Molecular Archeology of HIV

描述（由申请人提供）：由于逆转录病毒（如HIV-1）进化如此迅速，从几十年前检索到的病毒基因序列实际上是分子“化石”。这些化石序列可以用来提供一种特定微生物在早期时间点存在的无可争议的证据，以验证否则无法测试的历史推断，并提供对艾滋病流行病当前演变和动态的洞察。它们照亮了原本会丢失的远古部分，并可以提供测试有关医学重要病毒的起源，发病机制，适应，传播，持久性和传播动力学的重要假设的手段。控制艾滋病毒的斗争需要尽可能地了解其目前的遗传多样性，而这种了解可以通过在历史遗传变异的背景下观察当代基因序列来实现。除了少数例外，“分子考古学”的观点迄今为止还没有被用于HIV-1 M组，这是本提案的重点。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。为了实现这一目标，我们将目标1。使用20世纪70年代的档案标本来揭示HIV-1在北美的起源和出现的历史; 2.从1960年甚至更早的石蜡包埋组织样本中恢复和分析近全长包膜基因，如果可能的话，还包括基因组HIV-1序列; 3.研究非洲中部HIV-1 M组的早期遗传多样性，以及它如何通过筛选大量的HIV-1档案样本并对所得数据集进行序列和系统发育分析来了解这一重要地区目前的遗传多样性。至关重要的是，我们已经收集了大量的档案标本，其中许多来源尚未在艾滋病毒研究领域得到广泛考虑，我们将通过这些标本来阐明艾滋病毒进化的早期阶段（从发现艾滋病的时候开始，追溯到20世纪60年代甚至更早）直到今天。我们的专业知识和跟踪记录使我们处于独特的位置来进行这项重要的研究。 公共卫生相关性：这项工作与公共卫生有关，因为它涉及艾滋病毒/艾滋病的自然历史：艾滋病流行病如何起源，传播和演变到今天。它将提供对HIV-1 M组过去和现在的遗传多样性和动态的了解，因此可能有助于控制目前的流行病和防止艾滋病病毒未来向人类传播。

DESCRIPTION (provided by applicant): 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, to validate historical inferences that could otherwise not be tested, and to provide insight into the current evolution and dynamics of the AIDS pandemic. They light up portions of the deep past that would otherwise be lost, and can provide the means to test important hypotheses about the origins, pathogenesis, adaptation, spread, persistence, and transmission dynamics of medically important viruses. The battle to control HIV requires the best possible understanding of its current genetic diversity, and such understanding can best be achieved by viewing contemporary gene sequences in the context of historical genetic variation. With just a handful of 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 accomplish this we will aim 1. to use archival specimens from the 1970s to uncover the history of the origin and emergence of HIV-1 in North America; 2. to recover and analyze near- full-length envelope gene and, if possible, genomic HIV-1 sequence from multiple paraffin- embedded tissue samples from the 1960 and perhaps earlier; 3. to investigate the early genetic diversity of HIV-1 group M in central Africa and how it informs understanding of the current genetic diversity in this important region by screening large numbers of archival samples for HIV-1 and conducting sequence and phylogenetic analyses on the resulting data set. Crucially, we have assembled a massive collection of archival specimens, 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 1960s and perhaps even earlier) right up to the present day. Our expertise and track record make us uniquely positioned to conduct this important research. PUBLIC HEALTH RELEVANCE: This work is relevant to public health since it is concerned with the natural history of HIV/AIDS: how the AIDS pandemic originated, spread, and evolved up to and including the present day. It will provide understanding of the past and present genetic diversity and dynamics of HIV-1 group M and may thus be of use in controlling the current pandemic and preventing future jumps of AIDS viruses into humans.