CTL AND HIV POLYMORPHISMS IN HETEROSEXUAL TRANSMISSION

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 确定细胞免疫反应是否影响赞比亚异性夫妇之间的艾滋病毒传播，并控制早期感染，以及TRIM5a基因多态是否影响暴露个人的感染。已在350名赞比亚慢性感染者中发现了类似于人类白细胞抗原的Gag、nef和pol基因的多态。这些研究已经被用来研究144名急性感染的受试者在感染后纵向追踪两年的逃逸、逆转和代偿性突变。两个卢旺达传播对的近全长分支A艾滋病毒序列，经过1年的跟踪，也揭示了免疫驱动进化的新信息。微软研究院的合作者正在研究与I类和II类HLA等位基因以及杀伤细胞免疫球蛋白样受体(KIR)等位基因相关的多态性。KIR2DS4*001等位基因与慢性感染伴侣中较高的病毒载量和加速病毒传播有关(1)。在563例血清转换患者中，不利的等位基因A*3601和DRB*0102与较高的病毒载量相关，但在221例血清转换患者中不相关；有利的A*74、B*13、B*57或Cw*18和A*30 Cw*03等位基因与病毒载量降低相关，但仅在血清转换组(2)。与牛津Goulder实验室的合作研究表明，Gag衣壳的显著变化主要是由于保护等位基因HLA-B*57、-5801和-8101产生的逃逸突变，以及与这些逃逸相关的协变性，这些逃逸可能代表代偿变化(3)。与UAB的Goepfert实验室的合作表明，隐蔽的表位诱导免疫原性反应(4)。这些结果可能有助于设计更有效的疫苗。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Determine whether cellular immune responses influence HIV transmission among heterosexual Zambian couples, and control early infection, and whether TRIM5a polymorphisms influence infection in exposed individuals. HLA-liked Gag, nef, and pol polymorphisms have been identified in 350 chronically infected Zambian individuals. These have been used to study escape, reversion, and compensatory mutations in 144 acutely infected subjects followed longitudinally for two years after infection. Near-full-length clade A HIV sequences for two Rwanda transmission pairs with 1 year of follow-up have also revealed new information on immune-driven evolution. Microsoft Research collaborators are examining polymorphisms related to class I and class II HLA alleles and alleles for killer cell immunoglobin-like receptors (KIR). The KIR2DS4*001 allele was associated with higher viral loads in chronically infected partners and accelerated viral transmission (1). Unfavorable HLA alleles A*3601 and DRB*0102 were associated with higher viral loads in 563 seroprevalent but not in 221 seroconverter subjects, whereas favorable A*74, B*13, B*57 or Cw*18, and A*30+Cw*03 alleles were associated with reduced viral loads, but only in the seroconverter group (2). Collaborative studies with the Goulder lab in Oxford showed that significant variation in the gag capsid is primarily due to escape mutations produced by protective alleles HLA-B*57, -5801, and -8101 and covarying HLA-independent polymorphisms arising in conjunction with these escapes which may represent compensatory changes (3). Collaborations with the Goepfert Lab at UAB has shown cryptic epitopes induce immunogenic responses (4). These results may help in designing more effective vaccines.