Title |
HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase
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Published in |
Nature, November 2011
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DOI | 10.1038/nature10623 |
Pubmed ID | |
Authors |
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 |
Abstract |
SAMHD1, an analogue of the murine interferon (IFN)-γ-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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Japan | 2 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Practitioners (doctors, other healthcare professionals) | 1 | 50% |
Members of the public | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 6 | 1% |
United Kingdom | 2 | <1% |
Canada | 2 | <1% |
Norway | 1 | <1% |
India | 1 | <1% |
France | 1 | <1% |
Germany | 1 | <1% |
Switzerland | 1 | <1% |
Spain | 1 | <1% |
Other | 1 | <1% |
Unknown | 456 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 121 | 26% |
Researcher | 89 | 19% |
Student > Master | 52 | 11% |
Student > Bachelor | 43 | 9% |
Student > Doctoral Student | 24 | 5% |
Other | 70 | 15% |
Unknown | 74 | 16% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 169 | 36% |
Biochemistry, Genetics and Molecular Biology | 99 | 21% |
Immunology and Microbiology | 52 | 11% |
Medicine and Dentistry | 47 | 10% |
Chemistry | 8 | 2% |
Other | 21 | 4% |
Unknown | 77 | 16% |