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Restricting HIV the SAMHD1 way: through nucleotide starvation

Nature Reviews Microbiology volume 10, pages 675–680 (2012)Cite this article

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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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Figure 1: Effect of SAMHD1, and of other cellular enzymes that target nucleic acids, on HIV-1 replication.

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Acknowledgements

The authors thank members of the Unité Virus et Immunité, Institut Pasteur, Paris, France, for discussions and P. Lebon for critical reading of the manuscript. Work in the authors' laboratory is supported by grants from the French Agence Nationale de Recherche sur le SIDA et les Hépatite Virales (ANRS), SIDACTION, AREVA, the Vaccine Research Institute (Creteil, France), the Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (IBEID) programme and the Institut Pasteur.

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  1. Département de Virologie, Diana Ayinde, Nicoletta Casartelli and Olivier Schwartz are at the Institut Pasteur, Unité Virus et Immunité, Centre National de la Recherche Scientifique, Unité de Recherche Associée 3015, 28 rue du Docteur Roux, F-75015 Paris, France.,

    Diana Ayinde, Nicoletta Casartelli & Olivier Schwartz

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Ayinde, D., Casartelli, N. & Schwartz, O. Restricting HIV the SAMHD1 way: through nucleotide starvation. Nat Rev Microbiol 10, 675–680 (2012). https://doi.org/10.1038/nrmicro2862

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