Host genetic variation and susceptibility to primate lentiviruses

The human immunodeficiency viruses HIV-1 and HIV-2 arose by cross-species transmission of lentiviruses into the human population from nonhuman, old world primates. Despite the rapid, world-wide spread of the HIV/AIDS epidemic, it is clear that individual humans display a high degree of variability in susceptibility to infection and disease progression. Similarly, macaque isolates of simian immunodeficiency virus (SIVmac) arose initially by accidental cross-species transmission from an African monkey species into an Asian species, and experimental infection of Asian macaques, even with clonal SIV isolates, results in a broad range of outcomes. In Africa, more than two-dozen primate species are endemically infected with simian immunodeficiency viruses. Unlike humans and Asian macaques, infection in these natural hosts rarely results in pathogenic outcome. Host genetic variation manifests at multiple levels, influencing both the movement of lentiviruses between species and giving rise to variation in susceptibility to infection, rates of disease progression and severity of pathogenesis within species. Cataloging and understanding host genetic variation has the potential to impact HIV/AIDS research in several areas, including identification of new therapeutic regimens, improved animal models and better interpretation of results from clinical trials.