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{Mohnke:2021:10.1101/2021.01.29.428770,
author = {Mohnke, J and Stark, I and Fischer, M and Grothey, A and OHare, P and Sodeik, B and Erhard, F and Dölken, L and Hennig, T},
doi = {10.1101/2021.01.29.428770},
title = {pUL36 de-ubiquitinase activity augments both the initiation and progression of lytic virus infection in IFN–primed cells},
url = {http://dx.doi.org/10.1101/2021.01.29.428770},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:p>The conserved, structural HSV-1 tegument protein pUL36 is essential for both virus entry and assembly. While its N-terminal de-ubiquitinase (DUB) activity is dispensable for infection in cell culture, it is required for efficient virus spread <jats:italic>in vivo</jats:italic> by acting as a potent viral immune evasin. Here, we show that the pUL36 DUB activity was required to overcome interferon-(IFN)-mediated suppression of both plaque initiation and progression to productive infection. Immediately upon virus entry, incoming tegument-derived pUL36-DUB activity helped the virus to escape intrinsic antiviral resistance and efficiently initiate lytic virus replication in IFN-primed cells. Subsequently, <jats:italic>de novo</jats:italic> expressed pUL36-DUB augmented the efficiency of productive infection and virus yield. Interestingly, removal of IFN shortly after inoculation only resulted in a partial rescue of plaque formation, indicating that an IFN-induced defense mechanism eliminates invading virus particles unless counteracted by pUL36-DUB activity. Taken together, we demonstrated that the pUL36 DUB disarms IFN-induced antiviral responses at two levels, namely, to protect the infectivity of invading virus as well as to augment productive virus replication in IFN-primed cells.</jats:p><jats:sec><jats:title>Author Summary</jats:title><jats:p>HSV-1 is an ubiquitous human pathogen that is responsible for common cold sores but may also cause life-threatening disease. pUL36 is an essential and conserved protein of infectious herpesvirus virions with a unique de-ubiquitinating (DUB) activity. The pUL36 DUB is dispensable for efficient virus infection in cell culture but represents an important viral immune evasin <jats:italic>in vivo</jats:italic>. Here, we showed that tegument-derived DUB activity delivered by the invading virus particles is req
AU  - Mohnke,J
AU  - Stark,I
AU  - Fischer,M
AU  - Grothey,A
AU  - OHare,P
AU  - Sodeik,B
AU  - Erhard,F
AU  - Dölken,L
AU  - Hennig,T
DO  - 10.1101/2021.01.29.428770
PY  - 2021///
TI  - pUL36 de-ubiquitinase activity augments both the initiation and progression of lytic virus infection in IFN–primed cells
UR  - http://dx.doi.org/10.1101/2021.01.29.428770
ER  -
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