Molecular Archeology of HIV

由于像HIV-1这样的逆转录病毒进化如此之快，仅从一个 在此之前的几十年里都是有效的分子化石。这样的化石序列可以是 用来提供在早期某一特定微生物存在的无可争辩的证据， 并验证原本无法测试的历史推论。它们点亮了一部分 深厚的过去，否则就会丢失，并提供了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说。 尽管控制艾滋病毒的战斗总是需要对其最好的理解 目前的遗传多样性，这样的理解只能通过观察当代 历史遗传变异背景下的基因序列。除了少数几个例外， 分子考古学的观点到目前为止还没有被用来研究HIV-1 M组，这一提案的重点。这个项目的总体目标是使一个 通过康复全面和综合努力了解艾滋病毒-1 M组的未来 然后分析从它的过去收集的信息。 为了实现这一点，我们的目标是：1.使用20世纪70年代的档案标本来揭示 HIV-1病毒在北美出现的历史；2.恢复接近全长的信封 基因，后来又从20世纪60年代的石蜡包埋组织样本中提取了HIV-1基因组序列， 并用它来研究HIV-1的早期进化和预测的表型；3. 通过筛查大鼠研究中非HIV-1 M组早期遗传多样性 HIV-1的档案样本数量和正在进行的序列、系统发育和病毒 对生成的数据集进行涌现分析。至关重要的是，我们已经组建了一支庞大的 收集档案标本，其中许多来自尚未被广泛考虑的来源 在艾滋病毒研究领域，我们将用它来说明显著未被研究的早期阶段 艾滋病毒的进化(大约从发现艾滋病的时候，追溯到20世纪60年代，也许 甚至更早)。我们的专业知识和过往记录使我们处于独特的地位，可以进行这项工作 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.