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

Feifei Wang; Corine St. Gelais; Suresh de Silva; Hong Zhang; Yu Geng; Caitlin Shepard; Baek Kim; Jacob S Yount; Li Wu

doi:10.1016/j.virol.2015.10.024

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

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

Feifei Wang, Corine St. Gelais, Suresh de Silva, Hong Zhang, Yu Geng, Caitlin Shepard, Baek Kim, Jacob S Yount and Li Wu

Virology (New York, N.Y.), Vol.487, pp.273-284

01/2016

DOI: 10.1016/j.virol.2015.10.024

PMCID: PMC4679491

PMID: 26580513

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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. •Mouse SAMHD1 (mSAMHD1) restricts HIV-1 infection, but its regulation is unknown.•Six phospho-sites of mSAMHD1 were identified by mass spectrometry.•T634 of mSAMHD1 is phosphorylated by CDK1 and CDK2.•mSAMHD1 restricts MLV infection in dividing cells.•T634 phosphorylation of mSAMHD1 negatively regulates HIV-1, but not MLV restriction.

Phosphorylation

Mouse and human SAMHD1

HIV-1

Infection

Restriction

MLV

Details

Title: Subtitle: Phosphorylation of mouse SAMHD1 regulates its restriction of human immunodeficiency virus type 1 infection, but not murine leukemia virus infection
Creators: Feifei Wang - Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA
Corine St. Gelais - Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA
Suresh de Silva - Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA
Hong Zhang - ProSci, Inc., 12170 Flint Place, Poway, CA, USA
Yu Geng - ProSci, Inc., 12170 Flint Place, Poway, CA, USA
Caitlin Shepard - Department of Pediatrics, Center for Drug Discovery, Emory University School of Medicine, 1760 Haygood Drive, Atlanta, GA, USA
Baek Kim - Department of Pediatrics, Center for Drug Discovery, Emory University School of Medicine, 1760 Haygood Drive, Atlanta, GA, USA
Jacob S Yount - Center for Microbial Interface Biology, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA
Li Wu - Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA
Resource Type: Journal article
Publication Details: Virology (New York, N.Y.), Vol.487, pp.273-284
DOI: 10.1016/j.virol.2015.10.024
PMID: 26580513
PMCID: PMC4679491
NLM abbreviation: Virology
ISSN: 0042-6822
eISSN: 1096-0341
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: AI104483; name: Public Health Preparedness for Infectious Diseases Program of The Ohio State University; DOI: 10.13039/100000002, name: National Institutes of Health, award: CA181997, AI120209; name: C. Glenn Barber Fund from the Ohio State University; DOI: 10.13039/100000002, name: National Institutes of Health, award: AI095348, AI114826; DOI: 10.13039/100000002, name: National Institutes of Health, award: AI049781, GM104198
Language: English
Date published: 01/2016
Academic Unit: Microbiology and Immunology
Record Identifier: 9984002375202771

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