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PMID: 15452220 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Major human cytomegalovirus structural protein pp65 (ppUL83) prevents interferon response factor 3 activation in the interferon response.

Journal of virology ·Vol. 78 ·No. 20 ·2004-10-00 ·Pages 10995-1006

Abate DA, Watanabe S, Mocarski ES

Abstract

We have identified a cytomegalovirus virion protein capable of modulating the rapid induction of an interferon-like response in cells that follows virus binding and penetration. Functional genomics revealed a role for the major cytomegalovirus structural protein, pp65 (ppUL83), in counteracting this response. The underlying mechanism involves a differential impact of this structural protein on the regulation of interferon response factor 3 (IRF-3). In contrast, NF-kappaB is activated independent of pp65, and neither STAT1 nor STAT3 becomes activated by either virus. pp65 is sufficient to prevent the activation of IRF-3 when introduced alone into cells. pp65 acts by inhibiting nuclear accumulation of IRF-3 and is associated with a reduced IRF-3 phosphorylation state. Thus, this investigation shows that the major structural protein of cytomegalovirus is committed to the modulation of the IRF-3 response, a primary mediator of the type I interferon response. By subverting IRF-3, the virus escapes throwing a central alarm devoted to both immediate antiviral control and regulation of the immune response.

MeSH Terms
Cells, Cultured Cytomegalovirus/genetics,pathogenicity DNA-Binding Proteins/metabolism Fibroblasts/virology Gene Expression Regulation Humans Interferon Regulatory Factor-3 Interferon Type I/metabolism Oligonucleotide Array Sequence Analysis Phosphoproteins/genetics,pharmacology Proteins/genetics,metabolism Proteome Transcription Factors/metabolism Viral Matrix Proteins/genetics,pharmacology
Chemicals
DNA-Binding Proteins IRF3 protein, human Interferon Regulatory Factor-3 Interferon Type I Phosphoproteins Proteins Proteome Transcription Factors Viral Matrix Proteins cytomegalovirus matrix protein 65kDa
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Abate Davide A
Department of Microbiology and Immunology, D 347 Fairchild Science Bldg., Stanford University School of Medicine, Stanford, CA 94305-5124, USA.
Watanabe Shinya
Mocarski Edward S
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.78.20.10995-11006.2004
Published
2004-10-00
Pages
10995-1006
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC521853
Subset
IM
Grants
NIAID NIH HHS · P01 AI050153 · United States
NIAID NIH HHS · R01 AI033852 · United States
NIAID NIH HHS · P01 AI 50153 · United States
NIAID NIH HHS · R01 AI 33852 · United States
External Links
PubMed source DOI: 10.1128/JVI.78.20.10995-11006.2004 PMC Full Text View journal details
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