CTL AND HIV POLYMORPHISMS IN HETEROSEXUAL TRANSMISSION

异性传播中的 CTL 和 HIV 多态性

• 批准号: 8357448
• 负责人: Eric Hunter
• 金额: $ 7.43万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357448
• 关键词: Alleles; Capsid; Collaborations; Couples; Epitopes; Evolution; Funding; Gagging; Genetic Polymorphism; Grant; HIV; HLA-B Antigens; Heterosexuals; Immune; Immune response; Individual; Infection; Killer Cells; Length; Mutation; National Center for Research Resources; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Rwanda; Source; United States National Institutes of Health; Vaccines; Variant; Viral; Viral Load result; cost; design; follow-up; immunogenic; receptor; response; transmission process

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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子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恋夫妇之间的艾滋病毒传播，并控制早期感染，以及TRIM 5a多态性是否影响暴露个体的感染。在350名赞比亚慢性感染者中发现了HLA-like Gag、nef和pol多态性。这些已被用于研究逃逸，逆转，和补偿突变的144例急性感染的受试者，感染后纵向跟踪两年。两对卢旺达传播对的近全长进化枝A艾滋病毒序列（随访1年）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。KIR 2DS 4 *001等位基因与慢性感染伴侣的较高病毒载量和加速病毒传播相关（1）。 不利的HLA等位基因A*3601和DR B *0102与563例血清阳性受试者的较高病毒载量相关，但与221例血清转换受试者无关，而有利的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，但仅在血清转换组中（2）。与牛津大学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性等位基因HLA-B*57、-5801和-8101产生的逃逸突变以及与这些逃逸相关的共变HLA非依赖性多态性，这可能代表代偿性变化（3）。与UAB Goepfert实验室的合作表明，隐蔽表位可诱导免疫原性应答（4）。这些结果可能有助于设计更有效的疫苗。