Molecular Archeology of HIV

因为像HIV-1这样的逆转录病毒进化得如此之快， 在几十年前的今天是有效的分子化石。这样的化石序列可以 用于在早期时间点提供给定微生物存在的无可争议的证据， 并验证历史推断，否则无法测试。它们照亮了 否则就会丢失的深刻的过去，并提供测试至关重要的手段 关于医学上重要病毒的起源和进化轨迹的假设。 尽管控制艾滋病毒的斗争总是需要尽可能了解其 目前的遗传多样性，这种理解只能通过观察当代 基因序列在历史遗传变异的背景下。除了少数例外， 迄今为止，“分子考古学”的观点尚未在HIV-1方面得到利用 M组是本次提案的重点。这个项目的首要目标是使一个 全面和综合的努力，了解艾滋病毒-1 M组的未来， 然后分析从它过去收集的信息。 为了实现这一目标，我们将目标1。利用20世纪70年代的档案标本来揭示 HIV-1在北美出现的历史; 2.恢复接近全长的信封 1960年石蜡包埋的组织样本中的HIV-1基因和后来的基因组序列， 并利用其研究HIV-1的早期进化和预测表型; 3.到 通过筛选大样本，调查中非HIV-1 M组的早期遗传多样性 HIV-1的存档样本数量，并进行序列、系统发育和病毒 对产生的数据集进行紧急分析。最重要的是，我们已经组装了一个巨大的 档案标本的收集，许多来源尚未被广泛考虑 在艾滋病毒研究领域，我们将阐明显着未研究的早期阶段， 艾滋病毒的进化（从发现艾滋病的时候，回到20世纪60年代，也许 更早）。 我们的专业知识和业绩记录使我们处于独特的地位， 重要的研究。

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 provide 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 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 emergence of HIV-1 in North America; 2. to recover near-full-length envelope gene and, later, genomic HIV-1 sequence from a paraffin-embedded tissue sample from 1960, and use it to investigate the early evolution and predicted phenotype of HIV-1, and ; 3. to investigate the early genetic diversity of HIV-1 group M in central Africa by screening large numbers of archival samples for HIV-1 and conducting sequence, phylogenetic, and viral emergence 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). Our expertise and track record make us uniquely positioned to conduct this important research.