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Author Notes:

Corresponding author. Center for Retrovirus Research, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA. Phone: 614 292 5408. Li Wu: wu.940@osu.edu

Corresponding author. Center for Drug Discovery, Emory University, Health Science Research Building E432, 1760 Haygood Drive, Atlanta, GA 30322, USA. Phone: 404 727 1454. Baek Kim: baek.kim@emory.edu

Subjects:

Research Funding:

This work was supported by NIH grants AI104483 (L.W.), AI049781 (B.K.), GM104198 (B.K.), and MH100999 (R.F.S.).

This project was supported in part by the Emory+Children’s Pediatric Research Center Flow Cytometry Core and the Emory University Integrated Cellular Imaging Microscopy Core of the Emory+Children’s Pediatric Research Center.

L.W. is also supported in part by the Public Health Preparedness for Infectious Diseases Program of The Ohio State University and by NIH grants (CA181997 and AI120209).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Virology
  • SAMHD1
  • Monocytic cells
  • Gene knockout
  • HIV-1
  • dNTP
  • Restriction
  • Cell cycle
  • Apoptosis
  • IMMUNODEFICIENCY-VIRUS TYPE-1
  • AICARDI-GOUTIERES SYNDROME
  • RESTRICTION FACTOR SAMHD1
  • CD4(+) T-CELLS
  • DENDRITIC CELLS
  • DNTP LEVELS
  • PROTEIN
  • VPX
  • PHOSPHORYLATION
  • LYMPHOCYTES

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

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Journal Title:

Virology

Volume:

Volume 495

Publisher:

, Pages 92-100

Type of Work:

Article | Post-print: After Peer Review

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 G 1 /G 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.

Copyright information:

© 2016 Elsevier Inc..

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