title: SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells.
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.
authors.affiliation: Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA.
authors.forename: Serena
authors.initials: S
authors.lastname: Bonifati
authors.affiliation: Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Michele B
authors.initials: MB
authors.lastname: Daly
authors.affiliation: Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA.
authors.forename: Corine
authors.initials: C
authors.lastname: St Gelais
authors.affiliation: Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Hollenbaugh
authors.affiliation: Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Shepard
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Kennedy
authors.affiliation: Department of Pharmacy, School of Pharmacy, Kyung-Hee University, Seoul, South Korea.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
authors.affiliation: 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.
authors.forename: Baek
authors.initials: B
authors.lastname: Kim
authors.affiliation: Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA. Electronic address: wu.840@osu.edu.
authors.forename: Li
authors.initials: L
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000235:genetics; D015415:Biomarkers; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D055786:Gene Knockout Techniques; D020868:Gene Silencing; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000378:metabolism* / Q000821:virology*; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000076106:SAM Domain and HD Domain-Containing Protein 1
chemical_list: D015415:Biomarkers; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D053148:Caspase 3; D053179:Caspase 7; D020559:Monomeric GTP-Binding Proteins
keywords: Apoptosis; Cell cycle; Gene knockout; HIV-1; Monocytic cells; Restriction; SAMHD1; dNTP