title: SAMHD1: at the crossroads of cell proliferation, immune responses, and virus restriction.
abstract: SAMHD1 is a triphosphohydrolase enzyme that controls the intracellular level of deoxyribonucleoside triphosphates (dNTPs) and plays a role in innate immune sensing and autoimmune disease. SAMHD1 has also been identified as an intrinsic virus restriction factor, inactivated through degradation by HIV-2 Vpx or through a post-transcriptional regulatory mechanism. Phosphorylation of SAMHD1 by cyclin-dependent kinases has been strongly associated with inactivation of the virus restriction mechanism, providing an association between virus replication and cell proliferation. Tight regulation of cell proliferation suggests that viruses, particularly HIV-1 replication, latency, and reactivation, may be similarly controlled by multiple checkpoint mechanisms that, in turn, regulate dNTP levels. In this review, we discuss how SAMHD1 is a viral restriction factor, the mechanism associated with viral restriction, the pathway leading to its inactivation in proliferating cells, and how strategies aimed at controlling virus restriction could lead to a functional cure for HIV.
authors.affiliation: AIDS Research Institute-IrsiCaixa and Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Ballana
authors.affiliation: AIDS Research Institute-IrsiCaixa and Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Spain. Electronic address: jaeste@irsicaixa.es.
authors.forename: José A
authors.initials: JA
authors.lastname: Esté
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002478:Cells, Cultured; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D015498:HIV-2 / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D010766:Phosphorylation; D000076106:SAM Domain and HD Domain-Containing Protein 1; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism
chemical_list: C074286:VPX protein, Human immunodeficiency virus 2; 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: HIV; autoimmune disease; cell cycle; innate immunity; restriction factor