The Emergence of HIV: A Molecular Archeology Approach

因为像HIV-1这样的逆转录病毒进化得如此之快，从几十年前检索到的病毒基因序列实际上是分子“化石”。这种化石序列可以用来提供一种给定微生物在早期存在的无可争议的证据，并验证历史推断，否则无法进行测试。它们照亮了原本会丢失的远古部分，并为我们提供了测试关于医学上重要病毒的起源和进化轨迹的至关重要的假设的手段。尽管控制艾滋病毒的斗争始终需要对其目前的遗传多样性有最好的了解，但只有在历史遗传变异的背景下观察当代基因序列才能实现这种了解。只有少数著名的 例外的是，“分子考古学”的观点迄今为止还没有被用于HIV-1 M组，这是该建议的焦点。该项目的总体目标是通过恢复并分析从其过去收集的信息，做出全面和综合的努力来了解HIV-1 M组的未来。要做到这一点，我们将1。使用档案标本来揭示艾滋病毒在北美出现的历史，以确定海地是否是艾滋病毒-1 M组亚型B在发达国家传播之前的“垫脚石”; 2.通过优化DMA提取方案，确定高灵敏度PCR筛选引物， 探索汇集样本的方法，并筛选我们存档的非洲组织标本的一小部分。至关重要的是，我们已经收集了大量的档案材料，其中许多来源尚未在艾滋病毒研究领域得到广泛考虑，我们将利用这些材料来阐明艾滋病毒进化的早期阶段（从发现艾滋病的时间开始，追溯到1955年甚至更早）。

Because retroviruses like HIV-1 evolve so rapidly, viral genetic sequences retrieved from just a few decades before present are effectively molecular 'fossils'. Such fossil sequences can be used to provide indisputable evidence of the existence of a given microbe at an early time point, and to validate historical inferences that could otherwise not be tested. They light up portions of the deep past that would otherwise be lost, and give us the means to test critically important hypotheses about the origins and evolutionary trajectories of medically important viruses. Although the battle to control HIV will always require the best possible understanding of its current genetic diversity, such understanding can only be achieved by viewing contemporary gene sequences in the context of historical genetic variation. With just a handful of notable exceptions the 'molecular archeology' perspective has to date not been exploited with respect to HIV-1 group M, the focus of this proposal. The overarching aim of this project is to make a comprehensive and integrated effort to understand the future of HIV-1 group M by recovering then analyzing information gleaned from its past. To do this we will 1. use archival specimens to uncover the history of the emergence of HIV in North America to determine whether Haiti was the "stepping stone" of HIV-1 group M subtype B before it spread around the developed world; and 2. investigate the evolution of HIV-1 in central Africa at an unprecedented early time point by optimizing DMA extraction protocols, identifying high-sensitivity PCR screening primers, exploring methods for pooling samples, and screening a small subset of our archived African tissue specimens. Crucially, we have assembled a massive collection of archival materials, many from sources that have not yet been widely considered in the field of HIV research, with which we will illuminate the remarkably unstudied early phase of HIV evolution (from around the time of the discovery of AIDS, back to 1955 and perhaps even earlier).