HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase

David C. Goldstone, Valerie Ennis-Adeniran, Joseph J. Hedden, Harriet C T Groom, Gillian I. Rice, Evangelos Christodoulou, Philip A. Walker, Geoff Kelly, Lesley F. Haire, Melvyn W. Yap, Luiz Pedro S De Carvalho, Jonathan P. Stoye, Yanick J. Crow, Ian A. Taylor, Michelle Webb

    Research output: Contribution to journalArticlepeer-review


    SAMHD1, an analogue of the murine interferon (IFN)-Î 3-induced gene Mg11 (ref. 1), has recently been identified as a human immunodeficiency virus-1 (HIV-1) restriction factor that blocks early-stage virus replication in dendritic and other myeloid cells and is the target of the lentiviral protein Vpx, which can relieve HIV-1 restriction. SAMHD1 is also associated with Aicardi-Goutières syndrome (AGS), an inflammatory encephalopathy characterized by chronic cerebrospinal fluid lymphocytosis and elevated levels of the antiviral cytokine IFN-α. The pathology associated with AGS resembles congenital viral infection, such as transplacentally acquired HIV. Here we show that human SAMHD1 is a potent dGTP-stimulated triphosphohydrolase that converts deoxynucleoside triphosphates to the constituent deoxynucleoside and inorganic triphosphate. The crystal structure of the catalytic core of SAMHD1 reveals that the protein is dimeric and indicates a molecular basis for dGTP stimulation of catalytic activity against dNTPs. We propose that SAMHD1, which is highly expressed in dendritic cells, restricts HIV-1 replication by hydrolysing the majority of cellular dNTPs, thus inhibiting reverse transcription and viral complementary DNA (cDNA) synthesis. © 2011 Macmillan Publishers Limited. All rights reserved.
    Original languageEnglish
    Pages (from-to)379-382
    Number of pages3
    Issue number7377
    Publication statusPublished - 15 Dec 2011


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