A nuclear inhibitor of NF-kappaB encoded by a poxvirus.
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.
Diel
D G
DG
Department of Pathobiology, College of Veterinary Medicine, University of Illinois, MC-002, 2001 S. Lincoln Avenue, Urbana, IL 61802, USA.
Luo
S
S
Delhon
G
G
Peng
Y
Y
Flores
E F
EF
Rock
D L
DL
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D004474:Ecthyma, Contagious / Q000473:pathology / Q000821:virology; D005786:Gene Expression Regulation; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics; D009923:Orf virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D012756:Sheep; D015398:Signal Transduction; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D014764:Viral Proteins