Journal article
ICP0 antagonizes ICP4-dependent silencing of the herpes simplex virus ICP0 gene
PloS one, Vol.5(1), pp.e8837-e8837
01/21/2010
Handle:
https://hdl.handle.net/2376/109035
PMCID: PMC2809113
PMID: 20098619
Abstract
ICP0 is a regulatory protein that plays a critical role in the replication-latency balance of herpes simplex virus (HSV). Absence of ICP0 renders HSV prone to establish quiescent infections, and thus cellular repressor(s) are believed to silence HSV mRNA synthesis when ICP0 fails to accumulate. To date, an ICP0-antagonized repressor has not been identified that restricts HSV mRNA synthesis by more than 2-fold. We report the unexpected discovery that HSV's major transcriptional regulator, ICP4, meets the criteria of a bona fide ICP0-antagonized repressor of viral mRNA synthesis. Our study began when we noted a repressive activity that restricted ICP0 mRNA synthesis by up to 30-fold in the absence of ICP0. When ICP0 accumulated, the repressor only restricted ICP0 mRNA synthesis by 3-fold. ICP4 proved to be necessary and sufficient to repress ICP0 mRNA synthesis, and did so in an ICP4-binding-site-dependent manner. ICP4 co-immunoprecipitated with FLAG-tagged ICP0; thus, a physical interaction likely explains how ICP0 antagonizes ICP4's capacity to silence the ICP0 gene. These findings suggest that ICP0 mRNA synthesis is differentially regulated in HSV-infected cells by the virus-encoded repressor activity embedded in ICP4, and a virus-encoded antirepressor, ICP0. Bacteriophage lambda relies on a similar repression-antirepression regulatory scheme to "decide" whether a given infection will be productive or silent. Therefore, our findings appear to add to the growing list of inexplicable similarities that point to a common evolutionary ancestry between the herpesviruses and tailed bacteriophage.
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Details
- Title
- ICP0 antagonizes ICP4-dependent silencing of the herpes simplex virus ICP0 gene
- Creators
- Mingyu Liu - Department of Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, Illinois, United States of AmericaBrandon RakowskiEdward GershburgCarla M WeisendOlivier LucasEdward E SchmidtWilliam P Halford
- Publication Details
- PloS one, Vol.5(1), pp.e8837-e8837
- Academic Unit
- UNKNOWN
- Publisher
- United States
- Grant note
- R21 AI081072-01A1 / NIAID NIH HHS R21 AI081072 / NIAID NIH HHS R01 AI051414 / NIAID NIH HHS R01 AI51414 / NIAID NIH HHS
- Identifiers
- 99900547312601842
- Language
- English
- Resource Type
- Journal article