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

Seungmin Hwang, Kyeong Seon Kim, Emilio Flano, Ting Ting Wu, Leming M. Tong, Ann N. Park, Moon Jung Song, David Jesse Sanchez, Ryan M. O'Connell, Genhong Cheng, Ren Sun

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

A conserved herpesviral kinase, designated ORF36 in murine γ-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 β 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.

Original languageEnglish
Pages (from-to)166-178
Number of pages13
JournalCell Host and Microbe
Volume5
Issue number2
DOIs
Publication statusPublished - 2009 Feb 19

Fingerprint

Interferon Regulatory Factor-3
Interferon Type I
Interferons
Phosphotransferases
Rhadinovirus
Herpesviridae
RNA Polymerase II
Virus Diseases
Life Cycle Stages
Antiviral Agents
Immunity
Spleen
Viruses
Lung

Keywords

  • MICROBIO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

Conserved Herpesviral Kinase Promotes Viral Persistence by Inhibiting the IRF-3-Mediated Type I Interferon Response. / Hwang, Seungmin; 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.

In: Cell Host and Microbe, Vol. 5, No. 2, 19.02.2009, p. 166-178.

Research output: Contribution to journalArticle

Hwang, S, Kim, KS, Flano, E, Wu, TT, Tong, LM, Park, AN, Song, MJ, Sanchez, DJ, O'Connell, RM, Cheng, G & Sun, R 2009, 'Conserved Herpesviral Kinase Promotes Viral Persistence by Inhibiting the IRF-3-Mediated Type I Interferon Response', Cell Host and Microbe, vol. 5, no. 2, pp. 166-178. https://doi.org/10.1016/j.chom.2008.12.013
Hwang, Seungmin ; 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. / Conserved Herpesviral Kinase Promotes Viral Persistence by Inhibiting the IRF-3-Mediated Type I Interferon Response. In: Cell Host and Microbe. 2009 ; Vol. 5, No. 2. pp. 166-178.
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