGGAATAGCACCCACCAAGGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAAGAGC
AATAGGAATAGGAGCTGTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-064c1;PRT/1;HIV-1>
SAIQLWVTVYYGVPVWKEATTTLFCASDAKAYDTERHHNVWATHACVPTDPCPQEVGLGNVTEYFNMWKN
NMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCNAGKFNYTNNTDTLKEEVGEIKNCSFNITTSIRDKVK
KEYAFFNKLDVVPIDNENDSYRLISCNTSVITQACPKVSFEPIPIHYCAPAGFAILRCNNKTFNGTGPCT
NVSTVQCTHGIRPVVSTQLLLNGSLAEEEVMIRSENFTNNAKTIIVQLNESVVINCTRPNNNTRKSIHIG
PGRAFYTTGEIIGDIRKAHCNISKAKWDSTLKQVVTKLREQYGNKTIAFKNSSGGDPEIVMHSFNCGGEF
FYCNTTKLFNSTWNRTEVDTIEGNTTINITLPCRIKQIINMWQEVGKAMYAPPIRGPISCTSNITGLLLI
RDGGTDNSTNDTEIFRPGGGDMRDNWRSELYKYKVVKIEPLGIAPTKAKRRVVQREKR
<U-099c6;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAAAGTGACGGGGATCATGAAGAATTATCAGCACTTATGGAGATG
GGGCATCATGCTCCTTGGGATGTTGATGATCTATAGTACTGCAGAACAACAATTGTGGGTCACAGTCTAT
TATGGGGTACCTGTGTGGAAAGAAGCAACTACTACTCTATTCTGTGCATCAGATGCTAAAGCATATGATA
CAGAGGTACATATGTTTGGGCCACACATGCCTGCTGTACCCACAGACCCCAACCCACAAGAAGTAGTATT
GGGGAATGTGACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGATATAATC
AGTTTATGGGATCAAAGCCTAAAACCATGTGTAAAACTAACCCCACTCTGTGTTACTTTAAATTGCACTG
ACTGGGATAAAACGAATTGCACTAATGGGGGAGATATTACTGCTAATGAGGAAAAAGGAGAACTAAAAAA
TTGCTCTTTCAATATCACCACAAACATAAGAGATAAGATACGGAAAGAATATGCACTTTTTTATAAATTG
GATGTAGTACCAATAGATAATGATAATACTAGTTATAGGTTGATAAATTGTAACACCTCAGTCATTACAC
AAGCCTGTCCAAAGGTATCCTTTGAGCCAATTCCCATACATTTATTGTGCCCGGCTGGTTTTGCGATTCT
AAAGTGTAACAATAAGACGTTCAATGGAAAAGGACCATGTAAAAATGTCAGCACAGTACAATGCACACAT
GGAATTAGGCCAGTAGTGTCAACTCAACTGCTGTTAAATGGCAGTTTAGCAGAAGAAGAGGTAGTAGTTA
GATCTGCCAATTTCTCGGACAGTGCCAAAACCATCCATAGTACAACTAATGAATCTGTAGTAATTAATTG
TACAAGACCCAACAACAATACAAGAAAAAGCATACATATAGGACCAGGGAGAGCATTTTATGCAACAGGA
GAAATAATAGGAGATATAAGACAAGCACATTGTAATCTTAGTCTAACAAAATGGAATCAAACTTTATATC
AGGTAGTTAGAAAATTAAAAGAACAATTTAAGAATAAAACAATAGCCTTTAATCACTCCTCAGGAGGGGA
CCCAGAAATTGTAATGCACAGTTTTAATTGTGGAGGAGAATTTTTCTACTGTAATACAACACAATTATTT
AATAGTACTTGGTATACTAATGGTACTTGGAGTGATACTGGAAGTAATGACACAGTCACACTCCCATGCA
GAATAAAACAAATTATAAACAGGTGGCAAGAAGTAGGAAAAGCAATTATGGCCCCTCCCATCAAAGGACA
AATTAGATGCTCATCAAATATTACAGGGCTGTTATTAACAAGAGATGGTGGTAGTAGCAAAAACGAGACC
GAGGTCTTCAGACCTGGAGGAGGAGATATGAGGGACAATTGGAGAAGTGAATTATATAAATATAAAGTAG
TAAAAATTGAACCATTAGGAGTAGCACCCACCAGGGCAAAGAAGAAGAGTGGTGCAGAGAGAAAAAGAGG
AATAGAGCTGTGTTCCTTGGTTCTTGGGAGCAGCAGGAAGCACT
<U-099c6;PRT/1;HIV-1>
STAEQQLWVTVYYGVPVWKEATTTLFCASAKAYDTEVHNVWATHACVPTDPNPQEVVLGNVVTENFNMWK
NNMVEQMHEDIISIWDDQLDPCVLTPLCVTLNCTDWDKTNCTNGGDITANEEKGEALKNCSFNITTNIRD
KIRKEYALFFYKLDVVPIDNDNTSYRLINNTSVITQACPKVSFEPIPIHYCAPAGFALLKCNNKTFNGKG
PCKNVSTVQCTHGIRPVVSTQLLLNGSLAEEVVVRSSANFSDSAKTIIVQLNESVVINCTRPNNNTRKSI
HIGPGRAFFYATGEIIGDIRQAHDNLSLTWNQTLYQVVRKLKEQFKNKTIAFNHSSGGDPEIVMHSFNCG
GEFFYCNTTQLFNSTWYTNGTWSDSTGSNTVTLPCRIKQIINRWQEVGKAMYAPPIKGQIRCSSNITGLL
LTRDGGSSKNETEVFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTRAKRRVVQREKR
<U-148_2c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGCGAAGGGGACCAAGAAGAATTGGCAGCAGCACTTATGGAA
ATGGGGCACGATGCTCCTTGGGATGTTAATGATCTGTAGTGCTGCGGAACAATGGTGGGTCACAGTCTAT
TATGGAGTACCTGTGTGGAAGGACGCAAATACCACTCTATTTTGTGCATCAGATGCTAAAGCATATGATA
CAGAGGCACATAATGTCTGGGCCACACATGCCTGTGTACCCACAGATCCCAACCCACAAGAAATAGTATT
GGAAAATGTGACAGAAGATTTTAACATGTGGAAAAATAACATGGCAGACCAGATGCATGAGGATATAATC
AGTTTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACTCCGCTCTGTGTTACTTTAAATTGTACTG
ATTGGAATGGTAATACTACTAGCAATAGTACTATAAACAACAATACTAGTACTAAGGCAGAAATGAAAAA
ATGCTCTTTTAATATCACCACAAGCATAAGAGATAAAGTGACAAAGGAATATGCACTGTTTTATAGAGTT
GATGTAGTACCAATAGATAAAGAAAATAATAAACTACCAATTATACCAATTATAGTTAATAATTGTAACA
CCTCAGTCATTACACAAGCCTGTCCAAAGACATCCTTTGAGCCAATTCCTATACATTATTGTGCCCCAGC
TGGTTTTGCAATTCTAAAGTGTAACAATAAGACATTCACAGGAAAAGGGACTGTACAAGGGTTAGCCACA
TTACAATGTACCACATGGAATTAGACCAGTATGTCAACTCAACTGCTGTTAAATGGCAGTCTAGCAGAAG
AGGAGGTAGTAATTGATGTGTGAAAATACACAGACAATGCTAAAACCATAATAGTACAGCTGAATGAATC
TGTAGCAATTAATTGTACAAGACCTAATAACAATACAAAGAAAAGTATACCTATAGGACCAGGGAGAGCA
TTTTATGCAACAGGAGATATAGTAGGAAATATAAGACAAGCACATTGTAACCTTAGTGGAACAGAGTGGG
AAAAAACTTTAGGGAAAATAGTTGGGGAATTAAGAAAAATTTTGAGAATAAGACAATAATTTTTTAATCA
ATCCTCAGGAGGGGACCCAGAAATTGTATCGCACCTTTTTTAATTGTGGAGGGAATTTTTCTATTGTAAC
TCAACACAACTGTTTAATAGTACTTGGAATACTACTGCAAAAATTGATGGTTCTGGGAATGTTACTGGAA
AGGTAAATAGCACTATCACACTCCAATGTAAAATAAGACAAATTGTAAACCTGTGGCAGGAAGTAGGAAA
AGCAATGTATGCCCCTCCCATCAGTGGAATAATTTACTGTTCATCAAATATTACAGGGCTGATACTGATG
AGAGATGGTGGTAATGATAGTAGCACGAATGGAAACGAGACCTTCAGACCTGGAGGGGGAAATATGAAAG
ATAATTGGAGAAGTGAATTATATAAAATATAAAGTAGTAAAAATTGAACCATTAGGACTAGCACCACCAA
GGCAAAGAGGAGAGTGGTGCAAAGAGAAAAAAGAGCAGTAGGAATAGGAGCTATGTTCCTTGGGTTCTTG
GGAGCAGCAGGAAGCACT
<U-148_2c1;PRT/1;HIV-1>
SAAEQWWVTVYYGVPVWKDANTTLFCASDAKAYDTEAHNVWATHACVPTDPNPQEIVLENVTEDFNMWKN
NMADQMHEDIDISLWDQSLKPCVKLTPLCVTLCTDWNGNTTSNSTINNNTSTKAEMKKCSFNITTSIRDK
VTKEYALFYRVDVVPIDKENNTNYTNYRLINCNTSVITQACPKTSFEPIPIHYCAPAGSFAILKCNNKTF
TGKGLCTRVSTLQCTHGIRPVVSTQLLLNGSLAEEEVVIRCENITDNAKTIIVQLNESVAINCTRPNNNT
RKSIPIGPGRAFYATGDIVGNIRQAHCNLSGTEWEKTLGKIVGELRKNFENKTIIFNQSSGGDPEIVSHL
FNCGGEFFYCNSTQLFNSTWNTTAKIDGSGNVTGKVNSTITLQCKIRQIVNLWQEVGKAMYAPPISGIIY
CSSNITGLILMRDGGNDSSTNGNETFRPGGGNMKDNWRSELYKYKVVKIEPLGLAPTKAKRRVVQREKR
<U-183_2c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGGATCAGGAAGAATTGGCGGCGCTGGTGGAGATG
GGGCACCATGCTCCTTGGGATGTTAATGATCTGTAGTGCTACAGAACAATTGTGGGTTACAGTCTATTAT
GGGGTACCTGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATCAGATGCTAAAGCATATAATACAG
AGGTACGTAATGTATGGGCCACACATGCCTGTGTGCCCACAGGCCCCAACCCACAAGAAATAGTATTGGT
AAATGTGACAGAAGATTTTAACATGTGGAAAAATAGCATGGTAGAACAGATGCATGAGGATATAATCAGT
TTATGGGATCAAAGCCTAAAACCTTGTGTAAAATTAACCCCACTCTGTGTTACTTTAAACTGCACTGATT
TGAGGAATACTACTAATAGCACTAATAGTGACGGGGAAAAGATGGAGAGAGGAGAAATAAAAAACTGCTC
TTTCAATGTTACCACAGGCATAAGAGATAAGGTTCAGAGAGAATATGCACTCTTTTATAAACTTGATATA
GTACCAATAGAGGAAGGTGGGGATAATACCAGCTGTAGGGATAATACCAGCTATAGGTTGATAAGTTGTA
ATACCTCAGTCATTACACAAGCCTGTCCAAAGGTATCCTTTGAGCCAATTCCCATACATTATTGTGCCCC
AGCTGGTTTTGCGATTCTAAAGTGTAATAATAAGACGTTCAATGGAAAAGGACCATGTTCAAATGTCAGC
ACAGTACAATGTACACATGGAATTAGGCCAGTAGTGTCAACTCAACTGCTGTTAAACGGCAGTCTAGCAG
AAAAAGAGGTAGTAATTAGATCTGAAAATATCACGGACAATACTAAAAACATAATAGTACAGTTAAATGA
AACTGTAGAAATTAATTGTACAAGACCCAACAACAATACAAGAAAAAGTATACATATAGGACCGGGGAGA
GCATTTCATGCAACAGGAGAAATAATAGGAAATATAAGACAGGCATATTGTAACATTAGTGGAGCAAAAT
GGAATAACACTTTAAAACAGATAGTAAAAAGATTAAAAGAAAAATTTCCGAATAAGATAATAGTCTTTAA
TCACTCCTCAGGAGGGGACCCAGAAATTGTAACACACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGT
AATTCAACAAACCTGTTTAATAGTAATTCAACACAACTGGATAATTGGACTTATACTGAAGGGTCAAATG
ACACTGTTATCACGCTCCCATGCAGAATAAAACAAATTGTAAATATGTGGCAGGAAGTAGGAAAAGCAAT
GTATGCTCCTCCCATCAGAGGACAAATTAGATGTTCTTCAAATATTACAGGGCTGATATTAACAAGAGAT
GGTGGTAATAAGACTGACAATGACACCACCGAGACCTTCAGACCTGGAGGAGGAAGCATGAGGGACAATT
GGAGAAGTGAATTATATAAATATAAAATAGTAAAGGTTGAACCATAGGAGTAGCACCCACCAAGGCCAAA
GAGGAGAGTGGTGCAGAGAGAAAAAAGAACAGTGGGACTGGGAGCCTTGTTTCTTGGGTTCTTGGGAGCA
GCAGGAAGCACT
<U-183_2c1;PRT/1;HIV-1>
SATEQLWVTVYYGVPVWKEATTTLFCASDAKAYNTEVRNVWATHACVPTGPNPQEIVLVNVTEDFNMWKN
SMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCTDLRNTTNSTNSDGEKMERGEIKNCSFNVTTGIRDKV
QREYALFYKLDIVPIEEGGDNTSCRDNTSYRLISCNTSVITQACPKVSFEPIPIHYCAPAGFAILKCNNK
TFNGKGPCSNVSTVQCTHGIRPVVSTQLLLNGSLAEKEVVIRSENITDNTKNIIVQLNETVEINCTRPNN
NTRKSIHIGPGRAFHATGEIIGNIRQAYCNISGAKWNNTLKQIVKRLKEKFPNKIIVFNHSSGGDPEIVT
HSFNCGGEFFYCNSTNLFNSNSTQLDNWTYTEGSNDTVITLPCRIKQIVNMWQEVGKAMYAPPIRGQIRC
SSNITGLILTRDGGMKTDNDTTETFRPGGGSMRDNWRSELYKYKIVKVEPLGVEPTKAKRRVVQREKR
<U-209c3;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGGATCAGGAAGAATTATCAGCACTTGTGGAGAGG
GGACAACTTGTGGAGAGGGGGCATCATGCTCCTTGGGATATTGATGATCTGTAGTGCTACAGAAAAATTG
TGGGTCACAGTCTATTATGGGGTACCTGTGTGGAAAAATGCAAACACCACTCTATTTTGTGCATCAGATG
CTAAAGCATATGATACAGAGGTACATAATGTTTGGGCCACACACGCCTGTGTACCCACAGACCCCAGCCC
ACGAGAATTAATATTGGAAAATGTGACAGAAGACTTTGACATATGGAAAAATAACATGGTAGAACAGATG
CAAGAGGATATAATCAGTTTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCTCTCTGTGTTA
CTTTAGAATGCAAGAATGCCACTAAAATTAGTAATAGCAGTGAAATTGGAGAAATGAAAAAATGCTCTTT
TAATGTTACCACAGACAGGAGAGATAATGGTGAAAACAGAATATGCACTTTTTATAACCTTGATATAATA
CAAATAGAGGAGGAGAATACCAGCAGCTGCAGTAATACCAGCAGCCTCAGGTTGATAAGTTGTAACACCT
CAACCCTTACACAGGCCTGTCCAAAGATATCCTTTGAGCCAATTCCCATACATTATTGTGCCCCGGCTGG
TTTTGCAATTCTAAAGTGTAATAATAAAACATTCGATGGAAAAGGATCATGTAAAAATGTCAGCACAGTA
CAATGTACACATGGAATTAAGCCAGTAGTATCAACTCAACTGCTGCTAAACGGCAGTCTAGCAGAAGAAG
AGGTAGTAATTAGATCTGCTAATCTCTCAGACAATGCTAAAACCATAATAGTACAGCTGAACATGTCTGT
ACAAATTAATTGTACAAGACCCAACAACATACAAGAAGAGGTATACATTTAGGACCAGGGGAGAGCCTTT
TATGGAACAGACATAATAGGAGATATAAGACAAGCACATTGTAACATTAGTGGAAAACAATGGAATTACA
CTTTACAACAGATAGTTAAAAAATTCAGAAAACAATTTGAGAATAGCACAGTGATCTTTAACAGATCCTC
AGGAGGGGACCCAGAAATTGTAATGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGTAATACAACA
GAACTGTTTAATAGTACTTGGAACAGTAGTCATCCTTTGGATGATACTTGGCCTCCTTTGGATAATACAA
GTGACACTACTATCACACTCCCATGCAGAATAAAACAAATTATAAACATGTGGCAGGAAGTAGGAAAAGC
AATGTATGCCCCTCCCATCAAAGGACCAATTAGATGTGAATCAAATATTACAGGGCTGCTATTAACAAGA
GATGGTGGCGATACCAATACCACTAACGGGACTGAGACCTTCAGACCTGGAGGAGGAGATATGAGGGACA
ATTGGAGAAGTGAATTATATAAATATAAAGTAGTAAGAATTAAACCATTAGGAATAGCACCCACCAAGGC
ACAGAGAAGAGTGGTGCAAAGAGAAAAAAGAGCAGCACTAGGAGCTATGTTCCTTGGGTTCTTGGGAGCA
GCAGGAAGCACT
<U-209c3;PRT/1;HIV-1>
SATEKLWVTVYYYGVPVWKANTTLFCASDAKAYDTEVHNVWATHACVPTDPSPRELILENVTEDFDIWKN
NMVEQMQEDIISLWDQSLKPCVKLTPLCVTLECKNATKISNSSEIGEMKNCSFNVTTDRRDKVKTEYALF
YNLDIIQIEEENTSSCSNTSSYRLISCNTSTLTQACPKISFEPIPIHYCAPAGFAILKCNNKTFDGKGSC
KNVSTVQCTHGIKPVVSTQLLLNGSLAEEEVVIRSANLSDNAKTIIVQLNMSVQINCTRPNNNTRRGIHL
GPGRAFYGTDIIGDIRQAHCNISGKQWNYTLQQIVKKFRKQFENSTVIFNRSSGGDPEIVMHSFNCGGEF
FYCNTTELFNSTWNSSHPLDDTWPPLDNTSDTTITLPCRIKQIINMWQEVGKAMYAPPIKGPIRCESNIT
GLLLTRDGGDTNTTNGTETFRPGGGDMRDNWRSELYKYKVVRIKPLGIAPTKAQRRVVQREKR
<U-212c11;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGACAGTGATGGGGATCAGGAGGAATTATCAATGCTTGTGGAAATG
GGGCATGACGCTCCTTGGGATGTTGATGATCTGTAGTGCTGCACAATTGTGGGTCACAGTCTGTTATGGG
GTACCGGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATCAGATGCTAAAGCATATGACACAGAGG
TACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAATCCACTAGAATTAAAATTGGATAA
TGTGACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGAACAAATGCATGAGGATATAATCAGTTTA
TGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCACTCTGTGTTACTTTAAATTGCACTGACTACT
CGAAGAATGGTACTAATAAGACTGCTAATAATGAAGGAGAAATGAAAAACTGCTCTTTTAATATCACCAC
AAACATAAGAGATAAGATGCAGAATGAATACGCACTTTTTTATAAACATGATATGGTATCAATAGATAAT
AGTAGTACTAGCTATAGGTTGACAAGTGTAACACCTCAGTCATTACACACAGGCCTGTCCAAGATAACCT
TTGAACCAATTCCTATACATTATTGTACCCCGGCTGGTTTTGCGCTTTTAAAGTGTAATAATAAAACGTT
CAATGGAACAGGACCATGTAAAAATGTCAGCACAGTACAATGTACACATGGAATTAGGCCAGTAGTTTCA
ACTCAACTGCTGTTAAATGGCAGTCTAGCAGAAGAAGAGGTAGTAATTAGATCTGAAAATTTCACGAACA
ATGCAAAAATCATAATAGTACAGCTAAATGAAACTATACAAATTAATTGTACAAGACCCAACAACAATAC
AAGAAAAAGTATACATATAGCACCAGGGAGAGCATTTTATGCAACAGGAGAAATAATAGGAGATATAAGA
CAAGCACATTGTAACATTAGAGCAGAATGGAACAACAACGCTTTAAAACAGATAGTTGAAAAATTAAGAG
AACAATTTAAGAATAAAACAATAGAATTTAAGTCATCCTCAGGAGGGGACCCAGAAATTGTAATGCACAG
TTTCAATTGTGGAGGGGAATTTTTCTACTGTAATTCAACAAAACTGATTAATAGTATTTGGTATCCGAAT
GGTACTGAAGGGTCAAATAACACTGAAGGAAATGACCCAATCACACTCCCATGCAGAATAAGACAAATTG
TAAACAGATGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATCAGGGGACCAATTAGATGTTCATC
AAATATTACAGGGCTGCTATTAACAAGAGATGGTGTGCTAATAATTACTGATAATGAGACCTTCAGACCT
GGAGGAGGAGATATGAGGGACAATTGGAGAAGTGAATTATATAAATATAAAGTAGTAAGAATTGAACCAT
TAGGAATAGCGCCCACTACGGCAAGGAGAAGAGTGGTGCAAAGAGAAAAAAGGGCAGCCATAGGAGCTAT
GATCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-212c11;PRT/1;HTV-1>
SAAQLWVTVCYGVPVWKEATTLFCASDAKAYDTEVHNVWATHACVPTDPNPLELKLDNVTENNFNMWKNN
MVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCTDYSKNGTNNTANNEGEMKNCSFNITTNIRDKMQNEYA
LFYKHDMVSIDNSSTSYRLTSCNTSVITQACPKITFEPIPIHYCTPAGFALLKCNNKTFNGTGPCKNVST
VQCTHGIRPVVSTQLLLNGSLAEEEVVIRSENFTNNAKIIIVQLNETIQINCTRPNNNTRKSIHIAPGRA
FYATGEIIGDIRQAHCNISRAKWNNALKQIVEKLREQFKNKTIEFKSSSGGDPEIVMHSFNCGGEFFYCN
STKLFNSIWYPNGTEGSNNTEGNDPITLPCRIRQIVNRWQEVGKAMYAPPIRGPIRCSSNITGLLLTRDG
GANNTDNETFRPGGGDMRDNWRSELYKYKVVRIEPLGIAPTTARRRVVQREKR
<U-294c30;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAAAGTGAAGGGGATCAGGAAGAATTGTCAGCGCTGGTGGATAGG
GGGCATCTTGCTCCTTGGAATGTTGATGATCTGTAGTGCTGCAGAACAATTGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGGAAAGAAGCAAACATCACTCTATTTTGTGCATCAGATGCTAAGGGATATGATACAG
AAGCACATAATGTCTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAGGTAGCATTGAC
AAATGTGACAGAAAACTTTAACATGTGGAAAAATAACATGGTAGAACAAATGCATGAGGATATAATTAGT
TTATGGGATCAAAGCTTAAAGCCATGTGTAAAATTAACCCCACTCTGTGTTACTTTAGATTGCAATGATA
CTAATATAAATGTAACTAGCAAAAAAATGAGAATGATGGAGCAAGGAGAAGCAAAAAACTGCTCTTTCAA
TATCACCACAAATTTAAGAGATAAGGTGCAGAAAGAATATTCAGTTTTTTATAAACTTGATGTAGTACCA
ATAGAAGAGGAGAAAAATAATAGTATTAACAATAGATATAGGTTGATAAGTTGTAACACCTCAGTCATTA
CACAAGCCTGTCCAAAGATATCCTTTGAACCAATTCCCATACATTATTGTGCCCCGGCTGGTTTTGCGAT
TCTGAAGTGTAACAATAAGACATTCAGTGGAAAAGGACCATGCACAAATGTCAGCACAGTACAATGCACA
CATGGAATTAGGCCAGTAGTATCAACTCAACTGCTGTTAAATGGCAGCCTAGCAGAAGGAGAGATAGTAA
TTAGATCTGACAATAACACAGACAATACAAAAACCATAATAGTACAGCTGAATACATCTGTAGCAATTAA
TTGTACAAGACCCAACAACAATACAAGAAGAAGTATAACTATAGGACCAGGGAGAGCATTTTATGCAACA
GACATAATAGGAGATATAAGACAAGCACATTGTAACATTAGTAGAACACAATGGAATAACACTTTAAAAC
AGGTAGCTAGAAAATTAAGTGAACAATTTAATGCAACAATAGTTTTTAATAAATCCTCAGGAGGGGACCC
AGAAATTGTAATGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGTAATACAACACAACTGTTTAAT
AGTATTTGGTGTCCTAATAATACTGGAGAGTCAAATAGCACTAACAATGAGACAATCATACTCCCATGCA
GATTAAAACAATTTATAAACATGTGGCAGGAGGTAGGAAAAGCAATGTATGCCCCTCCCATCAGAGGATA
CATTAACTGTTCATCAAATATTACGGGGCTGCTATTAACAAGAGATGGTGGTGGTGATAATAAAAACACG
AGTCCAGAGAACAAGACAGAGACCTTCAGACCTGGAGGAGGAAATATGAAGGACAATTGGAGAAGTGAAC
TGTATAAATATAAAGTAGTAAGAATTGAACCATTAGGAGTAGCACCACCAAGGCAAAAGAGAAGAGTGGT
GCAGAGAGAAAAAAGAGCAGTGGGAATAGGAGCTATGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-294c30;PRT/1;HIV-1>
SAAEQLWVTVYYGVPVWKEANITLFCASDAKGYDTEAHNVWATHACVPTDPNPQEVALTNVTENFNMWKN
NMVEQMHEDIISLWDQSLKPCVKLTPLCVTLDCNDTNINVTSKNETMMEQGEAKNCSFNITTNLRDKVQK
EYSVFYKLDVVPIEEEKNNSINNRYRLISCNTSVITQACPKISFEPIPIHYCAPAGFAILKCNNKTFSGK
GPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEGEIVIRSDNFTDNTKTIIVQLNTSVAINCTRPNNNTRRS
ITIGPGRAFYATDIIGDIRQAHCNISRTQWNNTLKQVARKLSEQFNATIVFNKSSGGDPEIVMHSFNCGG
EFFYCNTTQLFNSIWCPNNTGESNSTNNETIILPCRLKQFINMWQEVGKAMYAPPIRGYINCSSNITGLL
LTRDGGGDNKNTSPENKTETFRPGGGNMKDNWRSELYKYKVVRIEPLGVAPTKAKRRVVQREKR
<U-307c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAAAGCGAAGGGGACCAGGAAGAATTATCAGCACTTGTGGAGATG
GGGTACCATGCTCCTTGGGATGTTGATGATCTGTAGTGCTACAGAGCAATTGTGGGTAACAGTCTATTAT
GGGGTACCTGTGTGGAAAGAAGCAAAAACCACTCTATTTTGTGCATCAGATGCTAAAGCATATGATACAG
AGATGCATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAATAGTATTGGA
AAATGTGACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGATCAGATGCAGGAGGATGTAATCAGT
CTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCACTCTGTGTTACTTTAAATTGCAATGATA
CATTGAGGAATGATAATAGCACTAAGAATAATAGTAGTACTGGTTGGGAAAAGATGGAGAAAGGAGAAAT
AAAAAATTGCTCTTTCAGTGCCACCACAACCGTGAAAGATAAGACACAGAAACAATATGCACTTTTTTAT
AATCTTGATATAGTACATACAAATGATGGTGGTAATAGTAGCTATATGTTAACAAGTTGTAACACCTCAG
TCATTACACAGGCCTGTCCAAAGGTATCATTTGAGCCAATTCCCATACATTATTGTGCCCCGGCTGGTTT
TGCGATTCTAAAGTGTAATGATAAGAAGTTCAATGGGACAGGACCATGTAAAAATGTCAGCACAGTACAA
TGTACACATGGAATTAGGCCAGTAGTGTCAACTCAACTGCTATTAAATGGCAGTCTAGCAGAAGAAGAGG
TAGTAATTAGATCTAGCAATTTAACGGACAATACTAAAACCATAATAGTACAGCTGAAGGAATCTGTAAA
AATTAATTGTACAAGACCCAACAACAATACAAGAAAAAGTATATCTATAGGACCAGGGAGCGCATTTTAT
GCAACAGGAGACATAATAGGAGATATAAGACAAGCACATTGCAACCTTAGTAAAACAGAATGGGGGGAAA
CTTTAAGACAGATAGCTACAAAATTAAGAGAACAATTTAATAATAAAACAATAATCTTTAATAGCTCCTC
AGGAGGGGACCCAGAAATTGTAATGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGTAATACAACA
AAACTGTTTAATGGTACTTGGAATGGTACTTGGAAGAATGGTACTTGGAGTACAAATGATACTGAAAATG
ATACTATCATACTCCCATGTAGAATAAAACAAATTATAAACATGTGGCAGGAAGTAGGAAAAGCAATGTG
TGCCCCTCCCATCAGAGGACAAATTAACTGCTCATCACAGATTACAGGGCTGCTATTAACAAGAGATGGT
GGAGATAACCCTAAAAATGAAACCTTCAGACCTGGAGGAGGAGATATGAGGGACAATTGGAGAAGTGAAT
TATATAAATATAAAGTAGTAAAAATTGAACCATTAGGAATAGCACCTACCAGGGCAAAGAGAAGAGTGGT
GCAGAGAGAAAAAAGAGCAGCAATAGGAGCTATGATCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-307c1;PRT/1;HIV-1>
SATEQLWVTVYYGVPVWKEAKTTLFCASDAKAYDTEMHNVWATHACVPTDPNPQEIVLENVTENFNMWKN
NMVDQMQEDVISLWDQSLKPCVKLTPLCVTLNCNDTLRNDNSTKNNSSTGWEKMEKGEIKNCSFSATTTV
KDKTQKQYALFYNLDIVHTNDGGNSSYMLRSCNTSVITQACPKVSFEPIPIHYCAPAGFAILKCNDKKFN
GTGPCKNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSSNLTDNTKTIIVQLKESVKINCTRPNNNTR
KSISIGPGSAFYATGDIIGDIRQAHCNLSKTEWGETLRQIATKLREQFNNKTIIFNSSSGGDPEIVMHSF
NCGGEFFYCNTTKLFNGTWNGTWKNGTWSTNDTENDTIILPCRIKQIINMWQEVGKAMCAPPIRGQINCS
SQITGLLLTRDGGDNPKNETFRPGGGDMRDNWRSELYKYKVVKIEPLGIAPTRAKRRVVQREKR
<U-312c4;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAGGGGGATTATGAGGAATTATCAGCACTTGTGGAGATG
GGGCATGACGCTCCTTGGGATGTTAATGATCAGTAGTGCTAATGAACAATTGTGGGTCACAGTCTGTTAT
GGGGTACCTGTGTGGAAAGAAGCAACCACTACTTTATTTTGTGCATCAGATGCTAAAGCATATGCTGCAG
AGAAACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTAGTAATAAA
TGTGACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGAGCAGATGCATGAAGATGTAACTAGTTTA
TGGGACCAAAGCCTAAAGCCATGTGTAAAATTAACCCCTCTCTGTGTTACTTTAAATTGCACTGACTATG
AGGGGAATAATATCACTAGTGGGAATAAGACAGGAGAAATAAAAAACTGCTCTTTCGAGATCACCACAAA
CATGAGAGATAAGATACAGAAAACATATGCACTTTTTTATAGACTTGATGTAGAACCAATAAATGATGAT
AATGTTACTTATAGGTTGATAAGCTGTAATACCTCAGTCATTACACAAGCCTGTCCAAAGGTAACCTTTG
AGCCAATTCCCATACATTATTGTGCCCCGGCTGGCTTTGCGATTGTAAAGTGTAACAATAAAACGTTCAA
TGGAACAGGACCATGTAAAAATGTTAGCACAGTACAATGTACACATGGAATTAGGCCAGTAGTATCAACT
CAACTGCTGTTAAATGGCAGTCTAGCGGAAGAAGAGACAATGATTAGATCTGAGAATTTCTCGGACAATG
CTAAAATCATAATAGTACAGCTGAATAAATCTGTAAAAATTAATTGTACAAGACCCAACAATAATACAAT
AAAAGGTATACATATAGGACCAGGGAGAGCATTTTATACAACAGGACAAATAATAGGAGACATAAGACAA
GCATATTGTACCATTAATAAAACAGAATGGAAATAACACTTTATCACAGATAGCTAAAAATTAAGTAGAC
AATTTGAGAATAAAACAATAGCCTTTAGGCCACCCTCAGGAGGGGACCCAGAAATTGTAATGCACAGTTT
TAATGTGGAGGGGGAATTTTTCTATTGTAATACAACACAACTGTTTAATAGTAATTGGACTACTAATGGA
GAGTCAAATTACACAACGGGAAACAATGAGACAATTATCACACTCCCATGCAGAATAAAACAATTTATAA
ACATGTGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATTAGTGGAATAATTAATTGCTTATCAAA
TATTACAGGGCTGCTATTAACAAGAGATGGTGGTAATAGTAGCAGCGCCAACAGCACCGAGATCTTCAGA
CCTGGAGGAGGGGATATGAGGGAATAATTGGAGAAGTGAACTATATAAATATAAAGTAGTACAAATGAAC
CATTAGGATTAGCACCCACCAAGGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCAGTGGGACTAGG
AGCTGTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-312c4;PRT/1;HIV-1>
SANEQLWVTVCYGVPVWKEATTTLFCASDAKAYAAEKHNVWATHACVPTDPNPQEVVINVTENFNMWKNN
MVEQMHEDVTSLWDQSLKPCVKLTPLCVTLNCTDYEGNNITSGNKTGEIKNCSFEITTNMRDKIQKTYAL
FYRLDVEPINDDNVTYRLISCNTSVITQACPKVTFEPIPIHYCAPAGFAIVKCNNKTFNGTGPCKNVSTV
QCTHGIRPVVSTQLLLNGSLAEEETMIRSENFSDNAKIIIVQLNKSVKINCTRPNNNTIKGIHIGPGRAF
YTTGQIIGDIRQAYCTINKTEWNNTLSQIAKKLSRQFENKTIAFRPPSGGDPEIVMHSFNCGGEFFYCNT
TQLFNSNWTTNGESNYTTGNNETIITLPCRIKQFINMWQEVGKAMYAPPISGIINCLSNITGLLLTRDGG
NSSSANSTEIFRPGGGDMRDNWRSELYKYKVVQIEPLGLAPTKAKRRVVQREKR
<U-313c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGAGATCAGGAAGAATTGTCAGAAATTCTGGAAATG
GGGCACCTTGCTCCTTGGGATGTTAATGATGATCTGTAGAGCTGCAGAGGATTCGTGGGTCACAGTCTAT
TATGGGGTACCTGTGTGGAAGGAAGCAACCACCACTCTATTTTGTGCATCAGATGCTAAAGCATATGACA
CAGAGGTACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCTAACCCACAAGAAGTAGTATT
GGAAAATGTGACAGAAAATTTCAATGCGTGGAAAAATAATATGGTAGAACAGATGCATGAGGATATAATC
AGTTTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCTCTTTGTGTTACTCTAAATTGCACTG
ATGTGAGAAATAATGCTACCAATACTACTAATACCAATAGTACTAATACCTATAGTACTAACATAGAAAA
GATGAAAGAAGGAGAAATAAAAAACTGCTCTTTCAATACCACCCCAAGCATAACAGACAAGATGCAGAAG
GCATATGCATTGTTTTATAAGTTGATATAGTACCAGAAAATAATGATAATAAAGATAATACCAGCTTATA
GATTGATAAGTTGTAATACCTCAGTCAATTACACAGGCCTGTCCAAAGCATCCTTTGAGGCAATTCCCAT
ACATTATTGTGCCCCAGCTGGTTTTGCGATTCTAAAGTGTAATGATAAGAAGTTCAATGGAACAGGACCA
TGCAAAAATGTCAGCACAGTACAATGTACACATGGAATTAGGCCAGTAGTATCAACCCAACTGCTGTTAA
ATGGCAGTCTAGCAGAAGAAGAGGTAGTAATTAGATCTGAAAATTTCACAAACAATGCTAAAACCATAAT
AGTACAGCTGAATGAGACTGTACATATTAATTGTACAAGACCCAACAACAATACAAGAAAAAGTATAGGT
ATAGGACCAGGGAGAACATTTTTTGCAACAGGGGAAATAATAGGAGACATAAGACAAGCACATTGTAACA
TTAGTAGAAACAACTGGAATAAAACTTTAGGTAGGGTAGTTAAAAAATTAAGAGAACAATTTGGGAACAA
CAAAACAATTGTTTTTAATCAATCCTCAGGAGGGGACCCAGAAATTGTGATGCACAGTTTTAATTGTAGA
GGAGAATTTTTCTACTGTAATACAACACAACTGTTTAATAGTACTTGGAATGCTAATAGTACTTGGAATG
CTAACGAGAATACTACTGGAATGCCAAGTGACAATATCACACTCCCCTGCAGAATAAAACAAGTTATAAA
CATGTGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATTAAAGGACCAATTAAGTGTTCATCAAAT
ATTACAGGACTGCTATTAACAAGGGATGGTGGTGTGAACAATTCTGAAACTGAGACCTTCAGACCTGGAG
GAGGAGATATGAGGAACAATTGGAGATGTGGATTATATAAATATAAAGTAGTAAAAATTGAGCCATTAGG
AGTAGCACCCACCAGGGCAAAGAGAAGAGTGGTGCAAAGAGAAAAAAGAGCAGTGGGACTAGGAGCTATG
TTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-313c1;PRT/1;HIV-1>
RAAEDSWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHACVPTDPNPQEVVLENVTENFNAWKN
NMVEQMHEDIISLWDQSLKKPCVKLTPLCVTLNCTDVRNNATNTTTNSTNTYSTNIEKMKEGEIKNCSFN
TTPSITDKMQKAYALFYKLDIVQINNDNKDNTSYRLISCNTSVITQACPKASFEPIPIHYCAPAGFAILK
CNDKKFNGTGPCKNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSENFTNNAKTIIVQLNETVHINCT
RPNNNNTRKSIGIGPGRTFFATIIIGDIRQAHCNISRNNWNKTLERVVKKLREQFGNNKTIVFNQSSGGD
PEIVMHSFNCRGEFFYCNTTQLFNSTWNANSTWNANENTTGMPSDNITLPCRIKQVINMWQEVGKAMYAP
PIKGPIKCSSNITGLLLTRDGGVNNSETETFRPGGGDMRNNWRCGLYKYKVVKIEPLGVAPTRAKRRVVQ
REKR
<U-317_2c1;DNA;HIV-1>
AGAAAGAGCAGAGACAGTGGCAATGAAAGTGAAGGGGATCAGGAAGAATTATCAGCACTTGTGGGGATGG
GGCATGATGCTCCTTGGGATGTTAATGATCTGTAGTGCTACAGAAAACCTGTGGGTCACAGTATATTGTG
GGGTACCTGTGTGGAAAGAAGCAGAAACCAGTCTATTTTGTGCATCAGATGCTAACACATATAATACAGA
GGCTCATAATGTTTGGGCCACTCATGCCTGTGTACCCACGGACCCCAACCCACAAGAAATATATTTGGAA
AATGTGACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGATATAGTAAGTT
TATGGGATGAAAGCCTAAAGCCATGTGTAAAAATAACCCCACTCTGTGTCACTCTAAATTGCACTGATTT
GGAAAATGGCACTAGTAGCAATAATAGTAGCTATCAAAGGGGGGAAGAAGGAGAAATAAAGAACTGCTCT
TTCAATATCACCACAAGATTAAGAGAAAAGGTACAGAAAGAATATGCACTTTTTTATAAACTTGATATAA
TAGCAATGGATAATAAAACTAATGCTACCAGATATAGGTTGATAAGTTGTAACACCTCAACCATTACACA
GGCCTGTCCAAAAGTATCCTTTGAGCCAATTCCATACATTATTGTGCCCCAGCTGGTTTTTGCGCTTTTC
AAGTGTAATGATAAGAAGTTCAATGGATCAGGAACATGTAACAATGTCAGCACAGTACAATGTACACATG
GAATTAGGCCAGTAGTATCAACTCAGCTGTTGCTAAATGGCAGTCTAGCAGAAGAAGAGGTAGTAATTAG
ATCTGAAAATTTCACAAACAGTGCTAAAACCATAATGTACAGCTAAAAGAACCTGTAAAAAATTAATTGT
ACAAGACCCAACAATAATACAAGAAGAAGTATACATATAGGACCAGGAAAAGCATTTTATGCAACAGGAG
AAATAATAGGAGATATAGGACAAGCACATTGTAACATTAGTGGACAAGAATGGAATAAAACTTTAATTCA
GATAGTTAAAAAATTGAGAGAACAATTTGGGAATAAGACGATAAACTTTACTAAACCAGCAGGAGGGGAC
CCAGAGATTGTAATGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGTGATACAACACGACTGTTTA
ATAGGGCTTGGAATAATACTGAAGAGTTAAATAGTACTACTGGAGAGTCAAATAACACTATCACCCTCCC
ATGCAGAATAAAACAAATTATAAACATGTGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATCCAA
GGAACAATTAGATGTTCATCAAATATTACAGGGCTGCTACTAGCAAGAGATGGTGGCAGTAACAATGAGA
CTAATACTACTGAAATCTTCAGACCTGCAGGAGGAGATATGAGGGACAATTGGAGAAGTGAATTATATAA
ATATAAAGTAGTAAAAATTGAACCATTAGGAGTAGCACCCACCAGGGCAAAGAGAAGAGTGGTGCAAAGA
GAAAGAAGAGCAATAGGAATAGAGCTGTGTTCCTTGGGTTCCTTGGGAGCAGCAGGAAGCACT
<U-317_2c1;PRT/1;HIV-1>
SATENLWVTVYCGVPVWKEAETSLFCASDANTYNTEAHNVWATHACVPTDPNPQEIYLENVTENFNMWKN
NMVSQMHEDIVSLWDESLKPCVKITPLCVTLNCTDLENGTSSNNSSYQRGEEGEIKNCSFNITTRLREKV
QKEYALFYKLDIIAMDNKTNATRYRLISCNTSTITQACPKVSFEPIPIHYCAPAGFALFKCNDKKFNGSG
TCNNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSENFTNSAKTIIVQLKEPVKINCTRPNNNTRRSI
HIGPGKAFYATGEIIGDIGQAHCNISGQEWNKTLIQIVKKLREQFGNKTINFTKPAGGDPEIVMHSFNCG
GEFFYCDTTRLFNRAWNNTEELNSTTGESNNTITLPCRIKQIINMWQEVGKAMYAPPIQGTIRCSSNITG
LLLARDGGSNNETNTTEIFRPAGGDMRDNWRSELYKYKVVKIEPLGVAPTRAKRRVVQRERR
<U-343c3;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGGATCAGGAAGAATTGTCAGCACTTATGGAGATG
GGGCATCATGCTCCTTGGAATGTTAATGATCTGTAGTGCTGCAAGCCTGTGGGTCACAGTCTATTATGGG
GTACCTGTGTGGAAAGATGCAAACACCACTCTATTTTGTGCATCAGATGCTAAAGCATATGATACAGAGG
TACATAATGTGTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTAGTATTGGAAAA
TGTGACAGAAAATTTTAATATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGACATAATTAGTTTA
TGGGACCAAAGCCTAAAGCCATGTGTAAAACTAACCCCACTCTGTGTTACTTTAAATTGCACTGAGTTGA
TGTTGAATACTACTACCAATAGTACTACTACCAATAGTACCAGTAGTCCTCCTACCAGTAGTGGATTGAC
AAACTGCTCTTTCAATATCGCCACAGATCTAAGAGATAAGGTGCAGAAAGAATATGCTCTTTTTTCTACA
CTTGATGTAGTATCAATAGGTAATAACAGCTCTAGGCTGATAAGTTGTAACACCTCAATCCTTACACAGG
CCTGTCCAAAGGTATCCTTTGAGCCAATTCCCATACATTATTGTGCCCCGGCTGGTTTTGCAATTCTAAA
GTGTAACAATAAGACATTCAATGGAAAAGGACTATGTAACAATGTCAGCACAATACAATGTACACATGGA
ATTAAGCCAGTAGTATCAACTCAATTACTGTTAAATGGCAGTCTAGCAGAGAAAGACATAGTAATTAGAT
CTGACAATTTTTCAAACAATGCTAAGACCATAATAGTACAGCTGAAGAAGCCTGTATACATCAATTGTAC
AAGACCCAACAACAATACGAGAAAAGGTATACACATAGCACCAGGGAGAGCATTTTATACAACAGGACAG
ATAATAGGAGACATAAGGAAAGCATATTGTGAAATTAGTGGAAAAAGCTGGAATAACACTTTAGAACAGA
TAGCTACAAAATTAAGAGAACAATTTGGGAGTAATAAAACAATAGTCTTTAATCAATCCTCGGGAGGGGA
CCCAGAAATTGTAATGCACAGTTTTAATTGTAGAGGAGAATTTTTCTATTGTAATTCAACACAATTGTTT
AATAGTACTTGGCCGGGTAACGGTCCTAGCAATAATACTACTGGGAATGGTACTGATACTGTTATCATCC
TTCCATGCAGAATAAAACAAATCATAAACATGTGGCAGGAAGTAGGAAGAGCAATGTGTGCCCCTCCCAT
CGCAGGACAAATTAACTGTACAACAAAAATTACAGGGCTGTTATTAACAAGAGATGGTGGGAATAGCAAT
GAGACCAAAGAGACTGAAATCTTTAGACCTGGAGGAGGAGATATGAGGGACAATTGGAGAAGTGAATTAT
ACAAATATAAAGTAGTAAAAATTGAACCATTAGGAGTAGCACCCACCGAGGCAAGGAGAAGAGTGGTGCA
ACGAGAAAAGAGCAGTGGGACTAGGAGCTATGTTCCTTGGGTTCTTGGGAGCAGCAGAAGCACT
<U-343c3;PRT/1;HIV-1>
SAASLWVTVYYGVPVWKDANTTLFCASDAKAYDTEVHNVWATHACVPTDPNPQEVVLENVTENENMWKNN
MVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCTELMLNTTTNSTTTNSTSSPPTSSGLTNCSFNIATDLR
DKVQKEYALFSTLDVVSIGNNSSRLISCNTSILTQACPKVSFEPIPIHYCAPAGFAILKCNNKTFNGKGL
CNNVSTIQCTHGIKPVVSTQLLLNGSLAEKDIVIRSDNFSNNAKTIIVQLKKPVYINCTRPNNNTRKGIH
IAPGRAFYTTGQIIGDIRKAYCEISGKSWNNTLEQIATKLREQFGSNKTIVFNQSSGGDPEIVMHSFNCR
GEFFYCNSTQLFNSTWPGNGPSNNTTGNGTDTVIILPCRIKQIINMWQEVGRAMCAPPIAGQINCTTKIT
GLLLTRDGGNSNETKETEIFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTEARRRVVQREKS
<U-344c1;DNA;HIV-1>
AGAAAGAGCAGAGACAGTGGCAATGAGAGCGAAGGAGACCAGGAAGAATTGTCAGCACTCGTGGGGATGG
GGAACCATGCTCCTGTGGAGATGGGGCATCATGCTCCTTGGGATGTTAATGATCTGTAGTGCTAAAGAAA
ATTTGTGGGTCACAGTCTATTATGGGGTACCTGTGTGGAAAGAAGCATCCACCACTCTATTTTGTGCATC
AGATGCTAAAGCATATGATACAGAGGTACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCC
AGCCCACAAGAAGTAGTATTGGGAAATGTGACAGAATGTTTTAACATGTGGAATAACAACATGGTAGAAC
AGATGCATGAGGATATAATCAGTTATGGGACCAAAGTCTAAAAACCCTGTGTAAAATTAACCCCACTCTG
TGTTACCTTAAGTTGCAGTGACGTTAATATTACAATATTATATCAATAACTATTGCTAAAAAATAATAGT
TTAAGAATGGAAACAGGAGACATAAAAAACTGCTCTTTCAATATCACCACAAACATAAGAGATAAGATGC
AAACAGAATATGCACTTTTTTATAAATTTGATGTAGTGCCAATATATGATAGCAATGATGATAGCAATAT
TACTAGAAATGATAGTTATAGGATAATAAGTTGTAATACCTCAGTCATTACACAGGCCTGTCCAAAGGTA
ACCTTTGAGCCAATTCCCATACATTATTGTGCCCCGGCTGGTTTTGCGATTCTAAAGTGTAACAATAAGA
CATTCAATGGAAAAGGACCATGTACAAATGTCAGCACAGTACAATGTACACATGGAATTAGGCCAGTAGT
GTCAACTCAACTACTGTTAAATGGCAGTCTAGCAGAAAAGGAGATAGTGATTAGATCTGACAATTTCTCG
GACAATGCTAAAACTATAATAGTACAGTTAAATGGAACTGTTCAAATTAATTGTTCAAGACCCGGCAACA
ATACAAGAAAAAAGTATACATATAGGACCAGGAGTGCATTTTATGCAACAGGAGACATAATAGGAGATAT
AAGAAAAGCACATTGTAACATTAGTAAAACAGACTGGAATAACACTTTAGGAAAGATAGCAAAAAAATTA
AGAGAACAATTTGGGGAAAATAAAACAATAGAGTTTGAGAAATCCACAGGAGGGGACCCAGAAGTTATGA
TGCATACTTTTAATTGTGGAGGGGAATTTTTCTACTGTAATTCAACACCGCTGTTTAATGGGTAGTCTTT
TAATAATACTTGGACACCTTTGAATAGTAGTGCTAAAGGGCCAAATGACACTCTCATACTCCAATGTAGA
ATAAAACAAATCATAAACATGTGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATCAGAGGATACA
TTAATTGTTCATCAAATATTACAGGGCTGCTATTGACAAGGATGGTGGTAATTAATACTGGTAATGATAG
CAATACCGAGACCTTCAGACCTACAGGAGGAAATATGAAGGACAATTGGAGGAGTGAATTATATAAATAT
AAAGTAGTACAAATTGAACCATTAGGAGTAGCACCCACCAGGGCAAAAAGAAGAGTGGTGCAGAGAGAAA
AAAGAGCAGCGCTGGGGGCTATGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-344c1;PRT/1;HIV-1>
SAKENLWVTVYYGVPVWKEASTTLFCASDAKAYDTEVHNVWATHACVPTDPSPQEVVLGNVTECFNMWNN
NMVEQMHEDIISLWDQSLKPCVKLTPLCVTLSCSDVNITNIINNTIAKNNSLRMETGDIKNCSFNITTNI
RDKMQTEYALFYKFDVVPIYDSNDDSNITRNDSYRIISCNTSVITQACPKVTFEPIPIHYCAPAGFAILK
CNNKTFNGKGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEKEIVIRSDNFSDNAKTIIVQLNGTVQINCS
RPGNNTRKSIHIGPGSAFYATGDIIGDIRKAHCNISKTDWNNTLGKIAKKLREQFGENKTIEFEKSTGGD
PEVMMHTFNCGGEFFYCNSTPLFNGSTFNNTWTPLNSSAKGPNDTLILQCRIKQIINMWQEVGKAMYAPP
IRGYINCSSNITGLLLTRDGGNNTGNDSNTETFRPTGGNMKDNWRSELYKYKVVQIEPLGVAPTRAKRRV
VQREKR
<U-363c2;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGAGATCAGGAAGAACTATCAGCACTTGTGGAGATG
GGGCATCATGCTCTTTGGGATATTAATGATCTGTAGTGCTGAAGAAAAGTGGGTCACAGTCTATTATGGG
GTACCTGTGTGGAAAGAAGCAAAGACCACTCTATTTTGTGCATCAGATGCTAAAGCATATGATACAGAGG
CACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTAGTATTGGAGAA
TGTGACAGAAAATTTTAACATGTGGAAAAATGACATGGTAGAGCAGATGCATGAGGATGTAATCAGTTTA
TGGGATCAAAGCCTAAAGCCATGTGTAGAATTAACGCCACTCTGTGTTACTCTAAATTGCACTAATCTAA
ATTGCACTAACAACACTAGTAGCGAAATAAAAAACTGTTCTTTCTATGTCACCACAAGCATGGAAGGTAA
GGTGAAAAACATGCAACGTTTTATAGCCTTGATATAAGTACGAACAACAGAGAGTAATATCAGCTATAGG
TTGATAAGTTGTAACACCTCAGTCATTACACAGGCCTGTCCAAAAATATCCTTTGAACCAATTCCCATAC
ATTATTGTGCCCCGGCTGGTTTTGCGATCCTAAAGTGTAACAATAAGACATTCAATGGAACAGGACCATG
TACAAATGTCAGCACAGTGCAATGTACACATGGAATTAAGCCAGTAGTATCAACTCAACTACTGTTAAAT
GGCAGTCTAGCAGAGGAAGAGGTAGTAATTAGATCTGAAAATTTCATGAGAAATGATAAAATCATAATAG
TACAGCTAAATGAATCTATAGAAATTAATTGTACAAGACCCAACTATAATACAAGAAAAGGTTTCCATAT
AGGACCAGGGAGAGCAATTTATACAGGACAAATAATAGGAGATATCAGACAAGCACATTGTAACATTAGT
GGAATAAAATGGAAGAAGGCTTTAAAACAGATAGTTGGAAAATTAAGAGAACAATTTGGGAATAAAACAA
TAGTATTTAATCAGTCCTCAGGAGGGGACCTAGAAATTGAAACACACAGTTTTAATTGTGGAGGGGAATT
TTTCTACTGCAATACAACACAACTGTTTAATAATACTTGGCCGTCAAATAATACTGACGGAGATATTAAC
GAAAACATCACACTCACACTCCCATGCAGAATAAAACAAATTATAAACATGTGGCAGAAAGTAGGAAAAG
CCATGTATGCCCCTCCCATCAAAGGACAAATTAGATGTTCATCAAATATTACAGGGCTGCTACTAATGAG
AGATGGTGGTAACGACACCACCAAGGCAAACGACACCGAGGTCTTCAGACCTGGAGGAGGGGAGATGAGG
GACAATTGGAGAAGTGAATTATAAATATATAAAGTAGTAAAAATTGAACCATTAGGAATAGCACCCACCA
AGGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAAGAGGAGTAGGATTAGGAGCTATGTTCCTTGGGTTCTT
GGGAGCAGCAGGAAGCACT
<U-363c2;PRT/1;HIV-1>
SAEEKWVTVYYGVPVWKEAKTTLFCASDAKAYDTEAHNVWATHACVPTDPNPQEVVLENVTENFNMWKND
MVEQMHEDVISLWDQSLKPCVELTPLCVTLNCTNLNCTNNTSSEIKNCSFYVTTSMEGKVKKHATFYSLD
IVRTTESNISYRLISCNTSVITQACPKISFEPIPIHYCAPAGFAILKCNNKTFNGTGPCTNVSTVQCTHG
IKPVVSTQLLLNGSLAEEEVVIRSENFMRNDKIIIVQLNESIEINCTRPNYNTRKGFHIGPGRAIYTGQI
IGDIRQAHCNISGIKWKKALKQIVGKLREQFGNKTIVFNQSSGGDLEIETHSFNCGGEFFYCNTTQLFNN
TWPSNNTDGDINENITLTLPCRIKQIINMWQKVGKAMYAPPIKGQIRCSSNITGLLLMRDGGNDTTKAND
TEVFRPGGGEMRDNWRSELYKYKVVKIKPLGIAPTKAKRRVVQREKR
<U-033c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGAGATCAAGAGGAGTTATCAGCTCTTGTTGAAAGG
GGGCATCTTGCTCCTTGGGATATTGATGATCTGTAGTGCTACAGACAACTTGTGGGTCACAGTATATTAT
GGGGTACCTGTATGGAAAGAAGCAACCACCACTCTATTTTGTGCATCAGATGCTAAAGCCCATAATACAG
AGGTACACAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCTGACCCACAAGAAGTAGTATTGGA
AAATGTGACAGAAAATTTTAACATGTGGAAAAAATGACATGGTAGAACGATGCATGAGGATATAATCAGT
TTATGGATCAAAGCCTAAAGCCATGTGTAAAAATTAACCCCACTTTGTGTTACTTTAAATTGCACTAATG
CTAAAATGAACAATACTGCTGATACCAATGCTACTAATACTGTTAATATCAGCAAGGAAGAAATGGAAGA
AATAAAAAACTGCTCTTTCAATGTCACCACAAGCTTAAGAGATAAGATGCAGAGCCAATATGCATTGTTT
TATAAACTTGATATAGTACCAATAGATAATAGTAGTAGTATAGATAATAGTAGTAATACATGTAATAGTA
ATAGTACACATAATAATAGTAGTACATGTAATAATTATGCTAATTATAGATTGATAAGTTGTGACACCTC
AGTCATTACACAGGCCTGTCCAAAGGTATCCTTTGAGCCAATTCCCATACATTATTGTGCCCCGGCTGGT
TTTGCGATTCTAAAGTGTAATAATAAGACGTTCAATGGATCAGGACCATGTAAAAATGTCAGCACAGTAC
AATGTACACATGGAATCAGGCCAGTAGTATCAACTCAACTGCTGTTAAATGGCAGTCTAGCAGAAGAAGG
GGTAGTTATTAGATCTGAGAATTTCACAAACAATGCTAAAACCATAATAGTACAGATACATGAACCTATA
GAAATTAATTGTACAAGACCCAACAACAATACAAGAAAAAGTATAACTATAGGACCAGGAAGAGCGTTTT
ATGCAACAGGAGACATAATAGGAGATATAAGACAAGCACATTGTAACCTTAGTAAAGCAAGATGGAATGA
TACTTTAAAACAGATAGTTACAAAATTAAGAGAACAGTTTAGAAATAAAACAATAAATTTTACTCAATCC
TCAGGAGGGGACCCAGAAATTGTGATGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGTAATACAA
CACAACTGTTTAATAGTACTTGGTTGTCTAATAGTACTTGGAATGATACTGAAAGGTCAAATGGCACTGA
AACTATTACACTCCCATGCAGAATAAAGCAAGTTATAAACAGGTGGCAGGAAGTAGGAAAAGCAATGTAT
GCCCCTCCCATCAGTGGAATAATTAGATGTTCATCAAATATTACAGGGCTGCTATTAACAAGAGATGGTG
GTAATAGTAATGACACTCCGACTGATACTGAGATCTTCAGACCTGGAGGAGGAGATATGAGGGACAATTG
GAGAAGCGAATTATATAAATATAAAGTAGTAAAAATTGAACCATTAGGAATAGCACCCACCAAGGCAAAG
AGAAGAGTGGTGCAGAGAGAAAAAAGAGCAGCGGGAATAGGAGCTCTGTTCCTTGGGTTCTTGGGAGCAG
CAGGAAGCACT
<U-033c1;PRT/1;HIV-1>
SATDNLWVTVYYGVPVWKEATTTLFCASDAKAHNTEVHNVWATHACVPTDPDPQEVVLENVTENFNMWKN
DMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCTNAKMNNTADTNATNTVNISKEEMEEIKNCSFNVTTS
LRDKMQSQYALFYKLDIVPIDNSSSIDNSSNTCNSNSTHNNSSTCNNYANYRLISCDTSVITQACPKVSF
EPIPIHYCAPAGFAILKCNNKTFNGSGPCKNVSTVQCTHGIRPVVSTQLLLNGSLAEEGVVIRSENFTNN
AKTIIVQIHEPIEINCTRPNNNTRKSITIGPGRAFYATGDIIGDIRQAHCNLSKARWNDTLKQIVTKLRE
QFRNKTINFTQSSGGDPEIVMHSFNCGGEFFYCNTTQLFNSTWLSNSTWNDTERSNGTETITLPCRIKQV
INRWQEVGKAMYAPPISGIIRCSSNITGLLLTRDGGNSNDTPTDTEIFRPGGGDMRDNWRS&LYKYKVVK
IEPLGIAPTKAKRRVVQREKR
<U-060c4;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGGATCAGGAAGAATTGTCAGCGCTGGTGGAGATG
GGGCATCATGCTCCTTGGGATGTTGATGATCTGTAAAGCTGCAGACCAATTGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGGAAGGAAGCAACCACCACTTTATTTTGTGCATCAGATGCTAAAGCATATAAGACAG
AGGTACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAATCCACAAGAAATAGACTTGGC
AAATGTGACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGATATAATCAGT
TTATGGGATCAAAGCCTAAAGCCATGTGTAAAACTAACCCCACTCTGTGTTACTTTAAATTGTACTGATG
ACTTAGAAAATTGTAAAAATACCACTAATAATAATGCCGCTAATAATAATAATACCTGCGACATGCCAGG
AGAAATAAAGAACTGCTCTTTCAATATCACCGCAGGTATAAGAGATAAGATGCAGAAAGAATATGCACTT
TTTAATACACTTGATGTAGTACCAATAGGTGATGAGAATGATAATACCAGTTATAGGTTAATAAGTTGTA
ATACCTCAGTCATTACACAGGCCTGTCCAAAGGTATCCTTTGAGCCAATTCCCATACATTATTGTGCCCC
GGCTGGTTTTGCGATTCTAAAGTGTAAAGATAAGAAATTCAATGGGACAGGACAGTGTAAAAATGTCAGC
ACAGTACAATGTACACATGGAATTAAGCCAGTAGTATCAACTCAATTACTGTTAAATGGCAGTCTAGCAG
AAGAAGAGGTAGTAATTAGGTCTGAAAATTTCACAAACAATGCTAAAACCATAATAGTACAGCTGAAAGA
ACCTGTACAAATTAATTGTACAAGGCCCAACAACAATACAAGAAAAAGCATACATATAGGACCAGGGAGA
GCATTTTATGCAACAGGACAAATAATAGGAGATATAAGACAAGCACATTGTAACATTAGTAGTATAAAAT
GGAATAACACTTTAAAACAGATAGTTAAAAAATTAAGAGAACAATTTAATAAAACAATAATCTTTAATCA
ATCCTCAGGAGGGGACCCAGAAATTGTAATGCACATTTTTAATTGTAGAGGGGAATTTTTCTACTGTAAT
ACAACACAACTGTTTAATAGCACTTGGAATATTACTGAAGGGTCAAATGACAATATTACAGGCAGGTCAA
ATGACACTATCACGCTCCCATGCAAGATAAGACAAATTGTAAACATGTGGCAGGAAGTAGGAAAAGCAAT
GTATGCTCCTCCCATCAGAGGACAAATTAACTGTACATCAAATATTACAGGGCTGCTGTTAACAAGAGAT
GGTGGTAAAAATATCAGCGAGTCCGAAACCTTCAGACCTGGAGGAGGAAATATGAAGGACAATTGGAGAA
GTGAATTATATAAATACAAAGTAGTACAAATTGAACCATTAGGAGTAGCACCCACCAAGGCAAAGAGAAG
AGTGGTGCAGAGAGAGAAAAAGCAGTGGGAATAGGAGCTCTGTTCCCTTGGGTTCTTGGGAGCAGCAGGA
AGCACT
<U-060c4;PRT/1;HIV-1>
KAADQLWVTVYYGVPVWKEATTTLFCASDAKAYKTEVHNVWATHACVPTDPNPQEIDLANVTENFNMWKN
NMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCTDDLENCKNTTNNNAANNNNTCDMPGEIKNCSFNITA
GIRDKMQKEYALFNTLDVVPIGDENDNTSYRLISCNTSVITQACPKVSFEPIPIHYCAPAGFAILKCKDK
KFNGTGQCKNVSTVQCTHGIKPVVSTQLLLNGSLAEEEVVIRSENFTNNAKTIIVQLKEPVQINCTRPNN
NTRKSIHIGPGRAFYATGQIIGDIRQAHCNISSIKWNNTLKQIVKKLREQFNKTIIFNQSSGGDPEIVMH
IFNCRGEFFYCNTTQLFNSTWNITEGSNDNITGRSNDTITLPCKIRQIVNMWQEVGKAMYAPPIRGQINC
TSNITGLLLTRDGGKNISESETFRPGGGNMKDNWRSELYKYKVVQIEPLGVAPTKAKRRVVQREKR
<U-062_2c5;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGGATCAGGAAGAATTATCAGCACTGGTGGAGATG
GGGGACCATGCTCCTTTGGTTATTGATGATCTGTAGTGCTGCAGAACAATTGTGGGTCACAGTTTACTAT
GGGGTACCTGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATCAGATGCCAAAGCATATGATCCAG
AGGCACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAATTAGTATTGGC
AAATGTGACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCAGGAGGATATAATCAGT
TTATGGGATCAAAGCCTAAAGCCATGTACAAAATTAACCCCACTCTGTGTTACTTTAAATTGTACTGATG
TGGAGTATAATAATGAAACTGCTTCCAATAATACTGCTTCCAATACTACTATTATTAATGGGGGAACAAT
AGAGGGAGATGGAATAAAAAACTGCTCTTTCAATATCACCACCAGCCTAAATAAGGTGCAGAAAGAAAAT
GCATATTTTTATAATCTTGATGTAGTACAAATAGATAATAGTGATAATACCAGCTATAGGTTAGTAAGTT
GTAACACCTCAGTCATTACACAGGCCTGTCCAAAGATATCTTTTGAGCCAATTCCCATACATTACTGTAC
CCCGGCTGGTTTTGCGATTCTAAAGTGTAATGATAAAAAGTTCAATGGAACAGGACCATGTAAAAATGTC
AGCACAGTACAATGTACACATGGAAATTAAGCCAGTAGTATCAACTCACTGTTGTTAAATGGCAGTCTAG
CAGAAGAAGAGGTAGTAATTAGATCAGAAAATTTCACAGATAATGCAAAAATCATAATAGTACAGCTGAA
TGAATCTATGGAAATTAATTGTGCAAGACCCAACAACAATACAAGAAAAGGTATACATATGGGACCAGGG
AAAGCATTTTATGCAACAGGAGCCATAATAGGAGATATACGAAGAGCACATTGCAACATTAGTCAAACAA
AGTGGAACAATGCCCTAAAACAGATAGCTATAAAGTTAAGAGAACAATTTGGGAATAAAACAATAGTCTT
TACAAACTCCTCAGGAGGGGACCCAGAAATTGTAATGCACAGTTTTAACTGTGGAGGGGAGTTTTTCTAC
TGTAATACATCACTCCTGTTTAATAGTATCTGGAATAGTACTACTTTGTCAAATAGCACTACAGGAGATG
GAAATATCACACTCCCATGCAGAATAAAACAAATTATAAATATGTGGCAGAAAGTAGGGAAAGCAATGTA
TGCCCCTCCCATCCAAGGACTAATTAAATGTACATCAAATATCACAGGGATGTTATTAATAAGAGATGGT
GGTAACATCAACTGCACTGAGACTAATACCACCAACTGCAATGAGACTGAGACCTTCAGACCTGTAGCAG
GAGATATGAGGGGACAATTGGAGAAGTGAATTATATAAATATAAAGTAGTAAAATTGAACCATTAGGAAT
AGCACCCACTAAGGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCAGCGGGACTAGGAGCTTTGTTC
CTTGGGTTTTTGGGAGCAGCAGGAAGCACT
<U-062_2c5;PRT/1;HIV-1>
SAAEQLWVTVYYGVPVWKEATTTLFCASDAKAYDPEAHNVWATHACVPTDPNPQENVLANVTENFNMWKN
NMVEQMQEDIISLWDQSLKPCTKLTPLCVTLNCTDVEYNNETASNNTASNTTIINGGTIEGDGIKNCSFN
ITTSLNKVQKENAYFYNLDVVQIDNSDNTSYRLVSCNTSVITQACPKISFEPIPIHYCTPAGFAILKCND
KKFNGTGPCKNVSTVQCTHGIKPVVSTQLLLNGSLAEEEVVIRSENFTDNAKIIIVQLNESMEINCARPN
NNTRKGIHMGPGKAFYATGAIIGDIRRAHCNISQTKWNNALKQIAIKLREQFGNKTIVFTNSSGGDPEIV
MHSFNCGGEFFYCNTSLLFNSIWNSTTLSNSTTGDGNITLPCRIKQIINMWQKVGKAMYAPPIQGLIKCT
SNITGMLLIRDGGNINCTEINTINCNETETFRPVGGDMRDNWRSELYKYKVVKIEPLGIAPTKAKRRVVQ
REKR
<U-071c11;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGAGATCAGGAGGAATTGTCAGCACTGGTGGTGGAA
ATGGGGCACCATGCTCCTTGGGATGTTGATGATCTGTAGTGCTAACGAGCAATTGTGGGTCACAGTCTAT
TATGGGGTACCTGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATCAGATGCTAAAGCATATGACA
CAGAGGCACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCTAACCCACAAGAAGTAGTATT
GGTAAATGTGACAGAAAATTTTAATATGTGGAAAAATAACATGGTAGAACAGACGCAGGAGGATATAATC
AGTTTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCACTCTGTGTTACTCTAAATTGCACTG
ATTGGACCCTACATTGCAATAATAATGATACTAATTGCACTACTTTAAAAAATGATACTAAAACCAATAA
TAATAGTAGTTTGAGAACAATGGAGGAGGAGAAGTAAAAAAACTGCTCTTTCAATGTCACCACAAGCCTA
AGAGATAAGGAGCGAAAAGAATATGCACTTTTTTATAAACTTGATGTAGTACCAATAGGTAATGATAATA
CAAGCTATACGCTGATAAATTGTAACACCTCAACCATTACACAGGCCTGTCCAAAGGTAACCTTTGAACC
AATTCCCATACATTATTGTACCCCGGCTGGTTTTGCGCTTCTAAAGTGTAATGATAAGAAGTTCAATGGA
ACAGGACAGTGTAAAAATGTCAGCACAGTACAATGTACACATGGAATTAGGCCAGTAGTATCAACTCAAT
TGCTGCTAAATGGCAGTCTATCAGAAGGAGAGGTAATGATTAGATCTGAAAATTTGACAAACAATGCTAA
AACCATAATAGTACAGCTGAATGAATCTATAGCAATTAATTGTACAAGACCCAACAACAATACAAGAAAA
AGTATAACTATAGGACCGGGGAGAGCATTTTTTACAACAGGAGAAATAACAGGAGATATAAGACAAGCAC
ATTGTAACCTTAGTGCAGTACAATGGAATAACACATTAAAACAGATAGTTGCAAAATTAAGGGAACAATT
TGGGAATAATACAATAAGCTTTAATAAATCCGCAGGAGGGGACCCAGAAATTGTAATGCACAGTTTTAAT
TGTGGAGGGGAATTTTTCTACTGTGATACAACACAGCTGTTTAATAGTACTTGGGATAATGACACAGACT
TAAGTATTAGAATGAGACTACAGAATCAAACAACAAAACTATCACACTCCCGTGCAGAATAAAAACAAAT
TATAAACACATGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATCAGAGGACAAATTAAATGTTCA
TCAAATATTACAGGGCTACTATTAACAAGAGATGGTGGTATGAACAATAGCGCCAACGAGACCTTCAGAC
CTGGAGGAGGAGATATGAGGGACAATTGGAGAAGTGAATTATATATAAATAAAGTAGTAAAAATTGAGCC
ATTAGGGGTAGCACCCACCAAGGCAAAGAGAAGAGCGGTGCAAAGAGAAAAAGAGCAGTTGGGAATAGGA
GCTGTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-071c11;PRT/1;HIV-1>
SANEQLWVTVYYGVPVWKEATTTLFCASDAKAYDTEAHNVWATHACVPTDPNPQEVVLVNVTENFNMWKN
MMVEQTQEDIISLWDQSLKPCVKLTPLCVTLNCTDWTLHCNNNDTNCTTLKNDTKTNNNSSLRTMEGGEV
KNCSFNVTTSLRDKERKEYALFYKLDVVPIGNDNTSYTLINCNTSTITQACPKVTFEPIPIHYCTPAGFA
LLKCNDKKFNGTGQCKNVSTVQCTHGIRPVVSTQLLLNGSLSEGEVMIRSENFTNNAKTIIVQLNESIAI
NCTRPNNNTRKSITIGPGRAFFTTGEITGDIRQAHCNLSAVQWNNTLKQIVAKLREQFGNNTISFNKSAG
GDPEIVMHSFNCGGEFFYCDTTQLFNSTWDNDTDLSIKNETTESNNKTITLPCRIKQIINRWQEVGKAMY
APPIRGQIKCSSNITGLLLTRDGGMNNSANETFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKAKRRA
VQREKR
<U-104_3c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGATCAGGAAGAATTGCTTACGGAAATGGGGGCAC
CATGCTCCTTGGGATATTAATGATCTGTAGTGCTGCAGGAAATTTGTGGGTCACAGTCTATTATGGGGTG
CCTGTGTGGAAAGAAGCAACCACCACTCTATTCTGTGCATCAGATGCTAAAGCATATGCTACAGAGGCAC
ATAATGTTTGGCCCACACATGCCTGTGTACCCACAGACCCTAACCCACAAGAAGTAGTAATGGAAAATGT
GACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGAGATAATCAGTTTATGG
GATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCACTCTGTGTTACTCTAAATTGCACTGACTGTGTGA
CTTCAAATTGCACTAAGTTGAAGAATGTCACTAATAATGCTAATATTAGCAAGATGGAGATGGAGGAGGG
AGAAATGAAAAACTGCTCTTTTTAACATCACCTCAGGCATGAGAGATAAGATGAGAAAGAATATGCATTT
TTTTATAAACTTGATATAGTACCAATAAGTAATGATAATACTAGCTATAGATTGATAAGTTGTAATACCT
CAGTCATTACACAGGCATGTCCAAAAGTATCCTTTGAGCCAATTCCCATACATTATTGTGCCCCGGCTGG
TTTTGCGATTCTAAAATGTAATGATAAGAAGTTCAATGGAACAGGACCATGTAAAAATGTCAGCACAGTA
CAATGTACACATGGAATTAGGCCAGTAGTGTCAACTCAATTGCTGTTAAATGGCAGCCTAGCAGAAGAAG
AGGTAGTAATTAGATCTGAAAATTTAACGGACAATGGTAAAACCATAATAGTACAGCTGAACGAATCTGT
ACACATTAATTGTACAAGACCCAGCAACAATACCAGAAAAAGTATACATATAGGACCAGGGAAAGCATTT
TATGCAACAGGACAAATAATAGGAGATATAAGACAAGCACACTGTAACATTAGTGAAAAACAATGGAATA
AAACTTTAAGCCAGATAGTTAAAAAATTAAGAGAACAATTTAAAAATAAAACAATAGTCTTTAATCAATC
CTCAGGAGGGGACCCAGAAATTGTAATCACAGTTTTTAATTGTGGAGGAGAATTTTTCTACTGTAATTCA
ACACAACTATTTAATACTACTTGGAATTGGAATGATACTGAAGGGTCAAATAACACTGAAAGAAATGAAA
GAAATATTACACTCCCATGCAGAATAAAACAAATTGTAAACAGGTGGCAGGAAGTAGGAAAAGCAATGTA
TGCCCCTCCCATCAGCGGACCAATTAGCTGTTCATCAAATATTACAGGGCTGCTATTAACAAGAGATGGT
GGTCTCCCAAACAATACTGAGACCTTCAGACCAGAAGGAGGAAATATGAAGGACAATTGGAGAAGTGAAT
TATATAAATATAAAGTAGTAAAAAATTGAACATTAGGAATAGCACCCACCAAGGCAAAGAGAAGAGTGGT
GCAAAGAGAAAAAAGAGCAGTGACATTAGGAGCTATGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-104_3c1;PRT/1;HIV-1>
SAAGNLWVTVYYGVPVWKEATTTLFCASDAKAYATEAHNVWATHACVPTDPNPQEVVMENVTENFNMWKN
NMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCTDCVTSNCTKLKNVTNNANISKMEMEEGEMKNCSFNI
TSGMRDKMKKEYAFFYKLDIVPISNDNTSYRLISCNTSVITQACPKVSFEPIPIHYCAPAGFAILKCNDK
KGNGTGPCKNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSENLTDNGKTIIVQLNESVHINCTRPSN
NTRKSIHIGPGKAFYATGQIIGDIRQAHCNISEKQWNKTLSQIVKKLREQFKNKTIVFNQSSGGDPEIVM
HSFNCGGEFFYCNSTQLFNTTWNWNDTEGSNNTERNERNITLPCRIKQIVNRWQEVGKAMYAPPISGPIS
CSSNITGLLLTRDGGLPNNTETFRPEGGNMKDNWRSELYKYKVVKIEPLGIAPTKAKRRVVQREKR
<U-141c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGGATCAGGAAGAATTATCAGCACTGGTGGAAATG
GGGCACGATGCTCCTTGGAATGTTGATGATCTGTAGTGCTGCAGAACAATTGTGGGTTACAGTCTATTAT
GGGGTACCTGTGTGGAAGGAAGCAAAGACCACTCTATTCTGTGCATCAGATGCTAAAGCATATGAAACAG
AGGTACATAATGTTTGGGCCGCACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTAGTATTGGC
AAATGTGACAGAAAATTTTAATATGTGGGACAACAACAAGGTAGAACAGATGCAGGAGGATATAATCAGT
TTATGGGATGAAGGCCTAAAGCCATGTGTAAAATTAACCCCACTCTGTATTACTCTAAATTGCACTGACC
CCTGTGATGCTCAAAATAGCACTCGAAGTTGCACTTATTTGAATGATACGGTGGAAGAGGAGAGAGGACA
AATAAGAAATTGCTCTTTCAATATCTCCACAAAGCTAGAAAATAGAAGGCAGACAGGATATGCAGTTTTT
GATAAACTTGATTTAGTACCAGTAGATGGTGGTAATAATACTGTCAGATATAGGTTGATAAATTGTAACA
CCTCAGTCATTACACAAGCATGTCCAAAGGTATCCTTTGAACCAATTCCCATACATTATTGTACCCCAGC
TGGTTTTGCGATTCTAAAGTGTAATGATAAGAAGTTCAATGGAACAGGGCCATGCACAAATGTCAGCACA
GTACAATGCACACATGGAATTAGGCCAGTAGTGTCAACTCAACTGCTGTTAAATGGCAGTCTGGCAGAAG
AAGAGGTAGTAATTAGATCTAAAAATTTCACAGACAATACTAAAACTATAATAGTACAGCTGAATGAATC
TGTACAAATTAATTGTACAAGACCCAACAACAATACAAGACAGAGTACACCTATGGGACCAGGGAAAGCA
CTTTACACAACACAGATAATAGGAGACATAAGACAAGCACATTGTAACATTAGTACAAAAGATTGGAATG
ACACCGGAAAAAGATAGTTACAAAATTAGAAGAACAATTTGAAAATAAAACAATAAGCTTTTAATCAATC
CTCAGGAGGGGACCCAGAAATTGTAAAGCACAGTTTTAATTGTGGAGGGGAATTCTTCTACTGTGATACA
ACAAAACTATTTAATAGTACTTGGCCTGCAAGTATCAATTATACCACTGGAGTAAATATCACTGGAGTTA
TCACACTCCCATGTAGAATAAAACAAATTATAAACAGGTGGCAGGGGAGGAGGAAAGGCAATGTATCTCC
TCCCATCAGTGGACCAATTAGATGTTCATCAAATATTACAGGGCTGCTATTAACAAGAGATGGTGGTGAT
GACAATAATGGGGCTGAGACCTTTAGACCTGGAGGAGGAGATATGAGGGACAATTGGAGAAGTGAATTAT
ATAAATATAAAGTAGTAAAAATTGAACCATTAGGAGTAGCACCCACCAAGGCAAAGAGAAGAGTGGTGCA
GAGAGAAAAAAGAGCAGTGGGAACACTAGGAGCTATGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-141c1;PRT/1;HIV-1>
SAAEQLWVTVYYGVPVWKEAKTTLFCASDAKAYETEVHHVWAAHACVPTDPVPQEVVLANVTENFNMWDN
NKVEQMQEDIISLWDEGLKPCVKLTPLCITLNCTDPCDAQNSTRSCTYLNDTVEEERGQIRNCSFNISTK
LENRRQTGYAVFDKLDLVPVDGGNNTVRYRLINCNTSVITQACPKVSFEPIPIHYCTPAGFAILKCNDKK
FNGTGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSKNFTDNTKTIIVQLNESVQINCTRPNNN
TRQSTPMGPGKALYTTQIIGDIRQAHCNISTKDWNDTLKKIVTKLEEQFENKTISFNQSSGGDPEIVKHS
FNCGGEFFYCDTTKLFNSTWPASINYTTGVNITGVITLPCRIKQIINRWQGGGKAMYAPPISGPIRCSSN
ITGLLLTRDGGDDNNGAETFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKAKRRVVQREKR
<U-165c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAAAGTGAGGGAGACCAGGAGGAATTATTGGGACTTGTGGAGATG
GGGCACGATGCTCCTTGGGATGTTAATGATCTGTAGTGCTACAGAACAATTATGGGTCACAATCTATTAT
GGGGTACCTGTGTGGAAAGAAGCAGATACCACTCTATTTTGTGCATCAGATGCTAAAGCATATGATACAG
AGAAACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCTAACCCACAAGAAGTAGTAATGGC
AAATGTGACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCAGAAGGATATTATCAGT
CTATGGGATGAAAGCTTAAAACCATGTGTAAAATTAACCCCACTCTGTATCACTTTAAATTGCAATACTT
TAAATTGCACACATAACAATAATTGTAGTAGTTTGAGAGAAGAAATGACAAACTGCTCCTTCAATGCCAC
CTCAAAATTGAGAGATAAGGTTCGGAAACAATATGCAATTTTTTCTAAACTTGATGTGGTAAAACTAGAT
AGTAATAATAATGAAACAGAATATAGGTTGATAAATTGTAACACCTCAGTCGTTACACAGGCCTGTCCAA
AGGTATCATTTGAGCCAATTCCCATACATTATTGTGCCCCGGCTGGTTTTGCGATTCTAAAGTGTAACAA
TAAGACATTCGATGGAAAAGGACCATGTACAAATGTCAGCACAGTACAATGTACACATGGAATTAGGCCA
GTAGTGTCAACTCAACTGCTGTTAAATGGCAGTCTAGCAGAAGAAGGGATAGTAATTAGATCTGACAATA
TCTCAGACAATACTAAAACCATAATAGTACAGCTGAATGAATCTGTAGCAATTAATTGTTCAAGACCCCA
CAACAATACAAGAAAAAGTATACATATAGCACCAGGGAGAGCCTTTTATGCAACAGGAGACATAATAGGA
GATATAAGACAAGCACATTGTAACATTAGTAGAAAACAATGGAATAAAACTTTAGAACAGGTAGCTAAAA
AATTAAGAGAAAAATTTGTAAATAAAGCAATTATCTTTAAAAACTCCTCAGGAGGGGACCCAGAAATTGT
AATGCACAGTTTTAATTGTAGAGGGGAATTTTTCTACTGTAATACAACACCACTGTTTAATGGGACTTGG
AATGGTACTAATTTGAGTACTAATAAGGAGTCAAATGACACAATCATACTCCAATGTAGAATAAAACAAA
TTATAAACATGTGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATTGCAGGACAAATTAACTGTTC
ATCAAAAATTACAGGGCTACTATTAACAAGAGATGGTAGTAGCACAAATGGGACAAATGAGACTGAGATC
TTCAGACCTGGAGGAGGAGATATGAGGGACAATTGGAGAAGCGAATTATATAAATATAAAGTAGTAAGAG
TTGAACCAATAGGAATAGCACCCACCAAGGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCAGTGGG
AACGTTAGGAGCTATGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-165c1;PRT/1;HIV-1>
SATEQLWVTIYYGVPVWKEADTTLFCASDAKAYDTEKHNVWATHACVPTDPNPQEVVMANVTENFNMWKN
NMVEQMQKDIISLWDESLKPCVKLTPLCITLNCNTLNCTHNNNCSSLREEMTNCSFNATSKLRDKVRKQY
AIFSKLDVVKLDSNNNETEYRLINCNTSVVTQACPKVSFEPIPIHYCAPAGFAILKCNNKTFDGKGPCTN
VSTVQCTHGIRPVVSTQLLLNGSLAEEGIVIRSDNISDNTKTIIVQLNESVAINCSRPHNNTRKSIHIAP
GRAFYATGDIIGDIRQAHCNISRKQWNKTLEQVAKKLREKFVNKAIIFKNSSGGDPEIVMHSFNCRGEFF
YCNTTPLFNGTWNGTNLSTNKESNDTIILQCRIKQIINMWQEVGKAMYAPPIAGQINCSSKITGLLLTRD
GSSTNGTNETEIFRPGGGDMRDNWRSELYKYKVVRVEPIGIAPTKAKRRVVQREKR
<U-187c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGACGGGGATCAGGAAGAATTACTTATGGAGATGGGGCAC
CTTATTCCTGGGGATATTGATGATCTGTAAGGCTGCAGAAAACTTGTGGGTCACAGTCTATTATGGGGTA
CCTGTGTGGAAAGACGCAACCACCACTCTATTTTGTGCATCAGATGCTAAAGCTGTTGATACAGAAGTAC
ACAATGTGTGGGCCACACATGCCTGTGTACCCACAGACCCAAACCCACAAGAAGTAGTATTGTATAATGT
GACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGATATAATCAGTTTATGG
GATGAAAGTCTAAAGCCATGTGTAAAGCTAACCCCACTCTGTGTTACTTTGAATTGCACTGATGAATTGA
ATATCAATACTAATAATACCTGTAGTAATACCAGTAGTGGCACTAATAATACCAGTAATTGCACTAATGC
TGAGTCGACTATCATCAGTACCAGTAATAGTAGCAATACCAGAAATATCAGTGATAGTAGCAAGATAGAG
AAAGGAGAAATAAAAAACTGTACTTTCAATATCACCACAAGCATAAGAGATAAGGTGCAGAAAGAATATG
CACTGTTTTATAAACTTGATGTAGTACCAACAGGTAGTGACAATACTAGCTATAGGTTGATAAGTTGTAA
TACCTCAGTCATTACACAGGCCTGTCCAAAGGTAACCTTTGAGCCAATTCCTATACATTATTGTGCCCCG
GCTGGTTATGCGATTGTAAAGTGCAACAATAAGACATTCAGTGAAAAGGACCATGTAAAAAATGTCAGCA
CAGTACAATGCACACATGGGATTAAGCCAGTAGTATCAACTCAGTTGCTGTTAAATGGCAGTCTGGCAGA
AAAAGATATAGTAATTAGATCTGACAACTTCTCAAACAATGCTAAAACCATAATAGTGCAGCTGAACACA
TCTGTAGAAATTAATTGTACAAGACCCAGCAACAATACAAGAAAAAGTATTCATATAGGACCAGGGAGAG
CATTTTATGCAACAGATATAATAGGAGATATAAGACAAGCACATTGTAACATTAGTGAAGAAAATTGGTA
TAAAACTCTAAAGCAGGTAGCTATGAAATTAGGAGAACAGTTTCAGAATAAAAAAATAGTCTTTAATCAA
TCCTCAGGAGGGGACCCAGAAATTGTAATGCACAGTTTTAATTGTGGAGGGGAATTTTTCTTCTGTAGTA
CATCACAACTGTTTAATAGTACTTGGAATTATAGTACTTGGGATGAAATAGAAAATAAAACTCAAGGAAA
TGGCACACTCACACTCCCATGCAGAATAAAACAAATTGTAAACATGTGGCAGGAAGTAGGAAAAGCAATG
TATGCCCCTCCTATCAAAGGAAATATTACATGTTCATCAAAGATTACAGGGTTGCTATTAACAAGAGATG
GTGGTAAGACTAATATCAATGGCACCGAGATCTTCAGACCAGGAGGAGGAGATATGAGGGACAATTGGAG
AAGTGAACTATATAAATATAAAGTAGTAAAAATTGAACCATTAGGAATAGCACCCACCAAGGCAAAGAGA
AGAGTGGTGCAGAGAGAAAAAAGAGCAGTGGGAATAGGAGCTATGTTCCTTGGGTTCTTGGGAGGCAGCA
GGAAGCACT
<U-187c1;PRT/1;HIV-1>
KAAENLWVTVYYGVPVWKKATTTLFCASDAKAVDTEVHNVWATHACVPTDPNPQEVVLYNVTENFNMWKN
NMVEQMHEDIISLWDESLKPCVKLTPLCVTLNCTDELNINTNNTCSNTSSGTNNTSNCTNAESTIISTSN
SSNTRNISDSSKIEKGEIKNCTFNITTSIRDKVQKEYALFYKLDVVPTGSDNTSYRLISCNTSVITQACP
KVTFEPIPIHYCAPAGYAIVKCNNKTFSGKGPCKNVSTVQCTHGIKPVVSTQLLLNGSLAEKDIVIRSDN
FSNNAKTIIVQLNTSVEINCTRPSNNTRKSIHIGPGRAFYATDIIGDIRQAHCNISEENWYKTLKQVAMK
LGEQFQNKKIVFNQSSGGDPEIVMHSFNCGGEFFFCSTSQLFNSTWNYSTWDEIENKTQGNGTLTLPCRI
KQIVNMWQEVGKAMYAPPIKGNITCSSKITGLLLTRDGGKTNINGTEIFRPGGGDMRDNWRSELYKYKVV
KIEPLGIAPTKAKRRVVQREKR
<U-195c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGATGGGGATCAGGAGGAATTATCAGCACTTGTGGAGATG
GGGCACCATGCTCCTTGGGATGTTGATGATCTGTAAAATCACTACAGGAAAAACGTGGGTCACAGTCTAT
TATGGGGTACCTGTGTGGAAAGAAGCAACTACCACTCTATTTTGTGCATCAGATGCTAAAGCATATGATA
CAGAGGTACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAAAAATAGTAAT
GGTAAATGTGACAGAGGAATTTAACATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGATATAATC
AGTTTATGGGATCAGAGCCTAAAGCCATGTGTAAAATTAACCCCACTCTGCGTTACTTTAAATTGCAATG
ATACTACGGAGAGAAATTGCACTGGTCCCGATGGTAGAAAAATAAATTGCACTGAAGTGAAAAATTGCTC
TCTCAATATCACCACAAACATAAGAGATAAGGTGCAGAAAGAATATGCACTTTTTTATAGAACTGATGTG
GTGCCAATAGATAATAATAATACTAGTACCAGCAGTCATAGCTATAGGTTGATAAGTTGTAATACCTCAG
TCCTTACACAGACCTGTCCAAAAGTATCCTTTCAGCCAATTCCCATACATTATTGTGCCCCGGCTGGTTT
TGCGATTCTAAAATGTAACAATAGGACATTCAATGGAAAAGGAGAATGTGGTAATGTCAGCACAGTACAA
TGTACACATGGAATTAAGCCAGTAGTATCAACTCAGCTGCTGCTAAGTGGCAGTCTAGCAGAACAAGAGA
TAGTGCTTAGATCTGACAACTTCTCAGACAATGCTAAAACCATAATAGTACAGCTGACTAAACCTGTAGA
AATTAATTGTACACGACCCAACAACAATACAAGAAAAAGTATAGCTATAGGACCAGGGAGAGCATTTATT
GCAACAGGAGACATAATAGGAGATATAAGACAGGCACATTGTAACATTAGTAAAGTAGCATGGAATAACA
CTATAGAAGAGGTAGCAAGAAAATTAAGCAAACAATTTGGGAATAGATCAATAACCTTTAATCAATCCTC
AGGAGGGGACCCAGAAATTGTAATGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGTAATACAACA
GGACTATTTAGTAGTACTTGGAATGTTACTGATAATTGGAATGCTACTGAAGAGGCAAATACCACTAGGG
TAAATATCACACTCCCATGCAGAATAAGACAAATTGTAAACATGTGGCAGGAAGTAGGAAAAGCAATGTA
TGCCCCTCCCATCAGAGGACAAATTAGTTGCTCATCAAATATTACAGGACTGATATTAACAAGAGATGGT
GGTAACCAGAGCAACGAGACGACCCCTGAGATCTTTAGACCTGGAGGAGGAGATATGAGGGACAATTGGA
GAAGTGAATTATATAAATATAAAGTAGTAAAAATTGAACCTATAGGAATAGCACCCACCAAGGCAAAGAG
AAGAGTGGTGCAGAGAGAAAAAAGAGGGGTACTAGGAGCTATGTTCCTTGGGTTCTTGGGAGCAGCAGGA
AGCACT
<U-195c1;PRT/1;HIV-1>
KITTGKTWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHACVPTDPNPQKIVMVNVTEEFNMWK
NNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCNDTTERNCTGPDGRKINCTEVKNCSLNITTNIRDKV
QKEYALFYRTDVVPIDNNNTSTSSHSYRLISCNTSVLTQTCPKVSFQPIPIHYCAPAGFAILKCNNRTFN
GKGECGNVSTVQCTHGIKPVVSTQLLLSGSLAEQEIVLRSDNFSDNAKTIIVQLTKPVEINCTRPNNNTR
KSIAIGPGRAFIATGDIIGDIRQAHCNISKVAWNNTIEEVARKLSKQFGNRSITFNQSSGGDPEIVMHSF
NCGGEFFYCNTTGLFSSTWNVTDNWNATEEANTTRVNITLPCRIRQIVNMWQEVGKAMYAPPIRGQISCS
SNITGLILTRDGGNQSNETTPEIFRPGGGDNRDNWRSELYKYKVVKIEPIGIAPTKAKRRVVQREKR
<U-208_4c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGGATCAGGAAGAATTGTCACTCCTGGAGATGGGG
CACCATGCTCCTATGGAGATGGGGCACCATGCTCCTTGGGTTGTTAATGATGATCTGTAATGCTAAAGAA
GAAAAAACGTGGGTCACAGTATATTATGGGGTACCTGTGTGGAAAGAAGCGACCACCACTCTATTTTGTG
CATCAGATGCTAAAGCATATGACACAGAGGTACATAATGTTTGGGCCACACATGCCTGTGTACCTACAGA
CCCCGACCCACAGGAAATATTCTTGGAAAATGTGACAGAAAATTTTAACATGTGGAAAAATAACATGGTA
GAACAGATGCATGAGGATATAATCAGTTTGTGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCAC
TCTGTGTTACGTTAAATTGCACTAATGTGAGGATTACTAGCATAAATTGCACTGATGCGAGTAGTAATAG
CACTGGTGTGGAAAAAACTACTAGCACTAATGGGGGGAATGTTACTATTTGTAATACTACTGAGGAGATA
AAAAACTGCTCCTTCAACATCACCACCAACATGAAAGATAAGATACAGAAGACATATGCACTGTTTTATA
AACTTGATGTAGAACCAATAGATAAGGGGAATGAGAATAGCACCAGCTATAGGGTGATAAGTTGTAACAC
TTCAACCATTACACAGGCCTGTCCAAAGGTATCCTTTGAGCCAATTCCTATACATTATTGTGCCCCGGCT
GGTTTTGCGATTCTAAAATGTAGAGATAAAAGGTTTAATGGAACAGGACCATGTACAAATGTCAGCACAG
TACAATGTACACATGGAATTAAACCAGTAGTATCAACTCAACTGCTGTTAAATGGCAGTCTAGCAGAAGA
AGAGATAGTACTTAGATCTGAAAATTTCTCGAACAATGCTAAAAACATATTAATACAGCTAAAAGAACCT
GTAGAAATTAATTGTACAAGACCCAACAACAATACAAGAAAAGGTATACATATAGGACCAGGAAGAGCAT
TTTATGGAACAGATATAATAGGAGATATAAGACAAGCACATTGTAACATTAGCAGAGAAAAATGGAATAG
CACTTTAAGTCAGATAGTTGATAAATTAAGAGAACAATATGGGAAAAATAAAACAATAATCTTTGATCAA
CCATCAGGAGGGGACCCAGAAATTGTAACGCACAGTTTTAATTGTGGAGGAGAATTTTTCTACTGTAATT
CAACACAACTGTTTAATAGCACTTGGTATGATAATAGTACTTGGAATGAGAATAAAAATCACACTAAAAA
TGACACAATCACGCTCCCATGCAGAATAAAGCAATTTATAAACATGTGGCAGGAAGTAGGGAAAGCAATG
TATGCCCCTCCCATCAGAGGACAAATTAAATGCTCATCAAATATTACAGGGCTAATAATAACAAGAGATG
GGGGGAACAACAACAGCGAGACCTTCAACAACGAGACCTTCAGACCTGGAGGAGGAAATATGAAGGACAA
TTGGAGAAGTGAATTATATAAATATAAAGTAGTAAGAATTGAGCATTAGGAGTAGCACCCACCAAGGGCA
AAGAGGAGAGTGGTGCAGAGAGAAAAAAGAGCAGTGGGAATAGGAGCTGTGTTCCTTGGGTTCTTGGGAG
CAGCAGGAAGCACT
<U-208_4c1;PRT/1;HIV-1>
NSKEEKTWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHACVPTDPDPQEIFLENVTENFNMWK
NNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCTNVRITSINCTDASSNSTGVEKTTSTNGGNVTICNT
TEEIKNCSFNITTNMKDKIQKTYALFYKLKVEPIDKGNENSTSYRVISCNTSTITQACPKVSFEPIPIHY
CAPAGFAILKCRDKRFNGTGPCTNVSTVQCTHGIKPVVSTQLLLNGSLAEEEIVLRSENFSNNAKNILIQ
LKEPVEINCTRPNNNTRKGIHIGPGRAFYGTDIIGDIRQAHCNISREKWNSTLSQIVDKLREQYGKNKTI
IFDQPSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWYDNSTWNENKNHTKNDTITLPCRIKQFINMWQEV
GKAMYAPPIRGQIKCSSNITGLIITRDGGNNNSETFNNETFRPGGGNMKDNWRSELYKYKVVRIEPLGVA
PTRAKRRVVQREKR
<U-210c2;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGGACCAAGACGAATTATCAGCACTTATGGAGATG
GGGCATCATGCTCCTGGGGATATTGATGATCTGTAGTGCTACAGAACAATGGTGGGTCACAGTCTATTAT
GGAGTACCTGTGTGGAGAGATGCAAATACCACTCTATTTTGTGCATCAGATTCTAAAGCATATGCTACAG
AGGTACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAATAAACTTGGA
AAATGTAACAGAAGAGTTTAACATATGGAAAAATAACATGGTAGAACAAATGCATGAGGATATAATCAGT
TTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCACTCTGTGTTACTTTAAATTGCACTGATT
ACAATGGTACTCATACCAATACTACTAATACCACTAGTATTTATGGGGAAAAGATGGAAATAGGAGAAGT
AAAGAAATGCTCTTTCAATGCTACCACAATCATAAGAGATAAGGTGGACAAAGAAGAAGCACTTTTTTAT
AAACTTGATATAGTACCAATAGATGGTAATAATGAGACTAACATAGTTAATAATGGGACTAATAATACTA
GTACCAACTATACCAGCTATAGGCTAATAAATTGTAACACCTCAGTCATTACACAGGCCTGTCCAGAGGT
ATCCTTTGAGCCAATTCCCATACATTATTGTGCCCCGGCTGGTTTTGCGATTCTAAAGTGTAAAGAGAAG
GCGTTCAATGGAAGTGGGCCATGTAAAAATGTCAGCTCAGTACAATGTACACATGGAATTAAGCCAGTAG
TATCAACTCAATTGCCGTTAAATGGCAGTCTAGCAGAAGAAGAAGTAGTAATTAGATCTGAAAATTTCAC
AAACAATGCTAAAACCATAATAGTACAGCTGAAAGAAGCTGTAAACATTAGTTGTATAAGGCCCAACAAC
AATACAAGAAAAAGTATACCTATAGGACCAGGGAGAGCATTTTATGCAACAGGAGACATAATAGGAGATA
TAGGACAAGCACATTGTAACCTTAGTAGAACAAATTGGAATAAAACTTTACAACAGATAGCTACAAAATT
AGGAGAAAAGTTTAATAAAACAACAATAATCTTTAATCAATCCTCAGGAGGGGACCCAGAAATTGTAATG
CACAGTTTTATTTGTGGAGGGGAATTTTTCTACTGTAATACAACACAACTGTTTAATAGTACTTGGAACT
GTACTGAGAATGGGAATTGTACACTGGTTACCGGTACTTGGCCTGACAGGCCAAATAGAACTGGAGAAAA
TGACACAATCACACTCCCATGCAGAATAAAACAAATCATAAACCTGTGGCAGGAAGTAGGAAAAGCAATG
TATGCCTCTCCCATCCAGGGACTAATTAATTGTACATCAAATATTACAGGGCTGCTATTAACAAGAGATG
GTGGTACCCATAGTAGACAGAATGAGACCTTCAGACCTGAAGGAGGAAATATGAAAGACAATTGGAGAAG
TGAATTATATAAATATAAAGTAGTAAGAATTGAACCATTAGGAGTAGCACCCACCAAGGCAAAGAGAAGA
GTGGTGCAGAGAGAAAAAAGCGCAGTGGGATTGGGAGCTATGATCCTTGGGTTCTTGGGAGCAGCAGGAA
GCACT
<U-210c2;PRT/1;HIV-1>
SATEQWWVTVYYGVPVWRDANTTLFCASDSKAYATEVHNVWATHACVPTDPNPQEINLENVTEEFNIWKN
NMVEQMHHDIISLWDQSLKPCVKLTPLCVTLNCTDYNGTHTNTTNTTSIYGEKMEIGEVKKCSFNATTII
RDKVDKEEALFYKLDIVPIDGNNFTNIVNNGTNNTSTNYTSYRLINCNTSVITQACPEVSFEPIPIHYCA
PAGFAILKCKEKAFNGSGPCKNVSSVQCTHGIKPVVSTQLPLNGSLAEEEVVIRSENFTNNAKTIIVQLK
EAVNISCIRPNNNTRKSIPIGPGRAFYATGDIIGDIGQAHCNLSRTNWNKTLQQIATKLGEKFNKTTIIF
NQSSGGDPEIVMHSFICGGEFFYCNTTQLFNSTWNCTENGNCTLVTGTWPDRPNRTGENETITLPCRIKQ
IINLWQEVGKAMYASPIQGLINCTSNITGLLLTRDGGTHSRQNETFRPEGGNMKDNWRSELYKYKVVRIE
PLGVAPTKAKRRVVQREKR
<U-215_2c1;DNA;HIV-1>
AGAAAGAGCAAAACAGTGGCAATGAAAGTGAAGGGGACCAGGATGAATTGTCAGCGCTGGTGGTGGACAT
GGGGCACGATGCTCCTTGGGATGTTGATGATCTGTAGTGCTGCAGAAAAGTTGTGGGTCACAGTCTATTA
TGGGGTACCTGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATCAGATGCTAAAGCATATAAGACA
GAAAAGCATAATGTCTGGGCCACACATGCCTGTGTACCCACAAACCCCAACCCACAAGAAGTAGTAATGG
AAAATGTAACAGAATATTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCAGGAGGATATAATCAG
TTTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTATCCCCACTCTGTGTAACTTTAACTTGTGTGAAT
ATTACTAACTGTAAGAATAATACTAACTGTAATAATGATACTAACAGTAAGAATGATACTCTTAAGGAGG
AGATAGGGGAAATAAAAAACTGCTCTTTCAACGTCACCACAGCCATAAGAGATAAGGTGCAGAAAGAATA
TGCATTATTTCATAAACTTGATGTAGTACAAATAGATAATGATAATACTAGTAGTAATACTTCTAAGCCT
TATAGGTTGATAAGTTGTAACACCTCAGTCATTACACAGGCCTGTCCAAAGGTAACCTTTGAGCCAATTC
CCATACATTATTGTGCCTCGGCTGGTTTTGCGATTCTAAAGTGTAACAATAAGACTTTCAATGGAACAGG
ACCATGTACAAATGTCAGCACAGTACAATGTACACATGGAATTAGGCCAGTAGTATCAACTCAACTGTTG
TAAAATGACAGCCTAGCAGAAAAAGAGGCAATAGTTAGATCTGAAAATTTCACAAACAACGCTAAAATCA
TAATAGTACAGCTAAATGAATCTGTAGAGATTAATTGTACAAGACCCAACAACAATACAAGAAGAAGTAT
ACCTATAGGACCAGGGAAAGCATTTTTTACATCAGAAATAATAGGAGATATAAGAAAAGCACACTGTAAC
ATTAGTGGAACAAAGTGGAATGCCACTTTGCATAAAATAGCTATAAAATTAAGAGAACAATATGGAAATA
AAACAATAGTCTTTAATCAACCTTCAGGAGGGGACCCAGAAGTTGTAATGCACAGTTTTAACTGTGGAGG
GGAATTTTTCTACTGTGATACAACACAACTGTTTAATAGTACTTGGTTTAATAGTACTTGGCCAAATATC
ACACTTGAAGAAAATATCACACTCCCATGCAAAATAAAACAATTTATAAACATGTGGCAGGAAGTAGGAA
AAGCAATGTATGCCCCTCCCATCAGAGGACAAATTAACTGTTCATCACAGATTACAGGGCTGCTATTAAC
AAGAGATGGTGGTCAGGGTAACAATACTAACAACGACACTGAGATTTTCAGACCAGGGGGAGGAGATATG
AGGGACAATTGGAGAAGTGAATTATACAAATATAAAGTAGTAAGAATTGAGCCATTGGGAGTAGCACCCA
CCAAGGCAATGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCAATAGGACTAGGAGCTTTTTTCCTTGGGTT
CTTGGGAGCAGCAGGAAGCACT
<U-215_2c1;PRT/1;HIV-1>
SAAEKLWVTVYYGVPVWKEATTTLGCASDAKAYKTEKHNVWATHACVPTHPNPQEVVMENVTEYENMWKN
NMVEQMQEDIISLWDQSLKPCVKLTPLCVTLTCVNITNCKNNTNCNNDTNSKNDTLKEEIGEIKNCSFNV
TTAIRDKVQKEYALFHKLKVVQIDNDNTSSNTSKPYRLISCNTSVITQACPKVTFEPIPIHYCASAGFAI
LKCNNKTFNGTGPCTNVSTVQCTHGIRPVVSTQLLLNDSLAEKEAIVRSENFTNNAKIIIVQLNESVEIN
CTRPNNNTRRSIPIGPGKAFFTSEIIGDIRKAHCNISGTKWNATLHKIAIKLREQYGNKTIVFNQPSGGD
PEVVMHSFNCGGEFFYCDTTQLFNSTWFNSTWPNITLEENITLPCKIKQFINMWQEVGKAMYAPPIRGQI
NCSSQITGLLLTRDGGQGNNTNNDTEIFRPGGGDMRDNWRSELYKYKVVRIEPLGVAPTKAMRRVVQREK
R
<U-234c10;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGATGGGGATCAGGAAGAGTTATCAGCACTTGTGGAAAGG
GGGCACCTTGCTCCTTGGAATATTGATGATCTGTAGTGCTGCAGAACAATTGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGGAAAGATGCAACCACCACTTTATTTTGTGCATCAGATGCTAAAGCATATGATACAG
AGGTACACAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTAGTAATGGG
AAATGTGACAGAATATTTTAACATGTGGACAAATAACATGGTAGAACAGATGCATGAGGATGTAATCAGT
TTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCACTCTGTGTTACTTTAAATTGCACTAATT
TGGTGAATACTACCTGTAATGGGACTACTAACAATAATACTACCTGTACTGGGACTGCTAACAATGATAC
TAATACCAATAGTACTAGGTGGGTGTATCAAGCGATGGCAGGAGAAATAAAAAACTGCTCTTTCAATATC
ACCACAAACATAAGAGATAAGATAAAAAAAGAATATGCACTTTTTAATAGACTTGATATAGTACCAATAG
ATGATGAGAATAAGAATACTGGCAATACTAGTAGCTATAGGTTGATAAGTTGTAACACCTCAGTCATTAC
ACAGGCCTGTCCAAAGGTAACCTTTGAACCAATTCCCATACATTATTGTGCCCCGGCTGGTTTTGCGATT
CTCAAGTGTAATGATAAGAAGTTCAATGGAACAGGACCATGTACAAATGTCAGCACAGTACAATGTACAC
ATGGAATTAGGCCAGTAGTATCAACTCAACTACTATTAAATGGCAGTCTAGCAGAAGAAGAGACAGTAAT
TAGATCTAGCAATTTCTCGAACAATGCTAAAATCATAATAGTACAGCTGAATGAAACTGTACGAATTAAT
TGTACAAGACCCAACAACAATACAAGAAGAAGTATACATATAGGACCAGGGAGAGCATTTTATGCAACAG
GAGACATAATAGGAGATATAAGACAAGCACATTGTAACATTAGTGGAGAAGAATGGAGGAGAACTTTAAA
ACGGATAACTATAAAATTAGGAGAACAATTTAATAAAACAAAAATAAGCTATAACCAATCCTCAGGAGGG
GACCCAGAAATTGTAAGGCACAGTTTTAATTGTCAAGGGGAATTTTTCTACTGTGATACATCAGGACTGT
TTAATAGTACTTGGGTGAAGAATGATACTTGGAATGAGAGTAGTATTAGCAATGGAACTATCACACTCCC
ATGCAGAATAAAACAAATTGTAAACATGTGGCAGGAAGTAGGAAGAGCAATGTATGCCCCTCCTATCAAA
GGACAAATTAATTGTACATCGAATATTACAGGGCTGCTACTAACAAGAGATGGTGGTCAGACTAATAGCA
CCAACAACGACACTGAGACCTTCAGACCTACAGGAGGAGATATAAGGGACAATTGGAGGAGTGAATTATA
TAAATATAAAGTAGTAAAAATTGAACCATTAGGAATAGCACCCACCAGGGCAAAAAGAAGAGTGGTGCAA
AGAGAAAAAAGAGCAGTGGGAACGATGGGAGCGTTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-234c10;PRT/1;HIV-1>
SAAEQLWVTVYYGVPVWKDATTTLFCASDAKAYDTEVHNVWATHACVPTDPNPQEVVMGNVTEYFNMWTN
NMVEQMHEDVISLWDQSLKPCVKLTPLCVTLNCTNLVNTTCNGTTNNNTTCTGTANNDTNTNSTRWVYQA
MAGEIKNCSFNITTNIRDKIKKEYALFNRLDIVPIDDENKNTGNTTSYRLISCNTSVITQACPKVTFEPI
PIHYCAPAGFAILKCNDKKFNGTGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEEETVIRSSNFSNNAKI
IIVQLNETVRINCTRPNNNTRRSIHIGPGRAFYATGDIIGDIRQAHCNISGEEWRRTLKRITIKLGEQFN
KTKISYNQSSGGDPEIVRHSFNCQGEFFYCDTSGLFNSTWVKNDTWNESSISNGTITLPCRLKQIVNMWQ
EVGRAMYAPPIKGQINCTSNITGLLLTRDGGQTNSTNNDTETFRPTGGDIRDNWRSELYKYKVVKIEPLG
IAPTRAKRRVVQREKR
<U-236c2;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAGGGGGATCATGAGGAATTACTTGTGGAAATGGGGCAT
CATGCTCCTTGGGATATTGATGATCTGTAGTGCTACAGACAAATTGTGGGTCACAGTCTATTATGGGGTG
CCTGTGTGGAAAGAAGCATCCACCACTCTATTTTGTGCATCAGATGCTAAAGCCTATGATACAGAGGTAC
ATAATGTTTGGGCCACACATGCCTGTGTACCCACAGATCCCAATCCACACGAATTAGAATTGGAAAATGT
GACAGAAGATTTTAACATGTGGAAAAATGACATGGTCGAACAGATGCATGAGGATATAATCAGTTTATGG
GATCAAAGCCTAAAACCATGTGTAAAATTAACCCCACTCTGTGTTACTTTAAATTGCAGTGATGCTTTAA
CTTGCAATAGGACATCAAATAGCAGTAGTACTTCAAATTGCAGTAACTGGGAACCGATAGAAGAAATAAA
AAATTGCTCTTTCAATATTACCACAAGCATAGAAAATAAGATGCAGAAAAAGTCTGCATTTTTTGATGCC
CTTGATGTAGTACAAATAGATGATACTAGTTATAGGTTGATAAATTGTAACACCTCAGTCATTACACAGG
CCTGTCCAAAGATATCCTTTGAGCCAATTCCCATACATTATTGTGCCCCGGCTGGTTTTGCGCTTCTAAA
GTGTAAGGATCCGAAATTCAATGGAACAGGGCCATGTAAATATGCTAGCTCAGTACAGTGTACACATGGA
ATTAGGCCGGTAGTATCAACTCAACTGCTGCTAAATGGCAGTCTAGCAGAAGAAGATATAGTAATTAGAT
CTGCCAATTTCTCGGACAACACCAAAGCCATAATAGTACAACTAAAAGAACCTGTAATAATTAATTGCAC
AAGACCCAACAACAATACAAGACAAAGTGTACATATAGGACCAGGGAGCGCACTTTATACAACAGATATA
ATAGGAGATATAAGAAAAGCACATTGTAACATTAGTAGAGCAGACTGGACTAAAGCTTTAAACCAGACAG
TCATAAAATTAAGAGAACAATTTAAGAATAAAACAATAGTCTTTAATCAATCCTCAGGAGGGGATCCAGA
AATTGTAATGCACACTTTTAATTGTGGAGGGGAATTTTTCTATTGTAATTCAACAAAACTGTTTAATAGT
ACTTGGAATGGGACTGAACCAGGAGAGTCAAATGACACTGTAATCATACTCCCATGCAGAATAAAACAAA
TTATAAATATGTGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATCAGAGGACAAATTAGATGTAC
ATCAAATATTACAGGGCTGCTACTAACAAGAGATGGGGGAAATGAGACCACTAAAAACGGGACTGAGACC
TTCAGACCTGGAGGAGGAAATATGAAGGACAATTGGAGAAGTGAATTATATAAATATAAAGTGGTAAAAA
TTGAACCATTAGGAGTAGCACCCACCAAGGCAAAAAGAAGAGTGGTGCAGAGAGAAAAAAGAGCAATAGG
GGCATTCGGAGCTATGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-236c2;PRT/1;HIV-1>
SATDKLWVTVYYGVPVWKEASTTLFCASDAKAYDTEVHNVWATHACVPTDPNPHELELENVTEDFNMWKN
DMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCSDALTCNRTSNSSSTSNCSNWEPIEEIKNCSFNITTS
IENKMQKKSAFFDALDVVQIDDTSYRLINCNTSVITQACPKISFEPIPIHYCAPAGFALLKCKDPKFNGT
GPCKYASSVQCTHGIRPVVSTQLLLNGSLAEEDIVIRSANFSDNTKAIIVQLKEPVIINCTRPNNNTRQS
VHIGPGSALYTTDIIGDIRKAHCNISRADWTKALNQTVIKLREQFKNKTIVFNQSSGGDPEIVMHTFNCG
GEFFYCNSTKLFNSTWNGTEPGESNDTVIILPCRIKQIINMWQEVGKAMYAPPIRGQIRCTSNITGLLLT
RDGGNETTKNGTETFRPGGGNMKDNWRSELYKYKVVKIEPLGVAPTKAKRRVVQREKR
<U-260c3;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAAAGTGAAGGGGATCAGGAAGAATTGTCAGCGCTTGTGGAGATG
GGGCACGATGCTCCTTGGGATGTTAATGATATGTAGTGCTGCAGAGCAATTGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGGAGAGAAGCAAACACCACTCTATTCTGTGCCTCAGATGCTAAAGCACAGGTTGCAG
AGGCACATAATGTATGGGCCACACATGCCTGTGTACCCACAGACCCTAGCCCACAAGAAGTAGTAATGGA
AAATGTGACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGATATAATCAGT
TTATGGGATCAAAGTCTAAAGCCATGTGTGAAATTAACCCCACTCTGCGTTACTTTAAATTGCACTAATG
TGGGTTGCACTGGTAATACTACTGGACCCAATTGTACTTCTTTGACTGATCATAATAGTAATCTTACTTG
GGGAATGGAGAAAGGAGAAATAAAAAATTGCTCTTTCAATGTCACCAGTATAACAAATAAGATGCAGAAA
GAATATGCACTTTTTTATAAACTTGATGTAATGCCAATGGATAGTACAGATAATACAACGTATACACTGA
TAAATTGTAACCCCTCAGTCATTACACAGGCCTGTCCAAAGGTATCTTTTGAACCCATTCCTATACATTA
TTGTACCCCGGCTGGTTTTGCGATTCTAAAGTGTAATGATAAGACATTCAATGGATCAGGACCATGTACA
AATGTCAGTACAGTACTATGTACACATGGAATTAGGCCAGTAGTGTCAACTCAACTACTGTTAAATGGCA
GTCTAGCAGAAGAGGAGGTAATAGTCAGGTCCGAGAATTTCTCGGACAATACTAAAATCATAATAGTACA
GCTGAATAAAACTGTAGAAATTAATTGTACAAGACCCAATAACAATACAAGAAAAAGTATACATATAGCA
CCAGGAAAAGCATTCTATGCAACAGGTGATATAATAGGAGATATAAGACAAGCACATTGTAACATCAGTG
AAACAAAATGGGTGAACACTTTAAAACAGGTAGTTACAAAATTAAGGGAACAATATGGGAATAAAACAAT
AGCCTTTAATCAATCCTCAGGAGGGGATCCAGAAATTGTAACGCATAGTTTTAATTGTGGAGGAGAATTT
TTCTACTGTAATACATCACGGCTGTTTAATAGTAATTGGACTGGGAATGGAACGACTGAGTCAGGAAATA
GCACAATCATACTTCCATGCAGAATAAAACAAATTATAAACAGATGGCAGGAAGTAGGAAAAGCAATGTA
TGCCAATCCCATTAGTGGACCAATCAACTGTTCATCAAACATTACAGGGCTGCTATTAACAAGAGATGGT
GGTAAAGTGACCAATGACACCACCGAGACCTTCAGACCTTGGGGTGGAGATATGAGGGACAATTGGAGAA
GTGAACTATATAAATATAAAGTAGTAAGAATTGAGCCATTAGGACTAGCACCCACCAGGGCAAAGAGAAG
AGTGGTGCAGAGAGAAAAGAGAGCAATAACATTAGGAGCTATGTTCCTTGGGTTCTTGGGAGCAGCAGGA
AGCACT
<U-260c3;PRT/1;HIV-1>
SAAEQLWVTVYYGVPVWREANTTLFCASDAKAQVAEAHNVWATHACVPTDPSPQEVVMENVTENFNMWKN
NMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCTNVGCTGNTTGPNCTSLTDHNSNLTWGMEKGEIKNCS
FNVTSITNKMQKEYALFYKLDVMPMDSTDNTTYTLINCNPSVITQACPKVSFEPIPIHYCTPAGFAILKC
NDKTFNGSGPCTNVSTVLCTHGIRPVVSTQLLLNGSLAEEEVIVRSENFSDNTKIIIVQLNKTVEINCTR
PNNNTRKSIHIAPGKAFYATGDIIGDIRQAHDNISETKWVNTLKQVVTKLREQYGNDTIAFNQSSGGDPE
IVTHSFNCGGEFFYCNTSRLFNSNWTGNGTTESGNSTIILPCRIKQIINRWQEVGKAMYANPISGPINCS
SNITGLLLTRDGGKVTNDTTETFRPWGGDMRDNWRSELYKYKVVRIEPLGLAPTRAKRRVVQREKR
<U-275c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGAGATCAGGAAGAATTGGCAGCGCTTGTGGAGATG
GGGCATGATGCTCCTTGGGATGTTGATGATCAGTAGTGCTGAAGAAGATTTGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGGAAAGAAGCAGAGACCACTTTATTTTGTGCATCAGATGCTAAAGCATATAACACAG
AGGCACATAATGTGTGGGCCACACATGCCTGTGTACCAACAGACCCTAGCCCACAAGAAGTATTATTGGT
AAATGTGACAGAAAATTATAACATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGATATAATTAGT
TTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCGCTTTGTGTTACTTTAAATTGCACTAATG
TGAATTGCACTCATGAGAATGGTACCACTACCGAGTGCGGTAATAATGGGATACAGATGGAGAAAGGAGA
AATGAAAAACTGCTCTTTCAATATTACCACAAGCATAAAAAATAAGATGCAGAAAGAATATGCACTTTTG
TATAAACTAGATTTAGCATCAATAGGTAATGATAATACAAGCTATACTTTGATAAGTTGTAACACCTCAG
TCATTACACAGGCCTGTCCAAAGATATCCTTTGAACCAATTCCAATACATTATTGTGCCCCGGCTGGTTT
TGCGATTCTAAAATGTAATGATAAGAACTTCAAGGGAACAGGATCATGTAAAAATGTCAGCACAGTACAA
TGTACACATGGAATTAAGCCAGTAGTGTCAACTCAATTGTTGTTAAATGGCACTTTAGCAGAAACAGAGG
TAGTAATTAGATCTGAAAATATCACAGACAATGCTAAAACCATAATAGTACAACTGAAGGACCCTGTAAA
AATTAATTGTACAAGACCTGGCAACAATACAGCAAGAAGCATACATATGGGACCGGGGAGAGCATTTTCT
GCAACAGGACAAATAATAGGAAATATAAGACAAGCACATTGTAACCTTAGTAGAACAGAATGGGATGACA
CTTTAAAAAAGATAGCTAAGAAATTAGGAGAACAATTTAGGAATAAAAGTATAGCCTTTAATCAATCCTC
AGGAGGGGACCCAGAAATTGTAATGCACAGTTTTAATTGTGGAGGGGAATTTTTTTACTGTAATACATCA
CAGCTGTTTAATAGTACTTGGTGGAACAATGGTACTAGGAATGATGCTGCAAGGTCAAATAGCACTGAAC
CTATCACACTCCGGTGCAGTATAAAGCAAATTATAAACAGATGGCAGGAAGTAGGAAAAGCAATGTATGC
CCCTCCATCAGGGGAAACGTTACATGTAACTCAAGTATTACAGGGCTACTCTTAATAAGAGATGGGTGGG
AACAGTAATGAGTCTACTGAGACCTTCAGACCTCAGGGAGGAAATATGAAGGACAATTGGAGAAGTGAAT
TATACAAATATAAAGTAGTAAAAATTGAGCCATTAGGAGTAGCACCCACCAAGGCAAAGAGAAGAGTGGT
GCAGAGAGAAAAAAGAGCAGTGGGACTAGGAGCTGTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-275c1;PRT/1;HIV-1>
SAEEDLWVTVYYGVPVWKEAETTLFCASDAAKAYNTEAHNVWATHACVPTDPSPQEVLLVVTENYNMWKN
NMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCTNVNCTHENGTTTECGNNGIQMEKGKMKNCSFNITTS
IKNKMQKEYALLYKLDLASIGNDNTSYTLISCNTSVITQACPKISFEPIPIHYCAPAGFAILKCNDKNFK
GTGSCKNVSTVQCTHGIKPVVSTQLLLNGTLAETEVVIRSENITDNAKTIIVQLKDPVKINCTRPGNNTA
RSIHMGPGRAFSATGQIIGNIRQAHCNLSRTEWDDTLKKIAKKLGEQFRNKSIAFNQSSGGDPEIVMHSF
NCGGEFFYCNTSQLFNSTWWNNGTRNDAARSNSTEPITLRCSIKQIINRWQEVGKAMYAPPIRGNVTCNS
SITGLLLIRDGGNSNESTETFRPQGGNMKDNWRSELYKYKVVKIEPLGVAPTKAKRRVVQREKR
<U-279c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGATGGGGATAAAGAAGAATTACTGGTGGAGATGGGGCCC
GATGCTCCTTGGGATATTGATGACCTATAGTGCAGCAGAATTTTGGGTCACAGTCTACTATGGAGTGCCA
GTGTGGAAAGAAACAACCACCACTCTATTTTGTGCATCAGATGCCAAAGCATATGATACAGAGGCACATA
ATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTAGTATTGGAAAAGGTGAC
AGAAGAGTTTAACATGTGGAAAAATAGCATGGTAGAACAGATGCATGAGGATATAATCAGTTTATGGGAT
CAAAGTCTAAAGCCATGTGTAAAACTAACCCCACTCTGTGTTACTTTAAGTTGCACTGATTGTAATGGTA
CTAGCCCTGAGTGTGCGAAGAATGCTAGTACTACTACCACTAGTAGTAAGGGATTGATAGATAAAGGGGA
AATAAAAAACTGCTCTTTCAATGCCACCACACACATAATGGATAAGGTGCAGAAAGAATATGCATTATTT
TATAACACTGATTTAGTACAAATAGAGGGTGAGAAATCTGATAATAATACTAGATATAGGTTAATAAGTT
GTAACACCTCAGTCATTAAACAGGCCTGTCCAAAGGTATCTTTTGAGCCAATTCCCATACATTATTGTGC
CCCGGCTGGTTTTGCGATTCTAAAGTGTAAAGATAAGAATTTCAATGGAACAGGAAAATGTTACAATGTC
AGCACAGTACAATGTACACATGGAATTAGGCCAGTAATGTCAACTCAACTGCTGTTAAATGGCAGCCTAG
CAGAAGAAGAAATAGTAATTAGATGTGCCAATTTCTCGAACAATGCTAAAACCATAATAGTACATCTGAA
TGAATCTGTAGAAATTAACTGCACAAGACCCAACAACGATACAAGGAAAAGTATAAATATAGGACCAGGG
AGAGCATGGTATGCAGCAGGAGAAATAATAGGAAATATAAGAAAAGCATATTGTAACATTAGCAGAGCAA
AATGGAACAACACTTTAAAACATGTAGTTGAAAAAACTAAGAAAACAATTTGGAAATAAACAATAAACTT
TACACAACACGCAGGAGGGGACCTAGAAATTGTGACGCATAGTTTTAATTGTGGAGGGGAATTCTTCTAC
TGCAACACAACACAGCTGTTTAATAGTACTTGGCCTAAGAATGGTACTTGGAATGGTACTGGTAGTGACA
TTATCACACTCCCATGCAAAATAAAACAGATTATAAACATGTGGCAGGAGGTAGGAAAAGCAATGTATGC
CCCTCCCATCAGCGGACTAATTAGATGTTCATCAAATATTACAGGGCTGCTATTAACAAGAGATGGTGGT
AAGGGTAATGGCACAAATGATACAGAGATCTTCAGACCAGGAGGAGGAGATATGAGGGACAATTGGAGAA
GTGAATTATATAAATATAAAGTAGTAGAAATTGAGCCAATAGGACTAGCACCCACCAAGGCAAAGAGAAG
AGTGGTGCAGAGAGAAAAAAGAGCAGTGGGAACGCTGGGAGCTATGTTCCTTGGGTTCTTGGGAGCAGCA
GGAAGCACT
<U-279c1;PRT/1;HIV-1>
SAAEFWVTVYYGVPVWKETTTTLFCASDAKAYDTEAHNVWATHACVPTDPNPQEVVLEKVTEEFNMWKNS
MVEQMHEDIISLWDQSLKPCVLTPLCVTLSCTDCNGTSPECAAKNASTTTTSSKGLIDKGEIKNCSFNAT
THINDKVQKEYALFYNTDLVQIEGEKSDNNTRYRLISCNTSVIKQACPKVSFEPIPIHYCAPAGFAILKC
KDKNFNGTGKCYNVSTVQCTHGIRPVMSTQLLLNGSLAEEEIVIRSANFSNNAKTIIVHLNESVEINCTR
PNNDTRKSINIGPGRAWYAAGEIIGNIRKAYCNISRAKWNNTLKHVVELRKQFGNKTINFTAQHAGGDLE
IVTHSFNCGGEFFYCNTTQLFNSTWPKNGTWNGTGSDIITLPCKIKQIINMWQEVGKAMYAPPISGLIRC
SSNITGLLLTRDGGKGNGTNDTEIFRPGGGDMRDNWRSELYKYKVVEIEPIGLAPTKAKRRVVQREKR
<U-284c3;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGCGAAGGGGATCAGGAAGAGTTGTCAACACTTATGGAGATG
GGGCACCATGCTCCTTGGGATGTTGATGATTTGTAGTGCTGCAGAAAACTTGTGGGTCACAGTCTACTAT
GGGGTACCTGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATCGAATGCTAAAGCATATGAGACAG
AGGTGCATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTAGTATTGGG
AAATGTGACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGATGTAATTAGT
TTGTGGGACCAAAGCTTAAAGCCATGTGTAAAATTGACCCCACTCTGTGTTACTTTACATTGCACTGATT
GTGAGAATACTATTACTGGGGGGAATAATACTAATAGTAAATGCAATGAGGATAAGGGGAATACTACTGC
CACTATATTGATAGAGAAAGGAGAGATGAAAAACTGCTCTTTTAATGTCACCACAGACCTAAGAGATAAG
ATGCAGAAAGAATATGCACTTGATGTAGTACCATTAGACAGTACTAATACCAGCTATAAGTTAGTAAGTT
GTAACACCTCAGTCATTACACAGGCCTGTCCAAAGGTATCTTTTGAGCCAATTCCAATACATTTCTGTGC
CCCAGCTGGTTTTGCGATTCTAAAGTGTAACAATAAAACGTTTGATGGAAAAGGACCATGTACAAATGTC
AGTACAGTGCGATGTACACATGGAATTAAACCAGTAGTGTCAACTCAACTGCTGTTAAATGGCAGTCTAG
CAGAAGAAGAGATAGTGATTAGATCTGAAAATTTCTCGAACAATGCTAAAACCATAATAGTACGGCTAAA
TAAAACTGTAGAAATTAATTGTACAAGACCCAACAACAACACAAGCAAAGGTATACATATGGGACCAGGG
AGGGCATTTTATGCAACAGGAAGAATAGTAGGAGATATAAGACAAGCACATTGTAACATTAGTAACGCAG
ATTGGACAAATACTTTAAAACAGGTAGCTAGGAAATTAAGGGAACAATATGTGAATAAAACAATAGCCTT
TAAGCCACCCTCAGGAGGGGACCCAGAAGTTGTACTGCACACTTTTAATTGTAGAGGGGAATTTTTCTAC
TGTAATTTATCAAGAATGTTTAATAGTAGTTTTAATTCAACACAACTGTCTAATTATTCAGAAGATACTG
GGACCATCACAGTCCCATGCAGAATAAAACAATTTATAAACATGTGGCAGGAAGTAGGAAAAGCAATGTA
TGCCCCTCCCATCAGAGGAGAAATTAATTGTTCATCAAAGATTACAGGATTGTTATTAACAAGAGACGGT
GGCAATAGCAATGGGACTGAGATTTTCAGACCTGGAGGAGGAGATATGAGGGACAATTGGAGAAGTGAAT
TATACAAATATAAAGTAGTAAGAATTGAACCATTAGGATTAGCACCCACCAAGGCAAAGAGAAGAGTGGT
GCAGAGAGAAAAAAGAGCAGCAGTGACAATGGGAGCAATGTTCCCTGGGTTCTTGGGAGCAGCAGGAAGC
ACT
<U-284c3;PRT/1;HIV-1>
SAAENLWVTVYYGVPVWKEATTTLFCASNAKAYETEVHNVWATHACVPTDPNPQEVVLGNVTENFNMWKN
NMVEQMHEDVISLWDQSLKPCVKLTPLCVTLHCTDCENTITGGNNTNSKCNEDKGNTTATILIEKGEMKN
CSFNVTTDLRDKMQKEYALDVVPLDSTNTSYKLVSCNTSVITQACPKVSFEPIPIHFCAPAGFAILKCNN
KTFDGKGPCTNVSTVRCTHGIKPVVSTQLLLNGSLAEEEIVIRSENFSNNAKTIIVQLNKTVEINCTRPN
NNTSKGIHMGPGRAFYATGRIVGDIRQAHCNISNADWTNTLKQVARKLREQYVNKTIAFKPPSGGDPEVV
LHTFNCRGEFFYCNLSRMFNSSFNSTQLSNYSEDTGTITVPCRIKQFINMWQEVGKAMYAPPIRGEINCS
SKITGLLLTRDGGNSNGTEIFRPGGGDMRDNWRSELYKYKVVRIEPLGLAPTKAKRRVVQREKR
<U-306c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAGAGTGAAGGGGATCAGGAAGAATTATCAGCACTTATGGAGATG
GGGCACCGTGCTCCTTGGGATGTTGATGATCTGTAGTGCTGTAGAACAATTGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGGAAAGAAGCAACCACCACTTTATTTTGTGCATCAGATGCTAAAGCATATGACACAG
AGGCACATAATGTCTGGGCCACACATGCCTGTGTACCTACAGACCCTAACCCACAAGAAGTAGTATTGGA
AAATGTGACAGAAGATTCTAACATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGATATAATCAGT
TTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCACTCTGTGTTACTCTAAATTGCACTGATT
TCAATTGTACTAGTTCCAGCAATACTACTAATAGCACTTGCATTGGTACCCATCGGACTACTAATACCGA
TGGTAGGGAGAAATTGGAAATGGAGGTAGGAGAAATAAAAAACTGCTCTTTCAATGTCACCACAAGCATA
AGGAATAAGGTACAGAAAGAATATGCACTTTTTTATAAACTTGATGTAATGCCAATAGATAGTACGAGCT
ATACATTGATACATTGCAACACTTCAACCATTACACAGGCCTGTCCAAAGGTATCCTTTGAACCAATTCC
TATACATTATTGTGCCCCGGCTGGTTTTGCGATTCTAAAGTGTAACAATAAGACGTTCAGTGGAAAAGGA
CCATGTAAAAATGTCAGCACAGTTCAATGTACACATGGAATTAGGCCAGTAGTGTCAACTCAACTGCTGT
TAAATGGTAGTCTAGCAGAAGAAGAGATAGTAATTAGGTCTGACAATTTCTCGGACAATGCTAAAATCAT
AATAGTACACCTAAATAAATCTATAGAAATTAATTGTACAAGACCCAACAATAATACAAGAAAAAGAATA
TCGATGGGGCCGGGAAGAGTATATTATACAACAGGACAAATAATAGGAGATATAAGAAAAGCACATTGTA
ATATTAGTGGAGAAGAATGGAATAGAACGTTAAAAGGGATAGTTATAAAATTAAGAGAACAATTTGGGAA
GAATAAAACAATCATCTTTGATAGATCCTCAGGAGGGGACCTAGAAATTGAAATGCATAGTTTTAATTGT
GGAGGAGAGTTCTTCTACTGTAATACAACAAAACTATTTAATAGTGCTTGGAATGAGTCAGGTTACAATG
GGACAAATTCTAATGGAACTATTACACTCCCATGCAGAATAAGACAAATTGTAAACAGGTGGCAGGAAGT
AGGAAAAGCAATGTATGCCCCTCCCATCACAGGACAAATTAGGTGTTCATCAAATATTACAGGACTAATA
TTAACAAGAGATGGTGGTAACAGTAGCAATAGTAGTAATGTGAATGAGACCTTCAGACCTACAGGAGGAG
ATATGAGGGACAATTGGAGAAGTGAATTATATAAATATAAAGTAATACGAATTGAGCCAATAGGAGTAGC
ACCCACCAAGGCAAAGAGAAGAGTGGTGCAGAGAGAGAAAAGAGCAGTGGGAACGCTAGGAGCTATGTTC
CTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-306c1;PRT/1;HIV-1>
SAVEQLWVTVYYGVPVWKEATTTLFCASDAKAYDTEAHNVWATHACVPTDPNPQEVVLENVTEDSNMWKN
NMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCTDFNCTSSSNTTNSTCIGTHRTTNTDGREKLEMEVGE
IKNCSFNVTTSIRNKVQKEYALFYKLKVMPIDSTSYTLIHCNTSTITQACPKVSFEPIPIHYCAPAGFAI
LKCNNKTFSGKGPCKNVSTVQCTHGIRPVVSTQLLLNGSLAEEEIVIRSDNFSDNAKIIIVHLNKSIEIN
CTRPNNNTRKRISMGPGRVYYTTGQIIGDIRKAHCNISIEEWNRTLKGIVIKLREQFGKNKTIIFDRSSG
GDLEIEMHSFNCGGEFFYCNTTKLFNSAWNESGYNGTNSNGTITLPCRIRQIVNRWQEVGKAMYAPPITG
QIRCSSNITGLILTRDGGNSSNSSNVNETFRPTGGDMRDNWRSELYKYKVIRIEPIGVAPTKAKRRVVQR
EKR
<U-332c14;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAAAGCGAAGGAGATGAAGAAGCATTGGCAGCACTTGTGGAAAGG
GGGCATCATGCTCCTTGGGATGTTAATGATCTGTAGTGCTGCACCAAACTTGTGGGTCACAGTCTATTAT
GGGGTACCTGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATCAGATGCTAAAGCATACAAAACAG
AGGCTCATAATGTCTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTAGTATTGGA
AAATGTGACAGAAAATTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGATATAATTAGT
CTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCACTCTGTGTTACTTTAAATTGCACTAAGT
TAAATAATTGCACTGAGTTGCAGAATGATACTACGAATAGTACTACGTTGGAGAATGGTACTTATTGCAT
TAAGGTGGAGAATAAAACTAATATAAGGGAAGAAATGACAAATTGCTCTTTCAATATTACCACAAGTGTA
AGAGATAAGGTGCATAAACAATATGCTCTCTTCTATAGATTTGATTTAGTACCAATAGAGAGTGAAAATA
AGAATACTAGCTCTAATAATAGCTTTAGATTGATAAATTGTAATACCTCAATCATTACACAGTCCTGTCC
AAAGGTAACCTTTGAGCCAATTCCCATACATTATTGTACCCCAGCTGGTTTTGCGATTCTAAAGTGTAAT
GATAAGAAGTTCAATGGAAAAGGGCCATGTACAAATGTCAGCACAGTACAATGTACACATGGAATTAAAC
CAGTAGTGTCAACTCAACTGCTGTTAAATGGCAGTCTAGCAGAAGAAGAGGTAGTAATTAGATCTGAAAA
CTTCACAAACAATGCTAAAACCATAATAGTACAGCTGAACGAGACTGTAGAAATTAATTGTACAAGACCT
AGCAACAATACAAGAAAAAGTATAACTATAGGACCAGGGAGAGCATTTTTTACAACAGGGGATGTAATAG
GAAATATAAGGCAAGCATATTGTAACGTTAGTAGGGCAAAATGGAATAACACTTTAAGACAGATAGTTAC
AAAACTAAGAGAACAATTTGAGAATAAAACAATAATTTTTAAGTCATCCTGGGGAGGGGACCCAGAAATT
GTAACTCACACTTTTAATTGTGGAGGAGAATTTTTCTACTGTAATACAACACCACTGTTTAATAGTACCT
GGGATAATAGTACCTGGGATTGGAATAATACTGAAGAGTCAAACAGCACTCCCATTGTACTCACATGCAG
AATAAAACAAATTGTAAATATGTGGCAGGAGGTAGGAAAAGCAATGTATGCCCCTCCCATCAGAGGACAA
ATTTGGTGTTCATCAAATATTACAGGACTGCTATTAACAAGAGATGGTGGAATAAATAATACGGGAAATG
AGACCTTCAGACCTGCAGGAGGAGATATGAGGGACAATTGGAGAAGTGAATCATATAAATATAAAGTAGT
AAGAATTGAACCATTAGGAGTGGCACCCACCAAGGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCA
GTGGGAACAATAGGAGCTATGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-332c14;PRT/1;HIV-1>
SAAPNLWVTVYYGVPVWKEATTTLFCASDAKAYKTEAHNVWATHACVPTDPNPQEVVLENVTENFNMWKN
NWVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCTKLNNCTELQNDTTNSTTLENGTYCIKVENKTNIREE
MTNCSFNITTSVRDKVHKQYALFYRFDLVPIEDENKNTSSNNSFRLINCNTSIITQSCPKVTFEPIPIHY
CTPAGFAILKCNDKKFNGKGPCTNVSTVQCTHGIKPVVSTQLLLNGSLAEEEVVIRSENFTNNAKTIIVQ
LNETVEINCTRPSNNTRKSITIGPGRAFFTTGDVIGNIRQAYCNVSRAKWNNTLRQIVTKLREQFENKTI
IFKSSSGGDPEIVTHTFNCGGEFFYCNTTPLFNSTWDNSTWDWNNTEESNSTPIVLTCRIKQIVNMWQEV
GKAMYAPPIRGQIVCSSNITGLLLTRDGGINNTGNETFRPAGGDMRDNWRSESYKYKVVRIEPLGVAPTK
AKRRVVQREKR
<U-356c1;DNA;HIV-1>
AGAAAGAGCAGAAGACAGTGGCAATGAAAGCGAAGGAGACCAGGAAGAACTATCAGCGCTTGTGGAGATG
GGGCACGATGCTCCTTGGGATGTTGATGATCTGTAGTGCTACAGAAAAATTGTGGGTCACAGTCTACTAT
GGGGTACCTGTGTGGAAAGAAGCAACTACCACTCTATTTTGTGCATCAGATGCTAAAGCATATGATACGG
AGGTACATAATGTTTGGGCCACACATGCCTGTGTACCCACAGACCCCAACCCACAAGAAGTAGTATTGGT
AAATGTAACAGAAAAGTTTAACATGTGGAAAAATAACATGGTAGAACAAATGCATGAGGACATAATCAAT
CTATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACCCCGCTCTGTATTACTTTAAATTGCTCTGATG
TTAGAAATTGCACTGAGCAGGGGAATGATACTGCCGCTAGTACTTGTATTGATTGGAAGACTAATGGTAG
TGAGAAAGTGATGGAGAAAGGAGAAATAAAAAACTGCTCTTTCAATATTACAACAAACATAAGGGACAAG
GTGAAGGAAGAGTATGCACTTTTTTATAAAATTGATATAGCACCAATAGATAATGATACTACTAGCTATA
GGTTGATAAATTGTAACACCTCAGTCATTACACAGGCCTGTCCAAAGGTATCCTTTGAGCCAATTCCCAT
ACATTATTGTGCCCCGGCTGGTTTTGCGATTCTAAAATGTGGAGATAAGAAGTTCAATGGAACAGGACTA
TGTAAAAATGTCAGCACAGTACAATGTACACATGGAATTAGGCCAGTAGTGTCAACTCAACTGCTGTTAA
ACGGCAGTCTAGCAGAAGAAGATGTAATAATTAGATCTGCCAATTTCACAGACAATGCTAAAAACATAAT
AGTACAGCTGAAGGAATCTGTAGAAATTACTTGTATAAGACCCAACAATACAAGAAAAAGTATTCATATA
GGACCAGGGAAAACATTTTTTACAACAGAAATAATAGGAAATATAAGACAAGCATATTGTACCCTTGATG
GAACAAAATGGAATAACACTTTAGCACAGATAGTTGAACAATTAAGGGGACAATTTGGAAATAAAACAAT
AGACTTTAAGCAACCCTCAGGAGGGGACCCAGAAGTTATAATGCACAAGTTTAATTGTGGAGGGGAATTT
TTCTACTGTAATTCAACACAACTGTTTAATAGTACTTGGCCACTAAATGGTACTAGATCAGGTGGCACTG
AAGGAAGCACTGAAGGAAATATCACACTCCCATGTAAAATAAAACAAATTATAAACAGGTGGCAGGAAGT
AGGAAAAGCAATGTATGCCCCTCCCATCAAAGGAATAATTAGATGTTCATCGAATATTACAGGGCTGATA
TTAACAAGAGATGGTGGGGAGGGCAAGAACGATACCAACAGTACCGAGATCTTCAGACCTGGAGGAGGAG
ATATGAGGGACAATTGGAGAAGTGAATTATATAAATATAAAGTAGTACGAATTGAACCATTAGGAGTAGC
ACCCACCAAGGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCAGTGGGGATGCTAGGAGCTATGTTC
CTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-356c1;RT/1;HIV-1>
SATEKLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHACVPTDPNPQEVVLVNVTEKFNMWKN
NMVEQMHEDIINLWDQSLKPCVKLTPLCITLNCSDVRNCTEQGNDTAASTCIDWKTNGSEKVMEKGEIKN
CSFNITTNIRDKVKEEYALFYKIDIAPIDNDTTSYRLINCNTSVITQACPKVSFEPIPIHYCAPAGFAIL
KCGDKKFNGTGLCKNVSTVQCTHGIRPVVSTQLLLNGSLAEEDVIIRSANFTDNAKNIIVQLKESVEITC
IRPNNTRKSIHIGPGKTFFTTEIIGNIRQAYCTLDGTKWNNTLAQIVEQLRGQFGNKTIDFKQPSGGDPE
VIMHKFNCGGEFFYCNSTQLFNSTWPLNGTRSGGTEGSTEGNITLPCKIKQIINRWQEVGKAMYAPPIKG
IIRCSSNITGLILTRDGGEGKNDTNSTEIFRPGGGDMRDNWRSELYKYKVVRIEPLGVAPTKAKRRVVQR
EKR
<U-374c1;DNA;HIV-1>
AGAAGAGCAGAAGACAGTGGCAATGAAAGTGAAGGAGACCAGGAAGAATTATCAGAACTTATGGAGATGG
GGCATCTTGCTCCTTGGGATATTAATGATCTGTAGTGCTGCAGAAAAATTGTGGGTAACAGTCTATTATG
GGGTACCTGTGTGGAGAGAAGCAAACACCACTTTATTTTGTGCATCAGATGCTAAAGCATATGATACAGA
AGTACATAATGTCTGGGCCACACATGCCTGTGTGCCCACAGACCCCAACCCACAAGAAGTAGTATTGGGA
AATGTGACAGAATATTTTAATATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGATATAATCAGTT
TATGGGATCAAAGCCTAAAGCCATGTGTAAAATTAACTCCACTCTGTGTTACTTTAAATTGCACTGATGC
AGTCTGTACTTCAAATTGCACTAATTCCACTGGTACGTCCACTCCTATTCCCACCACTGTTAGCAGTGAG
GACAAAGGAGAAATAAAAAACTGCTCTTTCAATGTCACCACAAGCATAAAAGATAGGATACAGAGAGAAT
ATGCAACTTTTTATAAGCTTGATGTAGTACCAATAGATGATGATGATAATACTAGAGATGATAATAATAC
TAGTAATAATAATACTAGTAACCCTAGTAAGACTCTCTATAGGTTGATAAATTGTAACACCTCAGCCCTT
ACACAGGCCTGTCCAAAGGTATCCTTTGAACCAATTCCCATACATTATTGTGCCCCAGCTGGTTTTGCGA
TTCTAAAGTGTAACAATAAGACATTCGATGGATCGGGACCATGTACAAATGTCAGCACAGTACAATGTAC
ACATGGAATTAGGCCAGTAGTGTCAACTCAATTGCTGTTAAATGGCAGTCTAGCAGAAGGAGATATAGTA
ATCAGATCTGAAAATTTCTCGAACAATGCTAAAACCATAATAGTACAGCTGAAGGAATCTATAAGCATTA
ATTGTACAAGACCCAACAACAATACAAGAAAAAGTATACATATAGGACAAGGAAGGGCATTTTATACAAC
AGGAGATATAATAGGAGATATAAGAAAAGCACATTGTAACGTTAGTAGAGAAGGTTGGAATAACGCTGTA
AACCGACTAGTTGAAAAATTAAAAGAACAATTTGGAAAAAGAAAAACAATAAAATTTAAGCCATCCTCAG
GAGGGGACCCAGAGATTGTAATGCACATGTTTAATTGTGGAGGGGAGTTTTTCTACTGTAATACATCAAA
ACTGTTTAATGTTGTTAATGATACTTGGATGGGATCAAATGACACTGGAGAAATCGAGCTCCCATGTAGA
ATAAAACAAATCGTAAGCATGTGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATCAGAGGACAAA
TTAGATGTTCATCAGATATCACAGGGCTGCTATTAACAAGAGATGGTGGTAAGGATGACAACAACACAAT
TGGAAATGAAACCTTCAGACCTGGAGGAGGAGATATGAGGGACAATTGGAGAAGTGAATTATATAAATAT
AAAGTAGTAAAAATTCAACCACTAGGAATAGCACCCACCAAGGCAAAGAGAAGAGTGGTGCAGAGAGAAA
AAAGAGCAGTGGGAGCACTAGGAGCTATGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACT
<U-374c1;PRT/1;HIV-1>
SAAEKLWVTVYYGVPVWREANTTLFCASDAKAYDTEVHNVWATHACVPTDPNPQEVVLGNVTEYFNMWKN
NMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCTDAVCTSNCTNSTGTSTPIPTTVSSEDKGEIKNCSFN
VTTSIKDRIQREYATFYKLDVVPIDDDDNTTDDNNTSNNNTSNPSKTLYRLINCNTSALTQACPKVSFEP
IPIHYCAPAGFAILKCNNKTFDGSGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEGDIVIRSENFSNNAK
TIIVQLKESISINCTRPNNNTRKSIHIGQGRAFYTTGDIIGDIRKAHCNVSREGWNNAVNRLVEKLKEQF
GKRKTIKFKPSSGGDPEIVMHMFNCGGEFFYCNTSKLFNVVNDTWMGSNDTGEIELPCRIKQIVSMWQEV
GKAMYAPPIRGQIRCSSDITGLLLTRDGGKDDNNTIGNETFRPGGGDMRDNWRSELYKYKVVKIQPLGIA
PTKAKRRVVQREKR
<HXB2;DNA;HIV-1>
ATGAGAGTGAAGGAGAAATATCAGCACTTGTGGAGATGGGGGTGGAGATGGGGCACCATGCTCCTTGGGA
TTGATGATCTGTAGTGCTACAGAAAAATTGTGGGTCACAGTCTATTATGGGGTACCTGTGTGGAAGGAAG
ACCACCACTCTATTTTGTGCATCAGATGCTAAAGCATATGATACAGAGGTACATAATGTTTGGGCCACAC
GCCTGTGTACCCACAGACCCCAACCCACAAGAAGTAGTATTGGTAAATGTGACAGAAAATTTTAACATGT
AAAAATGACATGGTAGAACAGATGCATGAGGATATAATCAGTTTATGGGATCAAAGCCTAAAGCCATGTG
AAATTAACCCCACTCTGTGTTAGTTTAAAGTGCACTGATTTGAAGAATGATACTAATACCAATAGTAGTA
GGGAGAATGATAATGGAGAAAGGAGAGATAAAAAACTGCTCTTTCAATATCAGCACAAGCATAAGAGGTA
GTGCAGAAAGAATATGCATTTTTTTATAAACTTGATATAATACCAATAGATAATGATACTACCAGCTATA
TTGACAAGTTGTAACACCTCAGTCATTACACAGGCCTGTCCAAAGGTATCCTTTGAGCCAATTCCCATAC
TATTGTGCCCCGGCTGGTTTTGCGATTCTAAAATGTAATAATAAGACGTTCAATGGAACAGGACCATGTA
AATGTCAGCACAGTACAATGTACACATGGAATTAGGCCAGTAGTATCAACTCAACTGCTGTTAAATGGCA
CTAGCAGAAGAAGAGGTAGTAATTAGATCTGTCAATTTCACGGACAATGCTAAAACCATAATAGTACAGC
AACACATCTGTAGAAATTAATTGTACAAGACCCAACAACAATACAAGAAAAAGAATCCGTATCCAGAGAG
CCAGGGAGAGCATTTGTTACAATAGGAAAAATAGGAAATATGAGACAAGCACATTGTAACATTAGTAGAG
TTTAAGCAATCCTCAGGAGGGGACCCAGAAATTGTAACGCACAGTTTTAATTGTGGAGGGGAATTTTTCT
TGTAATTCAACACACAACTTTAATAGTACTTGGTTTAATAGTACTTGGAGTACTGAAGGGTCAAATAACA
GAAGGAACTGACACAATCACCCTCCCATGCAGAATAAAACAAATTATAAACATGTGGCAGAAAGTAGGAA
GCAATGTATGCCCCTCCCATCAGTGGACAAATTAGATGTTCATCAAATATTACAGGGCTGCTATTAACAA
GATGGTGGTAATAGCAACAATGAGTCCGAGATCTTCAGACCTGGAGGAGGAGATATGAGGGACAATTGGA
AGTGAATTATATAAATATAAAGTAGTAAAAATTGAACCATTAGGAGTAGCACCCACCAAGGCAAAGAGAA
GTGGTGCAGAGAGAAAAAAGA
<HXB2;PRT/1;HIV-1>
MRVKEKYQHLWRWGWRWGTMLLGMLMICSATEKLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWA
HACVPTDPNPQEVVLVNVTENFNMWKNDMVEQMHEDIISLWDQSLKPCVKLTPLCVSLKCTDLKNDTNTN
SSGRMIMEKGEIKNCSFNISTSIRGKVQKEYAFFYKLDIIPIDNDTTSYKLTSCNTSVITQACPKVSFEP
PIHYCAPAGFAILKCNNKTFNGTGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSVNFTDNAKT
IVQLNTSVEINCTRPNNNTRKRIRIQRGPGRAFVTIGKIGNMRQAHCNISRAKWNNTLKQIASKLREQFG
NKTIIFKQSSGGDPEIVTHSFNCGGERFYCNSTQLFNSTWFNSTWSTEGSNNTEGSDTITLPCRIKQIIN
WQXVGKAMYAPPISGQIRCSSNITGLLLTRDGGNSNNESEIFRPGGGDMRDNWRSELYKYKVVKIEPLGV
PTKAKRRVVQREKR
Claims (63)
1.一种免疫原性组合物,其包括:
(a)分离多肽包括,或分离多聚核苷酸编码,一个第一gp120氨基酸序列,其中,第一gp120序列包括至少gp120的V2、V3和C4结构域和:
(i)第一gp120序列在一个或多个以下位点缺少一个或多个半胱氨酸残基:54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418和445;和/或
(ii)第一gp120序列在除下述位点以外的位点含有一个或多个额外的半胱氨酸残基:24,29,34,54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418,445,493,495,499-501,503-508和510;
计数从HIV gp120的HXB-2株的gp120的N端甲硫氨酸开始;
其中,第一gp120序列不是在V1结构域具有一个或多个附加的半胱氨酸的gp120序列的G亚型或在V4结构域具有一个或多个附加的半胱氨酸的gp120序列的E亚型;和一个药学上可接受的载体。
2.如权利要求1的免疫原性组合物,其中所述的第一gp120序列额外地含有V1结构域。
3.如权利要求1的免疫原性组合物,其中所述的免疫原性组合物额外地含有佐剂。
4.如权利要求1的免疫原性组合物,其中所述的第一gp120序列包括一个天然发生的gp120序列。
5.如权利要求4的免疫原性组合物,其中所述的第一gp120序列包括从初始HIV分离物来源的gp120序列。
6.如权利要求1的免疫原性组合物,其包括含有第一gp120序列的多肽。
7.如权利要求1的免疫原性组合物,其包括编码第一gp120序列的多聚合苷酸。
8.如权利要求1的免疫原性组合物,其中所述的第一gp120序列在一个或多个以下位点缺少一个或多个半胱氨酸残基:54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418和445。
9.如权利要求8的免疫原性组合物,其中所述的第一gp120序列在一个或多个以下位点缺少一个或多个半胱氨酸残基:54,74,119,126,157,205,218,228,239,247,331,378或385。
10.如权利要求1的免疫原性组合物,其中所述的第一gp120序列在除下述位点以外的位点含有一个或多个额外的半胱氨酸残基:24,29,34,54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418,445,493,495,499-501,503-508和510。
11.如权利要求10的免疫原性组合物,如果一个或多个额外的半胱氨酸残基不存在于gp120的V1区,其中所述的第一gp120序列则在除下述为点以外的位点含有一个或多个额外的半胱氨酸残基:54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418或445。
12.如权利要求1的免疫原性组合物,其中所述的第一gp120序列包括奇数个半胱氨酸。
13.如权利要求12的免疫原性组合物,其中所述的组合物包括含有第一gp120序列的多肽,且第一gp120序列中的一个半胱氨酸与其他多肽共价键连接。
14.如权利要求13的免疫原性组合物,其中所述的共价键包括二硫键。
15.如权利要求13的免疫原性组合物,其中所述的其他多肽包括第二gp120序列。
16.如权利要求15的免疫原性组合物,其中所述的第二gp120序列与第一gp120序列相同,所述的gp120序列形成一个同源二聚体。
17.如权利要求15的免疫原性组合物,其中所述的第二gp120序列与第一gp120序列不相同,所述的gp120序列形成一个异源二聚体。
18.如权利要求13的免疫原性组合物,其中所述的其他多肽包括gp41氨基酸序列。
19.如权利要求12的免疫原性组合物,其中所述的组合物包括含有第一gp120序列的多肽,在该gp120序列中的一个半胱氨酸共价键地结合到一个选自细胞特异性结合半族、药物、免疫刺激性寡核苷酸或免疫原性载体蛋白的试剂。
20.如权利要求1的免疫原性组合物,其中所述的多肽包括,或多聚核苷酸编码含有第一gp120序列的融合蛋白。
21.如权利要求1的免疫原性组合物,其中所述的第一gp120序列与选白下列序列的gp120的每一个V1,V2,V3和C4结构域具有至少约99%的同一性:SEQ ID NO:2,4,6,8,10,12,14,16,18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48,50,52,54,56,58,60,62,64,66,68,70,72,74,76,78,80,82,84,86,88,90,92,94,96,98,100,102,104,106,108,110,112,114,116,118,120,122,124,126,128,130,132,134和136。
22.如权利要求21的免疫原性组合物,其中所述的第一gp120序列含有至少选自下列序列的gp120的V1,V2,V3和C4区:SEQ ID NO:2,4,6,8,10,12,14,16,18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48,50,52,54,56,58,60,62,64,66,68,70,72,74,76,78,80,82,84,86,88,90,92,94,96,98,100,102,104,106,108,110,112,114,116,118,120,122,124,126,128,130,132,134和136。
23.含有第一gp120氨基酸序列的分离多肽,其中所述的第一gp120序列包括至少gp120的V2,V3和C4结构域,和:
(a)第一gp120序列在一个或多个以下位点缺少一个或多个半胱氨酸残基:54,74,119,126,157,205,218,228,239,247,331,378或385;和/或
(b)如果一个或多个额外的半胱氨酸残基不存在于gp120的V1结构域,则第一gp120序列在除下述位点以外的位点含有一个或多个额外的半胱氨酸残基:54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418或445。
计数从HIV gp120的HXB-2株的gp120的N端甲硫氨酸开始;
其中,第一gp120序列不是在V4结构域具有一个或多个附加的半胱氨酸的gp120序列的E亚型。
24.如权利要求23的多肽,其中所述的第一gp120序列额外地包括V1结构域。
25.如权利要求23的多肽,其中所述的第一gp120序列在一个或多个以下位点缺少一个或多个半胱氨酸残基:54,74,119,126,157,205,218,228,239,247,331,378或385。
26.如权利要求23的多肽,其中如果一个或多个额外的半胱氨酸残基不存在于gp120的V1结构域,则所述的第一gp120序列在除下述位点以外的位点含有一个或多个额外的半胱氨酸残基:54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418或445。
27.如权利要求23的多肽,其中所述的第一gp120序列包括奇数个半胱氨酸。
28.如权利要求27的多肽,其中所述的gp120序列中的半胱氨酸与其他多肽共价键地结合。
29.如权利要求28的多肽,其中所述的共价键是二硫键。
30.如权利要求28的多肽,其中所述的其他多肽包括一个第二gp120序列。
31.如权利要求30的多肽,其中所述的第二gp120序列与第一gp120序列相同,所述的gp120序列形成一个同源二聚体。
32.如权利要求30的多肽,其中所述的第二gp120序列与第一gp120序列不相同,所述的gp120序列形成一个异源二聚体。
33.如权利要求28的多肽,其中所述的其他多肽包括一个gp41氨基酸序列。
34.如权利要求27的多肽,其中所述的gp120序列中的一个半胱氨酸共价键地结合到一个选自细胞特异性结合半族、药物、免疫刺激性寡核苷酸或免疫原性载体蛋白的试剂。
35.如权利要求23的多肽,其中所述的多肽包括含有第一gp120序列的融合多肽。
36.如权利要求35的多肽,其中所述的融合多肽含有异源信号序列。
37.如权利要求36的多肽,其中所述的异源信号序列选自单纯疱疹病毒糖蛋白D(gD-1)信号序列和人组织血浆酶原激活因子信号序列。
38.如权利要求35或36的多肽,其中所述的多肽含有附加表位。
39.一个含有第一gp120氨基酸序列的分离多肽,其中第一gp120序列与选自下列序列的gp120的每一个V1,V2,V3和C4结构域至少具有大约99%的同一性:SEQ ID N0:2,4,6,8,10,12,14,16,18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48,50,52,54,56,58,60,62,64,66,68,70,72,74,76,78,80,82,84,86,88,90,92,94,96,98,100,102,104,106,108,110,112,114,116,118,120,122,124,126,128,130,132,134和136。
40.如权利要求39的多肽,其中所述的第一gp120序列具有至少选自下列序列的gp120的V1,V2,V3和C4结构域:SEQ ID NO:2,4,6,8,10,12,14,16,18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48,50,52,54,56,58,60,62,64,66,68,70,72,74,76,78,80,82,84,86,88,90,92,94,96,98,100,102,104,106,108,110,112,114,116,118,120,122,124,126,128,130,132,134和136。
41.一种编码权利要求23-27或35-40的任何一项的多肽的分离多聚核苷酸。
42.如权利要求41的多聚核苷酸,其中所述的多聚核苷酸是为在特定种的宿主细胞表达的优化的密码子。
43.如权利要求41的多聚核苷酸,其中所述的多聚核苷酸编码与选自下列序列的gp120的每一个V1,V2,V3和C4结构域至少具有大约99%的同一性的gp120序列:SEQ ID N0:2,4,6,8,10,12,14,16,18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48,50,52,54,56,58,60,62,64,66,68,70,72,74,76,78,80,82,84,86,88,90,92,94,96,98,100,102,104,106,108,110,112,114,116,118,120,122,124,126,128,130,132,134和136。
44.如权利要求43的多聚核苷酸,其中所述的多聚核苷酸包括选自下列序列的gp120核酸序列:SEQ ID NO:1,3,5,7,9,11,13,15,17,19,21,23,25,27,29,31,33,35,37,39,41,43,45,47,49,51,53,55,57,59,61,63,65,67,69,71,73,75,77,79,81,83,85,87,89,91,93,95,97,99,101,103,105,107,109,111,113,115,117,119,121,123,125,127,129,131,133,135或其亚序列,其中亚序列编码至少gp120的V1,V2,V3和C4结构域。
45.一种含有权利要求41的多聚核苷酸的载体。
46.如权利要求45的载体,其中所述的载体包括一个表达载体。
47.如权利要求45的载体,其中所述的载体包括一个病毒载体。
48.一个含有权利要求45的载体的宿主细胞。
49.如权利要求48的宿主细胞,其中所述的宿主细胞选自哺乳动物细胞或细菌细胞。
50.一种制备含有第一gp120氨基酸序列的多肽的方法,所述方法包括:
(a)将权利要求45的载体导入细胞;
(b)表达多肽。
51.如权利要求50的方法,其中所述的细胞是在体内的。
52.如权利要求50的方法,其中所述的细胞是培养的。
53.如权利要求52的方法,另外包括从培养基中回收多肽。
54.一种制备含有第一gp120氨基酸序列的多肽的方法,所述方法包括:
(a)培养权利要求48的宿主细胞,其中所述的宿主细胞包括表达载体,宿主细胞在适于表达多肽的条件下被培养;
(b)从培养基中回收多肽。
55.一种用含有第一gp120序列的多肽免疫动物的方法,该方法包括向动物投药权利要求1的免疫原性组合物。
56.一种诊断方法,其包括:
(a)使来源于被治疗者的生物样品与含有gp120氨基酸序列的分离多肽接触,其中gp120序列包括至少gp120的V2,V3和C4结构域和;
(i)gp120序列在一个或多个以下位点缺少一个或多个半胱氨酸残基:54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418和445;和/或
(ii)gp120序列在除下述位点以外的位点含有一个或多个额外的半胱氨酸残基:24,29,34,54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418,445,493,495,499-501,503-508和510;
计数从HIV gp120的HXB-2株的gp120的N端甲硫氨酸开始;
其中,第一gp120序列不是在V1结构域具有一个或多个附加的半胱氨酸的gp120序列的G亚型或在V4结构域具有一个或多个附加的半胱氨酸的gp120序列的E亚型;和
(b)确定该生物样品是否具有可特异性结合到分离多肽的抗体。
57.如权利要求56的诊断方法,其中所述的gp120序列额外的包括V1结构域。
58.一种诊断方法,其包括分析从被治疗者来源的生物样品,以鉴定该样品是否含有多肽包括,或多聚核苷酸编码gp120氨基酸序列,该gp120序列:
(a)在一个或多个以下位点缺少一个或多个半胱氨酸残基:54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418和445;和/或
(b)在除下述位点以外的位点含有一个或多个额外的半胱氨酸残基:24,29,34,54,74,119,126,131,157,196,205,218,228,239,247,296,331,378,385,418,445,493,495,499-501,503-508和510;
计数从HIV gp120的HXB-2株的gp120的N端甲硫氨酸开始。
59.如权利要求58的诊断方法,其中所述的gp120序列不是在V1结构域具有一个或多个附加的半胱氨酸的gp120序列的G亚型或在V4结构域具有一个或多个附加的半胱氨酸的gp120序列的E亚型。
60.如权利要求58的诊断方法,其中所述的分析包括使样品在适于结合的条件下与特异性结合gp120序列的抗体结合。
61.如权利要求58的诊断方法,其中所述的分析包括使样品多聚核苷酸在适于杂交的条件下与特异性和编码gp120序列的核苷酸序列杂交的核酸分子结合。
62.如权利要求61的诊断方法,其中所述的核酸分子是一对扩增引物中的一个,所述分析包括使样品多聚核苷酸在适于扩增的条件下与两个扩增引物接触,所述检测包括检测扩增产物是否产生。
63.如权利要求61的诊断方法,其中所述的核酸分子是固定到固定相的核酸探针。
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EP1940867A2 (en) * | 2005-09-06 | 2008-07-09 | The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services | Hiv gp120 crystal structure and its use to identify immunogens |
WO2010042760A2 (en) * | 2008-10-08 | 2010-04-15 | The Administrators Of The Tulane Educational Fund | Compositions, methods, and kits for enhancing the immunogenicity of pathogenic antigens |
WO2012139099A2 (en) * | 2011-04-08 | 2012-10-11 | Duke University | Herpes simplex virus vaccine |
EP2739300B1 (en) | 2011-07-05 | 2019-06-19 | Duke University | N-terminal deleted gp120 immunogens |
EP2763699A4 (en) | 2011-10-03 | 2015-05-20 | Univ Duke | VACCINE |
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US4376110A (en) * | 1980-08-04 | 1983-03-08 | Hybritech, Incorporated | Immunometric assays using monoclonal antibodies |
US4366241A (en) * | 1980-08-07 | 1982-12-28 | Syva Company | Concentrating zone method in heterogeneous immunoassays |
US4517288A (en) * | 1981-01-23 | 1985-05-14 | American Hospital Supply Corp. | Solid phase system for ligand assay |
CA1291031C (en) * | 1985-12-23 | 1991-10-22 | Nikolaas C.J. De Jaeger | Method for the detection of specific binding agents and their correspondingbindable substances |
DE69130741T2 (de) * | 1990-05-16 | 1999-07-29 | Dana Farber Cancer Inst Inc | Immunogene peptide, antikörper sowie deren verwendungen im zusammenhang mit der cd4-rezeptorbindung |
ZA975889B (en) * | 1996-07-08 | 1998-02-23 | Genentech Inc | HIV envelope polypeptides and vaccine. |
US6716429B1 (en) * | 1997-10-01 | 2004-04-06 | Dana-Farber Cancer Institute, Inc. | Stabilization of envelope glycoprotein trimers by disulfide bonds introduced into a gp 41 glycoprotein ectodomain |
EP1198468A4 (en) * | 1999-06-25 | 2003-07-30 | Progenics Pharm Inc | STABILIZED VIRAL ENVELOPE PROTEINS AND USES |
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- 2004-06-10 US US10/866,527 patent/US20050025779A1/en not_active Abandoned
- 2004-06-10 AU AU2004247146A patent/AU2004247146A1/en not_active Abandoned
- 2004-06-10 KR KR1020057023830A patent/KR20060041179A/ko not_active Application Discontinuation
- 2004-06-10 MX MXPA05013334A patent/MXPA05013334A/es not_active Application Discontinuation
- 2004-06-10 EP EP04755049A patent/EP1633308A4/en not_active Withdrawn
- 2004-06-10 CN CNA2004800163060A patent/CN1809381A/zh active Pending
- 2004-06-10 WO PCT/US2004/018672 patent/WO2004110384A2/en active Application Filing
- 2004-06-10 CA CA002528005A patent/CA2528005A1/en not_active Abandoned
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108640977A (zh) * | 2018-06-18 | 2018-10-12 | 上海大学 | 特异性结合HIV上包膜糖蛋白gp120的多肽及其应用 |
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US20050025779A1 (en) | 2005-02-03 |
EP1633308A2 (en) | 2006-03-15 |
MXPA05013334A (es) | 2006-05-19 |
WO2004110384A3 (en) | 2005-06-02 |
KR20060041179A (ko) | 2006-05-11 |
CA2528005A1 (en) | 2004-12-23 |
AU2004247146A1 (en) | 2004-12-23 |
EP1633308A4 (en) | 2008-06-25 |
WO2004110384A2 (en) | 2004-12-23 |
IL172273A0 (en) | 2006-04-10 |
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