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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 (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 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 Citing Articles via Google Scholar Google Scholar Articles by Lund, N. Articles by Branch, D. R. Search for Related Content PubMed PubMed Citation Articles by Lund, N. Articles by Branch, D. R. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 14, 2008 Accepted December 11, 2008 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, Asa Hellberg, Xue-Zhong Ma, Beth Binnington, Daniel Jung, Clifford A. Lingwood, and Donald R. Branch* Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University & University Hospital Blood Centre, Lund, Sweden Canadian Blood Services, Toronto, Canada Magen David Adom National Blood Services, Ramat Gan, Israel Department of Medicine, University of Toronto, Toronto, Canada Reseach Institute, Hospital for Sick Children, Toronto, Canada Hema-Quebec Research & Development, Quebec, Canada Department of Biochemistry, University of Toronto, Toronto, Canada Division of Cell and Molecular Biology, Toronto General Research Institute of the University Health Network, Toronto, Canada * Corresponding author; email: don.branch{at}utoronto.ca. Several human histo-blood groups are glycosphingolipids (GSLs), including P/P1/Pk. GSLs are implicated in HIV-host-cell-fusion and several bind to HIV-gp120 in vitro. Based on our previous studies on Fabry disease, where Pk accumulates and reduces infection, and a soluble Pk-analogue 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 individuals, with blood group P1k, where Pk is over-expressed, or blood group p, that completely lack Pk, were compared to draw-date-matched controls. FACS analysis and/or TLC 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 co-receptor 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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