Conserved Herpesviral Kinase Promotes Viral Persistence by Inhibiting the IRF-3-mediated Type I Interferon Response

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2009 Feb 17

PMID 19218087

Citations 99

Authors

Seungmin Hwang

Kyeong Seon Kim

Emilio Flano

Ting-Ting Wu

Leming M Tong

Ann N Park

Moon Jung Song

David Jesse Sanchez

Ryan M OConnell

Genhong Cheng

Ren Sun

Affiliations

Soon will be listed here.

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.

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