The human Pk histo-blood group antigen provides protection against HIV-1 infection

Nicole Lund, Martin L. Olsson, Stephanie Ramkumar, Darinka Sakac, Vered Yahalom, Cyril Levene, Åsa Hellberg, Xue Zhong Ma, Beth Binnington, Daniel Jung, Clifford A. Lingwood, Donald R. Branch

Research output: Contribution to journalArticlepeer-review

Abstract

Several human histo-blood groups are glycosphingolipids, including P/P1/Pk. 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 Pk accumulates and reduces infection, and a soluble Pk analog that inhibits infection, we investigated cell surface-expressed Pk in HIV infection. HIV-1 infection of peripheral blood-derived mononuclear cells (PBMCs) from otherwise healthy persons, with blood group P1k, where Pk is overexpressed, or blood group p, that completely lacks Pk, were compared with draw date-matched controls. Fluorescence-activated cell sorter analysis and/or thin layer chromatography were used to verify Pk levels. P 1k 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 Pk, 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 Pk levels confirmed a protective effect of P k. We conclude that Pk expression strongly influences susceptibility to HIV-1 infection, which implicates Pk as a new endogenous cell-surface factor that may provide protection against HIV-1 infection.

Original languageEnglish
Pages (from-to)4980-4991
Number of pages12
JournalBlood
Volume113
Issue number20
DOIs
StatePublished - 2009
Externally publishedYes

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