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

Nat Microbiol 2019 12 23;4(12):2273-2284. Epub 2019 Sep 23.

Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41564-019-0529-zDOI Listing
December 2019
2 Reads

Publication Analysis

Top Keywords

samhd1
10
replication mcmv
8
samhd1 inhibits
8
dntp hydrolase
8
phosphorylation samhd1
8
viral kinase
8
myeloid cells
8
demonstrate samhd1
4
mouse model
4
model samhd1
4
mcmv vivo
4
comparing replication
4
vivo comparing
4
restriction demonstrate
4
knockout mouse
4
inhibits replication
4
established samhd1
4
cmv murine
4
murine cmv
4
replication cmv
4

References

(Supplied by CrossRef)

E Franzolin et al.
Proc. Natl Acad. Sci. USA 2013

DC Goldstone et al.
Nature 2011

RD Powell et al.
J. Biol. Chem. 2011

K Hrecka et al.
Nature 2011

N Laguette et al.
Nature 2011

T Gramberg et al.
Retrovirology 2013

ET Kim et al.
J. Virol. 2013

JA Hollenbaugh et al.
PLoS Pathog. 2013

H Lahouassa et al.
Nat. Immunol. 2012

A Cribier et al.
Cell Rep. 2013

TE White et al.
Cell Host Microbe 2013

Similar Publications