title: Orf virus ORFV121 encodes a novel inhibitor of NF-kappaB that contributes to virus virulence.
abstract: Orf virus (ORFV), the type member of the genus Parapoxvirus of the Poxviridae, has evolved novel strategies (proteins and/or mechanisms of action) to modulate host cell responses regulated by the nuclear factor-κB (NF-κB) signaling pathway. Here, we present data indicating that ORFV ORFV121, a gene unique to parapoxviruses, encodes a novel viral NF-κB inhibitor that binds to and inhibits the phosphorylation and nuclear translocation of NF-κB-p65. The infection of cells with an ORFV121 deletion mutant virus (OV-IA82Δ121) resulted in increased NF-κB-mediated gene transcription, and the expression of ORFV121 in cell cultures significantly suppressed NF-κB-regulated reporter gene expression. ORFV ORFV121 physically interacts with NF-κB-p65 in the cell cytoplasm, thus providing a mechanism for the inhibition of NF-κB-p65 phosphorylation and nuclear translocation. Notably, the deletion of ORFV121 from the viral genome markedly decreased ORFV virulence and disease pathogenesis in sheep, indicating that ORFV121 is a virulence determinant for ORFV in the natural host.
authors.affiliation: University of Illinois, Urbana 61802, IL, USA.
authors.forename: D G
authors.initials: DG
authors.lastname: Diel
authors.forename: S
authors.initials: S
authors.lastname: Luo
authors.forename: G
authors.initials: G
authors.lastname: Delhon
authors.forename: Y
authors.initials: Y
authors.lastname: Peng
authors.forename: E F
authors.initials: EF
authors.lastname: Flores
authors.forename: D L
authors.initials: DL
authors.lastname: Rock
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D004474:Ecthyma, Contagious / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006801:Humans; D009923:Orf virus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D012756:Sheep; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D051996:Transcription Factor RelA; D014764:Viral Proteins