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Roles of SAMHD1 in antiviral defense, autoimmunity and cancer
journal contribution
posted on 2023-05-19, 10:14 authored by Li, M, Zhang, D, Zhu, M, Shen, Y, Wei, W, Ying, S, Heinrich KornerHeinrich Korner, Li, JThe 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.
History
Publication title
Reviews in Medical VirologyVolume
27Issue
4Article number
e1931Number
e1931Pagination
1-12ISSN
1052-9276Department/School
Menzies Institute for Medical ResearchPublisher
John Wiley & Sons LtdPlace of publication
The Atrium, Southern Gate, Chichester, England, W Sussex, Po19 8SqRights statement
Copyright 2017 John Wiley & Sons, Ltd.Repository Status
- Restricted