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Restricting HIV the SAMHD1 way: through nucleotide starvation

Institut Pasteur, Unité Virus et Immunité, Département de Virologie, Centre National de la Recherche Scientifique, Unité de Recherche Associée 3015, 28 rue du Docteur Roux, F-75015 Paris, France.
Nature Reviews Microbiology (Impact Factor: 23.32). 08/2012; 10(10):675-80. DOI: 10.1038/nrmicro2862
Source: PubMed

ABSTRACT HIV replication is limited by cellular restriction factors, such as APOBEC and tetherin, which themselves are counteracted by viral proteins. SAMHD1 was recently identified as a novel HIV restriction factor in myeloid cells, and was shown to be blocked by the lentiviral protein Vpx. SAMHD1 limits viral replication through an original mechanism: it hydrolyses intracellular dNTPs in non-cycling cells, thus decreasing the amount of these key substrates, which are required for viral DNA synthesis. In this Progress article, we describe how SAMHD1 regulates the pool of intracellular nucleotides to control HIV replication and the innate immune response.

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    • "The deoxynucleoside triphosphate triphosphohydrolase function of SAMHD1 blocks reverse transcription of retroviral RNA by depleting the dNTP pool required for complete reverse transcription (Ayinde et al., 2012; Goldstone et al., 2011; Hollenbaugh et al., 2013; Kim et al., 2012; Lahouassa et al., 2012), an effect reversed by the addition of exogenous dN (Lahouassa et al., 2012). To explore the relationship between the triphosphohydrolase activity of SAMHD1 and apoptosis, primary monocytes were infected with HTLV-1 in the presence of increasing concentrations of exogenous dN (0–100 nM). "
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    • "Moreover, monocytes and resting T cells from SAMHD1-deficient individuals more efficiently support HIV-1 replication (Berger et al, 2011; Baldauf et al, 2012; Descours et al, 2012). Collectively, these in vitro observations define SAMHD1 as a host restriction factor for HIV-1 in cultured human cells (Ayinde et al, 2012). SAMHD1 deficiency in humans results in Aicardi-Goutières syndrome (AGS), a hereditary autoimmune encephalopathy that mimics congenital virus infection and is characterized by type I interferon (IFN) production (Crow and Livingston, 2008; Rice et al, 2009). "
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