RGD Reference Report - A viral kinase counteracts in vivo restriction of murine cytomegalovirus by SAMHD1. - Rat Genome Database

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

Authors: Deutschmann, Janina  Schneider, Andrea  Gruska, Iris  Vetter, Barbara  Thomas, Dominique  Kießling, Melissa  Wittmann, Sabine  Herrmann, Alexandra  Schindler, Michael  Milbradt, Jens  Ferreirós, Nerea  Winkler, Thomas H  Wiebusch, Lüder  Gramberg, Thomas 
Citation: Deutschmann J, etal., Nat Microbiol. 2019 Dec;4(12):2273-2284. doi: 10.1038/s41564-019-0529-z. Epub 2019 Sep 23.
RGD ID: 149735526
Pubmed: PMID:31548683   (View Abstract at PubMed)
DOI: DOI:10.1038/s41564-019-0529-z   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SAMHD1HumanCytomegalovirus Infections exacerbatesISOSamhd1 (Mus musculus) RGD 
Samhd1RatCytomegalovirus Infections exacerbatesISOSamhd1 (Mus musculus) RGD 
Samhd1MouseCytomegalovirus Infections exacerbatesIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Samhd1  (SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1)

Genes (Mus musculus)
Samhd1  (SAM domain and HD domain, 1)

Genes (Homo sapiens)
SAMHD1  (SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1)


Additional Information