THE EMERGENCE OF HIV GENETIC DIVERSITY IN CAMEROON

人类免疫缺陷病毒(艾滋病毒)现在造成的全球死亡人数比任何其他单一感染源都多，是非洲人死亡的主要原因。诊断化验和疫苗是解决这一问题的中心工具。然而，这些工具的有效性可能会受到艾滋病毒遗传多样性的限制。产生和维持这种多样性的力量还没有完全被理解。这项拟议的研究调查了将新的艾滋病毒遗传多样性引入人类群体的潜在关键自然机制。我们假设HIV的遗传多样性不仅通过猴免疫缺陷病毒(SIV)基因组的跨物种传播而出现，而且通过在非人类慢病毒和完全人类适应的HIV-1病毒之间的重组事件中单个基因或基因组片段的出现而出现。虽然非人类灵长类动物的人类猎人处于这一界面的第一线，但据我们所知，他们从未被系统地检查过。这项提议包括四个相互关联的目标。首先，我们将使用完整的病毒ELISA和Western Blot来评估艾滋病毒和艾滋病毒相关慢病毒在喀麦隆猎人中的流行情况。其次，我们将通过聚合酶链式反应(PCR)和异源双链迁移率分析(HMA)在三个独立的基因组区域对阳性分离株进行鉴定，这将揭示HIV基因组这三个区域之间广泛的系统发育关系。第三，我们将使用全长基因组测序和系统发育分析，检查选定菌株的详细遗传马赛克结构，以评估重组的基因组位置。第四，在完成目标一至目标三的过程中，我们将开发喀麦隆艾滋病毒分离株的试剂，并调整和现场测试适合在喀麦隆继续监测艾滋病毒的HMA。拟议的研究将通过指导艾滋病病毒和相关病毒的流行病学、生态学和分子进化方面的指导，为主要研究人员提供重要的职业发展。

Human immunodeficiency virus (HIV) now causes more global mortality than any other single infectious agent and is the primary cause of death in Africa. Diagnostic assays and vaccines are central tools for addressing this problem. The effectiveness of these tools, however, may be limited by the genetic diversity of HIV. The forces that generate and maintain this diversity are incompletely understood. The proposed research investigates a potentially crucial natural mechanism for the introduction of novel HIV genetic diversity into the human population. We hypothesize that HIV genetic diversity emerges not only through the cross-species transmission of entire simian immunodeficiency virus (SIV) genomes, but also through the emergence of individual genes or genomic segments during recombination events between nonhuman lentiviruses and the fully human-adapted virus, HIV-1. While human hunters of nonhuman primates are at the front line of this interface, they have never, to our knowledge been systematically examined. This proposal includes four interrelated aims. First, we will assess the prevalence of HIV and HIV-related lentiviruses among hunters in Cameroon, using whole viral ELISAs and the Western Blot. Second, we will characterize positive isolates through the polymerase chain reaction (PCR) and heteroduplex mobility assay (HMA) at three independent genomic regions, which will reveal the broad phylogenetic relationships of these three regions of the HIV genome. Third, we will examine the detailed genetic mosaic structure of selected isolates in order to assess the genomic sites of recombination, using full-length genomic sequencing and phylogenetic analysis. Fourth, in the process of completing aims one through three, we will develop reagents from Cameroonian HIV isolates and adapt and field test an HMA appropriate for continued HIV surveillance in Cameroon. The proposed research will provide significant career development of the primary investigator through directed mentorship in the epidemiology, ecology, and molecular evolution of HIV and related viruses.