THE EMERGENCE OF HIV GENETIC DIVERSITY IN CAMEROON

喀麦隆艾滋病毒基因多样性的出现

• 批准号: 6663063
• 负责人: NATHAN D WOLFE
• 金额: $ 7.56万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6663063
• 关键词: HIV infections; clinical research; communicable disease diagnosis; diagnosis design /evaluation; enzyme linked immunosorbent assay; epidemiology; gel mobility shift assay; gene frequency; genetic recombination; human immunodeficiency virus 1; human subject; nucleic acid sequence; polymerase chain reaction; virus genetics; western blottings

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.

人体免疫机能丧失病毒（艾滋病毒）目前在全球造成的死亡率超过任何其他单一传染病，是非洲的主要死因。 诊断检测和疫苗是解决这一问题的核心工具。 然而，这些工具的有效性可能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并不完全清楚。 这项拟议中的研究调查了将新型HIV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整个猴免疫缺陷病毒（SIV）基因组的跨物种传播出现，而且通过非人慢病毒和完全适应人类的病毒HIV-1之间的重组事件中出现的单个基因或基因组片段出现。虽然人类对非人类灵长类动物的狩猎是这一界面的前沿，但据我们所知，他们从未被系统地研究过。 这项建议包括四个相互关联的目标。 首先，我们将使用全病毒ELISA和Western Blot评估喀麦隆猎人中HIV和HIV相关慢病毒的流行情况。 其次，我们将通过聚合酶链反应（PCR）和异源双链迁移率测定（HMA）在三个独立的基因组区域，这将揭示广泛的系统发育关系的HIV基因组的这三个区域的阳性分离株。 第三，我们将研究所选分离株的详细遗传镶嵌结构，以评估重组的基因组位点，使用全长基因组测序和系统发育分析。 第四，在完成目标一至三的过程中，我们将从喀麦隆的艾滋病毒分离物中研制试剂，并调整和实地测试适合于在喀麦隆继续监测艾滋病毒的HMA。 拟议的研究将通过在艾滋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指导，为主要研究人员提供重要的职业发展。