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 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. 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.
Lund
Nicole
N
Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada.
Olsson
Martin L
ML
Ramkumar
Stephanie
S
Sakac
Darinka
D
Yahalom
Vered
V
Levene
Cyril
C
Hellberg
Asa
A
Ma
Xue-Zhong
XZ
Binnington
Beth
B
Jung
Daniel
D
Lingwood
Clifford A
CA
Branch
Donald R
DR
D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D019610:Cytoprotection / Q000235:genetics / Q000276:immunology*; D005700:Galactosyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000097:blood* / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D019169:Jurkat Cells; D034741:RNA, Small Interfering / Q000494:pharmacology; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D014162:Transfection; D014281:Trihexosylceramides / Q000378:metabolism / Q000502:physiology*
D015704:CD4 Antigens; C527276:CXCR4 protein, human; D034741:RNA, Small Interfering; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D005700:Galactosyltransferases; C410407:UDP-galactose - Galbeta1-4Glcbeta1-Cer alpha1,4-galactosyltransferase