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

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Author

  • 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
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Summary, in English

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 P-1(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. Pk 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. (Blood. 2009;113:4980-4991)

Publishing year

2009

Language

English

Pages

4980-4991

Publication/Series

Blood

Volume

113

Issue

20

Document type

Journal article

Publisher

American Society of Hematology

Topic

  • Hematology

Status

Published

Research group

  • Transfusion Medicine

ISBN/ISSN/Other

  • ISSN: 1528-0020