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Roles of SAMHD1 in antiviral defense, autoimmunity and cancer

Li, M, Zhang, D, Zhu, M, Shen, Y, Wei, W, Ying, S, Korner, H ORCID: 0000-0003-4610-2814 and Li, J 2017 , 'Roles of SAMHD1 in antiviral defense, autoimmunity and cancer' , Reviews in Medical Virology, vol. 27, no. 4 , pp. 1-12 , doi: 10.1002/rmv.1931.

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Abstract

The enzyme, sterile α motif and histidine-aspartic acid domain-containing protein 1 (SAMHD1) diminishes infection of human immunodeficiency virus type 1 (HIV-1) by hydrolyzing intracellular deoxynucleotide triphosphates (dNTPs) in myeloid cells and resting CD4+ T cells. This dNTP degradation reduces the dNTP concentration to a level insufficient for viral cDNA synthesis, thereby inhibiting retroviral replication. This antiviral enzymatic activity can be inhibited by viral protein X (Vpx). The HIV-2/SIV Vpx causes degradation of SAMHD1, thus interfering with the SAMHD1-mediated restriction of retroviral replication. Recently, SAMHD1 has been suggested to restrict HIV-1 infection by directly digesting genomic HIV-1 RNA through a still controversial RNase activity. Here, we summarize the current knowledge about structure, antiviral mechanisms, intracellular localization, interferon-regulated expression of SAMHD1. We also describe SAMHD1-deficient animal models and an antiviral drug on the basis of disrupting proteasomal degradation of SAMHD1. In addition, the possible roles of SAMHD1 in regulating innate immune sensing, Aicardi-Goutières syndrome and cancer are discussed in this review.

Item Type: Article
Authors/Creators:Li, M and Zhang, D and Zhu, M and Shen, Y and Wei, W and Ying, S and Korner, H and Li, J
Keywords: Aicardi-Goutieres syndrome, SAMHD1, antiviral mechanism, cancer
Journal or Publication Title: Reviews in Medical Virology
Publisher: John Wiley & Sons Ltd
ISSN: 1052-9276
DOI / ID Number: 10.1002/rmv.1931
Copyright Information:

Copyright 2017 John Wiley & Sons, Ltd.

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