SAMHD1 transcript upregulation during SIV infection of the central nervous system does not associate with reduced viral load
Year: 2016
Type: article
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.
Source: Scientific Reports
DOI: 10.1038/srep22629
Institutions: Johns Hopkins University, Johns Hopkins Medicine
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: Johns Hopkins University, National Institutes of Health, Center for AIDS Research, University of Washington, Center for AIDS Research, Johns Hopkins University, National Institute of Mental Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Center for Research Resources, Office of Research Infrastructure Programs, National Institutes of Health
Awards: Circulating Cellular and Extracellular Noncoding RNAs in HIV-1 Elite Suppression, G1788611950, G5933640408, G7752999789, Development of an SPF Macaca nemestrina Breeding Colony, Cellular and Molecular Medicine, G9000121584, G9000258633, The Johns Hopkins Center for AIDS Research (JHU CFAR), Continued support for an SPF Macaca nemestrina breeding colony to provide animals to NIH funded HIV research projects, JHU Center for the Advancement of HIV Neurotherapeutics (JHU CAHN)
OpenAlex ID: W2316859883