genetic drift of hiv populations in culture遗传漂变的艾滋病人口文化.pdfVIP

Genetic Drift of HIV Populations in Culture 1 2 1 1 Yegor Voronin *, Sarah Holte , Julie Overbaugh , Michael Emerman 1 Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America, 2 Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America Abstract Populations of Human Immunodeficiency Virus type 1 (HIV-1) undergo a surprisingly large amount of genetic drift in infected patients despite very large population sizes, which are predicted to be mostly deterministic. Several models have been proposed to explain this phenomenon, but all of them implicitly assume that the process of virus replication itself does not contribute to genetic drift. We developed an assay to measure the amount of genetic drift for HIV populations replicating in cell culture. The assay relies on creation of HIV populations of known size and measurements of variation in frequency of a neutral allele. Using this assay, we show that HIV undergoes approximately ten times more genetic drift than would be expected from its population size, which we defined as the number of infected cells in the culture. We showed that a large portion of the increase in genetic drift is due to non-synchronous infection of target cells. When infections are synchronized, genetic drift for the virus is only 3-fold higher than expected from its population size. Thus, the stochastic nature of biological processes involved in viral replication contributes to increased genetic drift in HIV populations. We propose that appreciation of these effects will allow better understanding of the evolutionary forces acting on HIV in infected patients. Citation: Voronin Y, Holte S