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Virology. 2016 Aug;495:92-100. doi: 10.1016/j.virol.2016.05.002. Epub 2016 May 14.

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

Author information

1
Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA.
2
Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, USA.
3
Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA.
4
Department of Pharmacy, School of Pharmacy, Kyung-Hee University, Seoul, South Korea.
5
Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, USA; Department of Pharmacy, School of Pharmacy, Kyung-Hee University, Seoul, South Korea. Electronic address: baek.kim@emory.edu.
6
Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA. Electronic address: wu.840@osu.edu.

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.

KEYWORDS:

Apoptosis; Cell cycle; Gene knockout; HIV-1; Monocytic cells; Restriction; SAMHD1; dNTP

PMID:
27183329
PMCID:
PMC4912869
DOI:
10.1016/j.virol.2016.05.002
[Indexed for MEDLINE]
Free PMC Article

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