A nuclear inhibitor of NF-κB encoded by a poxvirus

D. G. Diel, S. Luo, G. Delhon, Y. Peng, E. F. Flores, D. L. Rock

Research output: Contribution to journalArticle

Abstract

Poxviruses have evolved various strategies to inhibit cytoplasmic events leading to activation of the nuclear factor κB (NF-κB) signaling pathway, with individual viruses often encoding multiple NF-κB inhibitors. Here, the novel orf virus (ORFV)-encoded protein ORFV002 was shown to inhibit nuclear events regulating NF-κB transcriptional activity. ORFV002 expression in cell cultures significantly decreased wild-type-virus-, tumor necrosis factor alpha (TNF-α)-, and lipopolysaccharide (LPS)-induced NF-κB-mediated gene expression. Expression of ORFV002 in cells, while not affecting phosphorylation or nuclear translocation of NF-κB-p65, markedly decreased TNF-α- and wild-type-virus-induced acetylation of NF-κB-p65, a p300-mediated nuclear modification of NF-κB-p65 that regulates its transactivating activity. ORFV002 was shown to colocalize and interact with NF-κB-p65, and expression of ORFV002 in cell cultures resulted in a reduced interaction of NF-κB-p65 with p300, suggesting that ORFV002 interferes with NF-κB-p65/p300 association. Deletion of ORFV002 from the OV-IA82 genome had no significant effect on ORFV pathogenesis in sheep, indicating that ORFV002 is nonessential for virus virulence in the natural host. This represents the first description of a nuclear inhibitor of NF-κB encoded by a poxvirus.

Original languageEnglish (US)
Pages (from-to)264-275
Number of pages12
JournalJournal of virology
Volume85
Issue number1
DOIs
StatePublished - Jan 2011

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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  • Cite this

    Diel, D. G., Luo, S., Delhon, G., Peng, Y., Flores, E. F., & Rock, D. L. (2011). A nuclear inhibitor of NF-κB encoded by a poxvirus. Journal of virology, 85(1), 264-275. https://doi.org/10.1128/JVI.01149-10