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.
This work is directly relevant to public health since it is concerned with understanding how HIV/AIDS originated and spread worldwide and HIV-1 evolves over the long term. This knowledge has implications both for the control of this pandemic and potentially for reducing the likelihood of future viral outbreaks.
