A viral kinase counteracts in vivo restriction of murine cytomegalovirus by SAMHD1

Deutschmann J, Schneider A, Gruska I, Vetter B, Thomas D, Kießling M, Wittmann S, Herrmann A, Schindler M, Milbradt J, Ferreirós N, Winkler T, Wiebusch L, Gramberg T (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Nature Microbiology Nature Research

DOI: 10.1038/s41564-019-0529-z

Abstract

The deoxynucleotide triphosphate (dNTP) hydrolase SAMHD1 inhibits retroviruses in non-dividing myeloid cells. Although antiviral activity towards DNA viruses has also been demonstrated, the role of SAMHD1 during cytomegalovirus (CMV) infection remains unclear. To determine the impact of SAMHD1 on the replication of CMV, we used murine CMV (MCMV) to infect a previously established SAMHD1 knockout mouse model and found that SAMHD1 inhibits the replication of MCMV in vivo. By comparing the replication of MCMV in vitro in myeloid cells and fibroblasts from SAMHD1-knockout and control mice, we found that the viral kinase M97 counteracts SAMHD1 after infection by phosphorylating the regulatory residue threonine 603. The phosphorylation of SAMHD1 in infected cells correlated with a reduced level of dNTP hydrolase activity and the loss of viral restriction. Together, we demonstrate that SAMHD1 acts as a restriction factor in vivo and we identify the M97-mediated phosphorylation of SAMHD1 as a previously undescribed viral countermeasure.

Authors with CRIS profile

Andrea Schneider Lehrstuhl für Genetik Melissa Kießling Lehrstuhl für Genetik Alexandra Herrmann Institute of Clinical and Molecular Virology Jens Milbradt Medizinische Fakultät Thomas Winkler Professur für Genetik Thomas Gramberg Juniorprofessur für Antivirale Native Immunität

Involved external institutions

Charité - Universitätsmedizin Berlin DE Germany (DE) Goethe-Universität Frankfurt am Main DE Germany (DE) Universitätsklinikum Tübingen DE Germany (DE)

How to cite

APA:

Deutschmann, J., Schneider, A., Gruska, I., Vetter, B., Thomas, D., Kießling, M.,... Gramberg, T. (2019). A viral kinase counteracts in vivo restriction of murine cytomegalovirus by SAMHD1. Nature Microbiology. https://dx.doi.org/10.1038/s41564-019-0529-z

MLA:

Deutschmann, Janina, et al. "A viral kinase counteracts in vivo restriction of murine cytomegalovirus by SAMHD1." Nature Microbiology (2019).

BibTeX: Download