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PMID: 19218087 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Conserved herpesviral kinase promotes viral persistence by inhibiting the IRF-3-mediated type I interferon response.

Cell host & microbe ·Vol. 5 ·No. 2 ·2009-02-19 ·Pages 166-78

Hwang S, Kim KS, Flano E, Wu TT, Tong LM, Park AN, Song MJ, Sanchez DJ, O'Connell RM, Cheng G, Sun R

Abstract

A conserved herpesviral kinase, designated ORF36 in murine gamma-herpesvirus 68 (MHV-68), plays multiple vital roles in the viral life cycle. Here, we show by screening mutant viruses that ORF36 counteracts the antiviral type I interferon (IFN) response. ORF36 specifically binds to the activated form of interferon regulatory factor 3 (IRF-3) in the nucleus, inhibiting IRF-3 interaction with the cotranscriptional activator CBP and thereby suppressing the recruitment of RNA polymerase II to the interferon beta promoter. The anti-IFN function of ORF36 is conserved among herpesvirus subfamilies, although the conserved kinase activity is not absolutely required for this function. MHV-68 lacking ORF36 induces a greater interferon response and is attenuated in vitro and in vivo, where acute viral infection in the lung and latency in the spleen are compromised. Our data suggest that herpesviruses have evolved within their conserved kinase an anti-IFN activity critical for evasion of host immunity and for persistence.

MeSH Terms
Animals Herpesviridae Infections/immunology Interferon Regulatory Factor-3/antagonists & inhibitors Interferon Type I/biosynthesis Lung/immunology,virology Membrane Proteins/metabolism Mice Phosphoproteins/metabolism Protein Binding Protein Kinases/genetics,metabolism Rhadinovirus/genetics,pathogenicity Spleen/immunology,virology Viral Proteins/genetics,metabolism Virulence Virulence Factors/genetics,metabolism
Chemicals
Interferon Regulatory Factor-3 Interferon Type I Membrane Proteins Pag1 protein, mouse Phosphoproteins Viral Proteins Virulence Factors Protein Kinases
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Hwang Seungmin
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Kim Kyeong Seon
Flano Emilio
Wu Ting-Ting
Tong Leming M
Park Ann N
Song Moon Jung
Sanchez David Jesse
O'Connell Ryan M
Cheng Genhong
Sun Ren
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Article Info
Journal
Cell host & microbe
Abbr.
Cell Host Microbe
ISSN
1934-6069
DOI
10.1016/j.chom.2008.12.013
Published
2009-02-19
Pages
166-78
Language
English
Region
United States
NLM ID
101302316
PMCID
PMC2749518
Subset
IM
Grants
NIDCR NIH HHS · P01 DE019085 · United States
NIDCR NIH HHS · R01 DE015752 · United States
NIDCR NIH HHS · P01-DE019085 · United States
NIAID NIH HHS · AI28697 · United States
NIAID NIH HHS · T32AI060567 · United States
NIDCR NIH HHS · R01-DE15752 · United States
NIDCR NIH HHS · P01 DE019085-01 · United States
NIDCR NIH HHS · K22 DE015612 · United States
NIDCR NIH HHS · R01 DE015752-05 · United States
NIDCR NIH HHS · K22 DE015612-05 · United States
NIAID NIH HHS · R01-AI59603 · United States
NCI NIH HHS · R21 CA120761-02 · United States
NIAID NIH HHS · T32 AI060567 · United States
NCI NIH HHS · R21-CA120761 · United States
NCI NIH HHS · R21 CA120761 · United States
NCI NIH HHS · P50 CA086306 · United States
NCI NIH HHS · P50-CA86306 · United States
NIAID NIH HHS · R01 AI059603 · United States
NIDCR NIH HHS · DE015612 · United States
NIAID NIH HHS · P30 AI028697 · United States
External Links
PubMed source DOI: 10.1016/j.chom.2008.12.013 PMC Full Text View journal details
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