title: SAMHD1 transcript upregulation during SIV infection of the central nervous system does not associate with reduced viral load.
abstract: Restriction of HIV-1 in myeloid-lineage cells is attributed in part to the nucleotidase activity of the SAM-domain and HD-domain containing protein (SAMHD1), which depletes free nucleotides, blocking reverse transcription. In the same cells, the Vpx protein of HIV-2 and most SIVs counteracts SAMHD1. Both Type I and II interferons may stimulate SAMHD1 transcription. The contributions of SAMHD1 to retroviral restriction in the central nervous system (CNS) have been the subject of limited study. We hypothesized that SAMHD1 would respond to interferon in the SIV-infected CNS but would not control virus due to SIV Vpx. Accordingly, we investigated SAMHD1 transcript abundance and association with the Type I interferon response in an SIV model. SAMHD1 transcript levels were IFN responsive, increasing during acute phase infection and decreasing during a more quiescent phase, but generally remaining elevated at all post-infection time points. In vitro, SAMHD1 transcript was abundant in macaque astrocytes and further induced by Type I interferon, while IFN produced a weaker response in the more permissive environment of the macrophage. We cannot rule out a contribution of SAMHD1 to retroviral restriction in relatively non-permissive CNS cell types. We encourage additional research in this area, particularly in the context of HIV-1 infection.
authors.affiliation: Department of Molecular and Comparative Pathobiology, 733 North Broadway, Baltimore, Maryland, 21025, USA.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Buchanan
authors.affiliation: Department of Molecular and Comparative Pathobiology, 733 North Broadway, Baltimore, Maryland, 21025, USA.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Espinoza
authors.affiliation: Department of Molecular and Comparative Pathobiology, 733 North Broadway, Baltimore, Maryland, 21025, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: McAlexander
authors.affiliation: Department of Molecular and Comparative Pathobiology, 733 North Broadway, Baltimore, Maryland, 21025, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Myers
authors.affiliation: Cellular and Molecular Medicine Graduate Program, 733 North Broadway, Baltimore, Maryland, 21025, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Moyer
authors.affiliation: Department of Molecular and Comparative Pathobiology, 733 North Broadway, Baltimore, Maryland, 21025, USA.|Cellular and Molecular Medicine Graduate Program, 733 North Broadway, Baltimore, Maryland, 21025, USA.|Department of Neurology, The Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, Maryland, 21025, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Witwer
mesh_terms: D000818:Animals; D020805:Central Nervous System Viral Diseases / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D005260:Female; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology; D008254:Macaca nemestrina; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D008297:Male; D020559:Monomeric GTP-Binding Proteins / Q000096:biosynthesis / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology*; D019562:Viral Load / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D020559:Monomeric GTP-Binding Proteins