Imperial College London
Alternate

ProfessorPeterO'Hare

Faculty of Medicine, Department of Infectious Disease

Chair in Virology
 
 
 
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Contact

 

+44 (0)20 7594 9517p.ohare Website

 
 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bodda:2020:10.1084/jem.20191422,
author = {Bodda, C and Reinert, LS and Fruhwürth, S and Richardo, T and Sun, C and Zhang, B-C and Kalamvoki, M and Pohlmann, A and Mogensen, TH and Bergström, P and Agholme, L and O'Hare, P and Sodeik, B and Gyrd-Hansen, M and Zetterberg, H and Paludan, SR},
doi = {10.1084/jem.20191422},
journal = {Journal of Experimental Medicine},
title = {HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection},
url = {http://dx.doi.org/10.1084/jem.20191422},
volume = {217},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Herpes simplex virus (HSV) is the main cause of viral encephalitis in the Western world, and the type I interferon (IFN) system is important for antiviral control in the brain. Here, we have compared Ifnb induction in mixed murine brain cell cultures by a panel of HSV1 mutants, each devoid of one mechanism to counteract the IFN-stimulating cGAS-STING pathway. We found that a mutant lacking the deubiquitinase (DUB) activity of the VP1-2 protein induced particularly strong expression of Ifnb and IFN-stimulated genes. HSV1 ΔDUB also induced elevated IFN expression in murine and human microglia and exhibited reduced viral replication in the brain. This was associated with increased ubiquitination of STING and elevated phosphorylation of STING, TBK1, and IRF3. VP1-2 associated directly with STING, leading to its deubiquitination. Recruitment of VP1-2 to STING was dependent on K150 of STING, which was ubiquitinated by TRIM32. Thus, the DUB activity of HSV1 VP1-2 is a major viral immune-evasion mechanism in the brain.
AU  - Bodda,C
AU  - Reinert,LS
AU  - Fruhwürth,S
AU  - Richardo,T
AU  - Sun,C
AU  - Zhang,B-C
AU  - Kalamvoki,M
AU  - Pohlmann,A
AU  - Mogensen,TH
AU  - Bergström,P
AU  - Agholme,L
AU  - O'Hare,P
AU  - Sodeik,B
AU  - Gyrd-Hansen,M
AU  - Zetterberg,H
AU  - Paludan,SR
DO  - 10.1084/jem.20191422
PY  - 2020///
SN  - 0022-1007
TI  - HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection
T2  - Journal of Experimental Medicine
UR  - http://dx.doi.org/10.1084/jem.20191422
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32383759
UR  - http://hdl.handle.net/10044/1/80645
VL  - 217
ER  -
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