SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells

Journal Article · Mon Aug 15 00:00:00 EDT 2016 · Virology

DOI:https://doi.org/10.1016/J.VIROL.2016.05.002· OSTI ID:22581698

Bonifati, Serena ^[1]; Daly, Michele B. ^[2]; St Gelais, Corine; Kim, Sun Hee ^[1]; Hollenbaugh, Joseph A.; Shepard, Caitlin ^[2]; Kennedy, Edward M. ^[3]; Kim, Dong-Hyun ^[4]; Schinazi, Raymond F. ^[2]; Kim, Baek ^[2]; Wu, Li ^[1]

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1. Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH (United States)
2. Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA (United States)
3. Department of Molecular Genetics and Microbiology, Duke University, Durham, NC (United States)
4. Department of Pharmacy, School of Pharmacy, Kyung-Hee University, Seoul (Korea, Republic of)

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 G{sub 1}/G{sub 0} 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.

• OSTI ID: 22581698
• Journal Information: Virology, Vol. 495; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AIDS VIRUS
APOPTOSIS
CELL CYCLE
CELL PROLIFERATION
GENE REGULATION
KNOCK-OUT REACTIONS
PATHOGENESIS