The human P^k histo-blood group antigen provides protection against HIV-1 infection

Several human histo-blood groups are glycosphingolipids, including P/P1/P^k. Glycosphingolipids are implicated in HIV-host-cell-fusion and some bind to HIV-gp120 in vitro. Based on our previous studies on Fabry disease, where P^k accumulates and reduces infection, and a soluble P^k analog that inhibits infection, we investigated cell surface-expressed P^k in HIV infection. HIV-1 infection of peripheral blood-derived mononuclear cells (PBMCs) from otherwise healthy persons, with blood group P₁^k, where P^k is overexpressed, or blood group p, that completely lacks P^k, were compared with draw date-matched controls. Fluorescence-activated cell sorter analysis and/or thin layer chromatography were used to verify P^k levels. P ₁^k PBMCs were highly resistant to R5 and X4 HIV-1 infection. In contrast, p PBMCs showed 10- to 1000-fold increased susceptibility to HIV-1 infection. Surface and total cell expression of P^k, but not CD4 or chemokine coreceptor expression, correlated with infection. P ^k liposome-fused cells and CD4⁺ HeLa cells manipulated to express high or low P^k levels confirmed a protective effect of P ^k. We conclude that P^k expression strongly influences susceptibility to HIV-1 infection, which implicates P^k as a new endogenous cell-surface factor that may provide protection against HIV-1 infection.