title: The human P(k) histo-blood group antigen provides protection against HIV-1 infection.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Lund
authors.forename: Martin L
authors.initials: ML
authors.lastname: Olsson
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ramkumar
authors.forename: Darinka
authors.initials: D
authors.lastname: Sakac
authors.forename: Vered
authors.initials: V
authors.lastname: Yahalom
authors.forename: Cyril
authors.initials: C
authors.lastname: Levene
authors.forename: Asa
authors.initials: A
authors.lastname: Hellberg
authors.forename: Xue-Zhong
authors.initials: XZ
authors.lastname: Ma
authors.forename: Beth
authors.initials: B
authors.lastname: Binnington
authors.forename: Daniel
authors.initials: D
authors.lastname: Jung
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Lingwood
authors.forename: Donald R
authors.initials: DR
authors.lastname: Branch
mesh_terms: 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*
chemical_list: 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