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Virology. 2016 Jan;487:273-84. doi: 10.1016/j.virol.2015.10.024. Epub 2015 Nov 12.

Phosphorylation of mouse SAMHD1 regulates its restriction of human immunodeficiency virus type 1 infection, but not murine leukemia virus infection.

Author information

1
Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA.
2
ProSci, Inc., 12170 Flint Place, Poway, CA, USA.
3
Department of Pediatrics, Center for Drug Discovery, Emory University School of Medicine, 1760 Haygood Drive, Atlanta, GA, USA.
4
Center for Microbial Interface Biology, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA; Department of Microbial Infection and Immunity, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA.
5
Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA; Center for Microbial Interface Biology, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA; Department of Microbial Infection and Immunity, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA; Comprehensive Cancer Center, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA. Electronic address: wu.840@osu.edu.

Abstract

Human SAMHD1 (hSAMHD1) restricts HIV-1 infection in non-dividing cells by depleting intracellular dNTPs to limit viral reverse transcription. Phosphorylation of hSAMHD1 at threonine (T) 592 by cyclin-dependent kinase (CDK) 1 and CDK2 negatively regulates HIV-1 restriction. Mouse SAMHD1 (mSAMHD1) restricts HIV-1 infection in non-dividing cells, but whether its phosphorylation regulates retroviral restriction is unknown. Here we identified six phospho-sites of mSAMHD1, including T634 that is homologous to T592 of hSAMHD1 and phosphorylated by CDK1 and CDK2. We found that wild-type (WT) mSAMHD1 and a phospho-ablative mutant, but not a phospho-mimetic mutant, restricted HIV-1 infection in differentiated U937 cells. Murine leukemia virus (MLV) infection of dividing NIH3T3 cells was modestly restricted by mSAMHD1 WT and phospho-mutants, but not by a dNTPase-defective mutant. Our results suggest that phosphorylation of mSAMHD1 at T634 by CDK1/2 negatively regulates its HIV-1 restriction in differentiated cells, but does not affect its MLV restriction in dividing cells.

KEYWORDS:

HIV-1; Infection; MLV; Mouse and human SAMHD1; Phosphorylation; Restriction

PMID:
26580513
PMCID:
PMC4679491
DOI:
10.1016/j.virol.2015.10.024
[Indexed for MEDLINE]
Free PMC Article

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