Abstract

APOBEC3G/CEM15 (hA3G) is a novel host factor that confers resistance to lentiviral infection under experimental conditions. Human immunodeficiency virus (HIV) type 1, however, produces viral infectivity factor (Vif) that targets hA3G for proteolysis, thereby escaping this defense system. To examine hA3G's contribution to the protection against HIV disease progression in humans, we quantified hA3G mRNA levels in peripheral blood mononuclear cells from 6 HIV-uninfected and 25 HIV-infected subjects; the latter group included 8 long-term nonprogressors (LTNPs) and 17 progressors. None of the HIV-infected subjects were receiving antiretroviral therapy. We found a striking inverse correlation between hA3G mRNA levels and HIV viral loads (P < or = 0.00009) and a highly significant positive correlation between hA3G mRNA levels and CD4 cell counts (P < or = 0.00012) in these patients. Furthermore, we discovered that the order of hA3G mRNA levels is LTNPs > HIV-uninfected subjects > progressors.