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{Barreca:2006,
author = {Barreca, C and O'Hare, P},
journal = {J Virol},
pages = {9171--9180},
title = {Characterization of a potent refractory state and persistence of herpes simplex virus 1 in cell culture},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16940528},
volume = {80},
year = {2006}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Herpes simplex virus (HSV) normally undergoes productive cytocidal infection in culture and is thought of as relatively resistant to innate immune responses such as interferon. We previously described an unusual pattern of infection in culture in MDBK cells, which after initial productive infection, surprisingly resulted in progressive suppression of replication and cell recovery. The dominance of the refractory state was due to the inability to suppress interferon production and subsequent paracrine signaling. Here, using a wild-type HSV-1 strain expressing green fluorescent protein (GFP)-VP16, we analyze aspects of long-term HSV persistence resulting from this oscillating refractory state. We show that the gradual suppression of GFP-VP16 expression correlated with a biphasic pattern of accumulation of viral DNA and extracellular virus titers. We quantify virus maintenance in a minor subpopulation of cells during subculture, show the reemergence of virus by infectious center assay, and demonstrate that this required intracellular events over a 24- to 48-h time course. We also demonstrate that conditioned medium (cMed) from infected cells induced a profound shutoff of HSV gene expression at the transcriptional level. Finally, we demonstrate that this suppression was extremely rapid, requiring only 1 h of treatment to essentially abolish HSV immediate-early expression, and surprisingly persisted for almost 2 days after removal of the cMed. These combined effects underpin the oscillating effect both in plaque progression, where infection spreads but is overwhelmed by the accumulation of inhibitory components, enabling cell recovery, and virus maintenance in a subpopulation of cells. These results may be relevant to consider in studies of HSV latency in different animal models.
AU  - Barreca,C
AU  - O'Hare,P
EP  - 9180
PY  - 2006///
SP  - 9171
TI  - Characterization of a potent refractory state and persistence of herpes simplex virus 1 in cell culture
T2  - J Virol
UR  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16940528
VL  - 80
ER  -
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