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HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase.

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.

journal_name

Nature

journal_title

Nature

authors

Goldstone DC,Ennis-Adeniran V,Hedden JJ,Groom HC,Rice GI,Christodoulou E,Walker PA,Kelly G,Haire LF,Yap MW,de Carvalho LP,Stoye JP,Crow YJ,Taylor IA,Webb M

doi

10.1038/nature10623

subject

Has Abstract

pub_date

2011-11-06 00:00:00

pages

379-82

issue

7377

eissn

0028-0836

issn

1476-4687

pii

nature10623

journal_volume

480

pub_type

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