Journal article
SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells
Virology (New York, N.Y.), Vol.495, pp.92-100
08/2016
DOI: 10.1016/j.virol.2016.05.002
PMCID: PMC4912869
PMID: 27183329
Abstract
SAMHD1 limits HIV-1 infection in non-dividing myeloid cells by decreasing intracellular dNTP pools. HIV-1 restriction by SAMHD1 in these cells likely prevents activation of antiviral immune responses and modulates viral pathogenesis, thus highlighting a critical role of SAMHD1 in HIV-1 physiopathology. Here, we explored the function of SAMHD1 in regulating cell proliferation, cell cycle progression and apoptosis in monocytic THP-1 cells. Using the CRISPR/Cas9 technology, we generated THP-1 cells with stable SAMHD1 knockout. We found that silencing of SAMHD1 in cycling cells stimulates cell proliferation, redistributes cell cycle population in the G1/G0 phase and reduces apoptosis. These alterations correlated with increased dNTP levels and more efficient HIV-1 infection in dividing SAMHD1 knockout cells relative to control. Our results suggest that SAMHD1, through its dNTPase activity, affects cell proliferation, cell cycle distribution and apoptosis, and emphasize a key role of SAMHD1 in the interplay between cell cycle regulation and HIV-1 infection.
Details
- Title: Subtitle
- SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells
- Creators
- Serena Bonifati - Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USAMichele B Daly - Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, USACorine St. Gelais - Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USASun Hee Kim - Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USAJoseph A Hollenbaugh - Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, USACaitlin Shepard - Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, USAEdward M Kennedy - Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USADong.-Hyun Kim - Department of Pharmacy, School of Pharmacy, Kyung-Hee University, Seoul, South KoreaRaymond F Schinazi - Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, USABaek Kim - Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, USALi Wu - Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA
- Resource Type
- Journal article
- Publication Details
- Virology (New York, N.Y.), Vol.495, pp.92-100
- DOI
- 10.1016/j.virol.2016.05.002
- PMID
- 27183329
- PMCID
- PMC4912869
- NLM abbreviation
- Virology
- ISSN
- 0042-6822
- eISSN
- 1096-0341
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000002, name: NIH, award: AI104483, AI049781, GM104198, MH100999, CA181997 and AI120209; name: Emory+Children's Pediatric Research Center Flow Cytometry Core; name: Emory University Integrated Cellular Imaging Microscopy Core of the Emory+Children’s Pediatric Research Center; name: Public Health Preparedness for Infectious Diseases Program of The Ohio State University
- Language
- English
- Date published
- 08/2016
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984001222102771
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