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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 确定细胞免疫反应是否影响异性恋赞比亚夫妇之间的HIV传播，并控制早期感染，以及TRIM5A多态性是否会影响暴露的个体的感染。在350个长期感染的赞比亚个体中已经鉴定出了类似于HLA的插科打，NEF和策略多态性。这些已用于研究144名受试者的逃生，恢复和补偿性突变，在感染后两年内纵向纵向跟踪。两次卢旺达传输对的接近长度进化枝A艾滋病毒序列和随访1年的艾滋病毒序列也揭示了有关免疫驱动进化的新信息。 Microsoft研究合作者正在研究与I类和II类HLA等位基因和等位基因相关的多态性，用于杀伤细胞免疫蛋白样受体（KIR）。 Kir2ds4*001等位基因与慢性感染伴侣和加速病毒传播的病毒载量较高有关（1）。 不利的HLA等位基因A*3601和DRB*0102与563个血清降低的病毒载荷相关，但在221名Seroconverter受试者中不相关，而有利的A*74，B*13，B*13，B*13，B*57或CW*18，以及A*30+CW*03+CW*03+CW*03等位基因均与重新负载相关，但仅在2个均与2）相关。与牛津的Goulder Lab的合作研究表明，Gag Capsid的显着差异主要是由于保护等位基因HLA -B*57，-5801和-8101和-8101以及与HLA独立的多态性相互依赖的多态性在与这些逃生中发生的，可能代表补偿性更改（3）。与UAB的Goepfert实验室的合作表明，神秘的表位会诱导免疫原性反应（4）。这些结果可能有助于设计更有效的疫苗。