HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF-3 recruitment of the CBP/p300 coactivators

Rongtuan Lin, Pierre Genin, Yael Mamane, Marco Sgarbanti, Angela Battistini, William J. Harrington, Glen N. Barber, John Hiscott

Research output: Contribution to journalArticle

173 Scopus citations

Abstract

Human herpes virus 8 (HHV-8) has developed unique mechanisms for altering cellular proliferative and apoptotic control pathways by incorporating viral homologs to several cellular regulatory genes into its genome. One of the important pirated genes encoded by the ORF K9 reading frame is a viral homolog of the interferon regulatory factors (IRF), a family of cellular transcription proteins that regulates expression of genes involved in pathogen response, immune modulation and cell proliferation. vIRF-1 has been shown to down-regulate the interferon- and IRF-mediated transcriptional activation of ISG and murine IFNA4 gene promoters. In this study we demonstrate that vIRF-1 efficiently inhibited virus-induced expression of endogenous interferon B, CC chemokine RANTES and CXC chemokine IP-10 genes. Co-expression analysis revealed that vIRF-1 selectively blocked IRF-3 but not IRF-7-mediated transactivation. vIRF-1 was able to bind to both IRF-3 and IRF-7 in vivo as detected by coimmunoprecipitation analysis, but did not affect IRF-3 dimerization, nuclear translocation and DNA binding activity. Rather, vIRF-1 interacted with the CBP/p300 coactivators and efficiently inhibited the formation of transcriptionally competent IRF-3-CBP/p300 complexes. These results illustrate that vIRF-1 is able to block the early stages of the IFN response to virus infection by interfering with the activation of IRF-3 responsive, immediate early IFN genes.

Original languageEnglish (US)
Pages (from-to)800-811
Number of pages12
JournalOncogene
Volume20
Issue number7
DOIs
StatePublished - Feb 15 2001

Keywords

  • CBP/P300
  • Chemokines
  • Herpes
  • Interferon
  • IRF-3
  • Transcription
  • vIRF-1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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    Lin, R., Genin, P., Mamane, Y., Sgarbanti, M., Battistini, A., Harrington, W. J., Barber, G. N., & Hiscott, J. (2001). HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF-3 recruitment of the CBP/p300 coactivators. Oncogene, 20(7), 800-811. https://doi.org/10.1038/sj.onc.1204163