Identification of cellular proteins interacting with the retroviral restriction Factor SAMHD1

Corine St. Gelais, Suresh de Silva, Jocelyn C. Hach, Tommy E. White, Felipe Diaz-Griffero, Jacob S. Yount, Li Wu

Research output: Contribution to journalArticle

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Abstract

Human and mouse SAMHD1 proteins block human immunodeficiency virus type 1 (HIV-1) infection in noncycling human monocytic cells by reducing the intracellular deoxynucleoside triphosphate (dNTP) concentrations. Phosphorylation of human SAMHD1 at threonine 592 (T592) by cyclin-dependent kinase 1 (CDK1) and cyclin A2 impairs its HIV-1 restriction activity, but not the dNTP hydrolase activity, suggesting that dNTP depletion is not the sole mechanism of SAMHD1-mediated HIV-1 restriction. Using coimmunoprecipitation and mass spectrometry, we identified and validated two additional host proteins interacting with human SAMHD1, namely, cyclin-dependent kinase 2 (CDK2) and S-phase kinase-associated protein 2 (SKP2). We observed that mouse SAMHD1 specifically interacted with cyclin A2, cyclin B1, CDK1, and CDK2. Given the role of these SAMHD1-interacting proteins in cell cycle progression, we investigated the regulation of these host proteins by monocyte differentiation and activation of CD4+ T cells and examined their effect on the phosphorylation of human SAMHD1 at T592. Our results indicate that primary monocyte differentiation and CD4+ T-cell activation regulate the expression of these SAMHD1-interacting proteins. Furthermore, our results suggest that, in addition to CDK1 and cyclin A2, CDK2 phosphorylates T592 of human SAMHD1 and thereby regulates its HIV-1 restriction function.

Original languageEnglish (US)
Pages (from-to)5834-5844
Number of pages11
JournalJournal of Virology
Volume88
Issue number10
DOIs
StatePublished - 2014

Fingerprint

cyclin-dependent kinase
Cyclin A2
CDC2 Protein Kinase
Cyclin-Dependent Kinase 2
cyclins
HIV-1
Human immunodeficiency virus 1
Threonine
threonine
Proteins
proteins
Monocytes
S-Phase Kinase-Associated Proteins
monocytes
Phosphorylation
phosphorylation
Cyclin B1
T-Lymphocytes
T-lymphocytes
Cell Cycle Proteins

ASJC Scopus subject areas

  • Immunology
  • Virology

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Identification of cellular proteins interacting with the retroviral restriction Factor SAMHD1. / St. Gelais, Corine; de Silva, Suresh; Hach, Jocelyn C.; White, Tommy E.; Diaz-Griffero, Felipe; Yount, Jacob S.; Wu, Li.

In: Journal of Virology, Vol. 88, No. 10, 2014, p. 5834-5844.

Research output: Contribution to journalArticle

St. Gelais, C, de Silva, S, Hach, JC, White, TE, Diaz-Griffero, F, Yount, JS & Wu, L 2014, 'Identification of cellular proteins interacting with the retroviral restriction Factor SAMHD1', Journal of Virology, vol. 88, no. 10, pp. 5834-5844. https://doi.org/10.1128/JVI.00155-14
St. Gelais, Corine ; de Silva, Suresh ; Hach, Jocelyn C. ; White, Tommy E. ; Diaz-Griffero, Felipe ; Yount, Jacob S. ; Wu, Li. / Identification of cellular proteins interacting with the retroviral restriction Factor SAMHD1. In: Journal of Virology. 2014 ; Vol. 88, No. 10. pp. 5834-5844.
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