The Emergence of HIV: A Molecular Archeology Approach

HIV 的出现：分子考古学方法

• 批准号: 7140582
• 负责人: MICHAEL WOROBEY
• 金额: $ 18.43万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140582
• 关键词: AIDS; biochemical evolution; clinical research; emerging infectious disease; epidemiology; history of life science; human immunodeficiency virus 1; human tissue; tissue resource /registry

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).

因为像HIV-1这样的逆转录病毒进化得如此之快，从几十年前提取的病毒基因序列实际上是分子“化石”。这样的化石序列可以用来提供无可争辩的证据，证明某一特定微生物在早期时间点的存在，并验证否则无法验证的历史推论。它们照亮了原本会被遗忘的那部分深刻的过去，并为我们提供了检验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总是需要对其当前的遗传多样性有最好的了解，但这种了解只能通过在历史遗传变异的背景下观察当代基因序列来实现。只有少数几个值得注意的

项目成果

A challenge to the ancient origin of SIVagm based on African green monkey mitochondrial genomes.

基于非洲绿色猴子线粒体基因组的Sivagm古代起源的挑战。

• DOI: 10.1371/journal.ppat.0030095
• 发表时间: 2007-07
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Wertheim JO;Worobey M
• 通讯作者: Worobey M

Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960.

• DOI: 10.1038/nature07390
• 发表时间: 2008-10-02
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Worobey, Michael;Gemmel, Marlea;Teuwen, Dirk E.;Haselkorn, Tamara;Kunstman, Kevin;Bunce, Michael;Muyembe, Jean-Jacques;Kabongo, Jean-Marie M.;Kalengayi, Raphael M.;Van Marck, Eric;Gilbert, M. Thomas P.;Wolinsky, Steven M.
• 通讯作者: Wolinsky, Steven M.

The isolation of nucleic acids from fixed, paraffin-embedded tissues-which methods are useful when?

• DOI: 10.1371/journal.pone.0000537
• 发表时间: 2007-06-20
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Gilbert MT;Haselkorn T;Bunce M;Sanchez JJ;Lucas SB;Jewell LD;Van Marck E;Worobey M
• 通讯作者: Worobey M