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Roles of SAMHD1 in antiviral defense, autoimmunity and cancer
journal contributionposted on 2023-05-19, 10:14 authored by Li, M, Zhang, D, Zhu, M, Shen, Y, Wei, W, Ying, S, Heinrich KornerHeinrich Korner, Li, J
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.
Publication titleReviews in Medical Virology
Department/SchoolMenzies Institute for Medical Research
PublisherJohn Wiley & Sons Ltd
Place of publicationThe Atrium, Southern Gate, Chichester, England, W Sussex, Po19 8Sq
Rights statementCopyright 2017 John Wiley & Sons, Ltd.