Phosphorylation of murine SAMHD1 regulates its antiretroviral activity

Wittmann S, Behrendt R, Eißmann K, Volkmann B, Thomas D, Ebert T, Cribier A, Benkirane M, Hornung V, Bouzas NF, Gramberg T (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Retrovirology BioMed Central

Book Volume: 12

Pages Range: 103

Journal Issue: 1

DOI: 10.1186/s12977-015-0229-6

Abstract

Human SAMHD1 is a triphosphohydrolase that restricts the replication of retroviruses, retroelements and DNA viruses in noncycling cells. While modes of action have been extensively described for human SAMHD1, only little is known about the regulation of SAMHD1 in the mouse. Here, we characterize the antiviral activity of murine SAMHD1 with the help of knockout mice to shed light on the regulation and the mechanism of the SAMHD1 restriction and to validate the SAMHD1 knockout mouse model for the use in future infectivity studies.We found that endogenous mouse SAMHD1 restricts not only HIV-1 but also MLV reporter virus infection at the level of reverse transcription in primary myeloid cells. Similar to the human protein, the antiviral activity of murine SAMHD1 is regulated through phosphorylation at threonine 603 and is limited to nondividing cells. Comparing the susceptibility to infection with intracellular dNTP levels and SAMHD1 phosphorylation in different cell types shows that both functions are important determinants of the antiviral activity of murine SAMHD1. In contrast, we found the proposed RNase activity of SAMHD1 to be less important and could not detect any effect of mouse or human SAMHD1 on the level of incoming viral RNA.Our findings show that SAMHD1 in the mouse blocks retroviral infection at the level of reverse transcription and is regulated through cell cycle-dependent phosphorylation. We show that the antiviral restriction mediated by murine SAMHD1 is mechanistically similar to what is known for the human protein, making the SAMHD1 knockout mouse model a valuable tool to characterize the influence of SAMHD1 on the replication of different viruses in vivo.

Authors with CRIS profile

Kristin Eißmann Institute of Clinical and Molecular Virology Bianca Volkmann Institute of Clinical and Molecular Virology Thomas Gramberg Institute of Clinical and Molecular Virology

Involved external institutions

Goethe-Universität Frankfurt am Main DE Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) National Center for Scientific Research / Centre national de la recherche scientifique (CNRS) FR France (FR) Technische Universität Dresden DE Germany (DE)

How to cite

APA:

Wittmann, S., Behrendt, R., Eißmann, K., Volkmann, B., Thomas, D., Ebert, T.,... Gramberg, T. (2015). Phosphorylation of murine SAMHD1 regulates its antiretroviral activity. Retrovirology, 12(1), 103. https://doi.org/10.1186/s12977-015-0229-6

MLA:

Wittmann, Sabine, et al. "Phosphorylation of murine SAMHD1 regulates its antiretroviral activity." Retrovirology 12.1 (2015): 103.

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