title: SAMHD1 host restriction factor: a link with innate immune sensing of retrovirus infection.
abstract: SAMHD1 [sterile alpha motif and histidine-aspartic domain (HD) containing protein 1] is the most recent addition to a unique group of host restriction factors that limit retroviral replication at distinct stages of the viral life cycle. SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase that degrades the intracellular pool of deoxynucleoside triphosphates available during early reverse transcription. SAMHD1 activity is blocked by the Vpx accessory function present in human immunodeficiency virus type 2 and SIVsm. Mutations in SAMHD1 are associated with the autoimmune disorder Aicardi-Goutières syndrome, thus emphasizing its role in regulation of the immune response. SAMHD1 antiretroviral activity is modulated by post-translational modifications, cell-cycle-dependent functions and cytokine-mediated changes. Innate receptors that sense retroviral DNA intermediates are the focus of intense study, and recent studies have established a link among SAMHD1 restriction, innate sensing of DNA and protective immune responses. Cell-cycle-dependent regulation of SAMHD1 by phosphorylation and the increasingly broad range of viruses inhibited by SAMHD1 further emphasize the importance of these mechanisms of host restriction. This review highlights current knowledge regarding SAMHD1 regulation and its impact on innate immune signaling and retroviral restriction.
authors.affiliation: Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, QC, Canada H3T 1E2.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Sze
authors.forename: David
authors.initials: D
authors.lastname: Olagnier
authors.forename: Rongtuan
authors.initials: R
authors.lastname: Lin
authors.forename: Julien
authors.initials: J
authors.lastname: van Grevenynghe
authors.forename: John
authors.initials: J
authors.lastname: Hiscott
mesh_terms: D020274:Autoimmune Diseases of the Nervous System / Q000235:genetics / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D015498:HIV-2 / Q000276:immunology / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D018448:Models, Immunological; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009421:Nervous System Malformations / Q000235:genetics / Q000276:immunology; D012190:Retroviridae / Q000276:immunology* / Q000502:physiology; D012192:Retroviridae Infections / Q000276:immunology* / Q000821:virology; D000076106:SAM Domain and HD Domain-Containing Protein 1; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000276:immunology
chemical_list: D004279:DNA, Viral; C074286:VPX protein, Human immunodeficiency virus 2; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins
keywords: AGS; Aicardi–Goutières syndrome; CDK1; HIV-1; HTLV-1; MDM; RTI; SAMHD1; cyclin-dependent kinase 1; double-stranded DNA; dsDNA; host restriction; human T cell leukemia virus type 1; human immunodeficiency virus type 1; inflammation; innate immunity; monocyte-derived macrophage; pDC; plasmacytoid dendritic cell; reverse-transcribed intermediate; single-stranded DNA; ssDNA