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Blood, 14 May 2009, Vol. 113, No. 20, pp. 4980-4991. Prepublished online as a Blood First Edition Paper on January 12, 2009; DOI 10.1182/blood-2008-03-143396. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-03-143396v1 113/20/4980    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Lund, N. Articles by Branch, D. R. PubMed PubMed Citation Articles by Lund, N. Articles by Branch, D. R. Related Collections Immunobiology Transfusion Medicine Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSFUSION MEDICINE The human Pk histo-blood group antigen provides protection against HIV-1 infection Nicole Lund1,2, Martin L. Olsson3, Stephanie Ramkumar1, Darinka Sakac2, Vered Yahalom4, Cyril Levene4, Åsa Hellberg3, Xue-Zhong Ma5,6, Beth Binnington7, Daniel Jung8,9, Clifford A. Lingwood1,7,10, and Donald R. Branch1,2,5,6 1 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON; 2 Canadian Blood Services, Toronto, ON; 3 Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University & University Hospital Blood Centre, Lund, Sweden; 4 Magen David Adom National Blood Services, Ramat Gan, Israel; 5 Department of Medicine, University of Toronto, Toronto, ON; 6 Division of Cell and Molecular Biology, Toronto General Research Institute of the University Health Network, Toronto, ON; 7 Research Institute, Hospital for Sick Children, Toronto, ON; 8 Héma-Québec Research & Development, Québec, QC; 9 Department of Microbiology and Biochemistry, Laval University, Québec, QC; and 10 Department of Biochemistry, University of Toronto, Toronto, ON 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. P1k 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. Pk liposome–fused cells and CD4+ HeLa cells manipulated to express high or low Pk levels confirmed a protective effect of Pk. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A new role for Pk: finding the 1 in a million Christopher D. Hillyer Blood 2009 113: 4826-4827. [Full Text] [PDF] This article has been cited by other articles: C. D. Hillyer A new role for Pk: finding the 1 in a million Blood, May 14, 2009; 113(20): 4826 - 4827. [Full Text] [PDF]

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