University of Illinois, Urbana 61802, IL, USA.
J Virol. 2011 Mar;85(5):2037-49. doi: 10.1128/JVI.02236-10. Epub 2010 Dec 22.
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.
口疮病毒（ORFV）是痘病毒科副痘病毒属的模式成员，它进化出了新的策略（蛋白质和/或作用机制）来调节宿主细胞对核因子-κB（NF-κB）信号通路的反应。在这里，我们提供的数据表明，口疮病毒的 ORFV121 基因是副痘病毒所特有的，它编码了一种新型的病毒 NF-κB 抑制剂，该抑制剂能结合并抑制 NF-κB-p65 的磷酸化和核转位。用 ORFV121 缺失突变病毒（OV-IA82Δ121）感染细胞会导致 NF-κB 介导的基因转录增加，而在细胞培养物中表达 ORFV121 则显著抑制了 NF-κB 调节的报告基因表达。ORFV 的 ORFV121 与 NF-κB-p65 在细胞质中发生物理相互作用，从而为抑制 NF-κB-p65 的磷酸化和核转位提供了一种机制。值得注意的是，从病毒基因组中删除 ORFV121 会显著降低绵羊中 ORFV 的毒力和疾病发病机制，表明 ORFV121 是 ORFV 在天然宿主中的一个毒力决定因素。
