Orf Virus ORFV121 Encodes a Novel Inhibitor of NF-κB 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-B (NF-B) signaling pathway. Here, we present data indicating that ORFV ORFV121, a gene unique to parapoxviruses, encodes a novel viral NF-B inhibitor that binds to and inhibits the phosphorylation and nuclear translocation of NF-B-p65. The infection of cells with an ORFV121 deletion mutant virus (OV-IA82⌬121) resulted in increased NF-B-mediated gene transcription, and the expression of ORFV121 in cell cultures significantly suppressed NF-B-regulated reporter gene expression. ORFV ORFV121 physically interacts with NF-B-p65 in the cell cytoplasm, thus providing a mechanism for the inhibition of NF-B-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.

Effect of ORF119 gene deletion on the replication and virulence of orf virus

“…Westphal et al (2009) utilized vaccinia and ORFV virus recombinant technology to study the biological function of ORF125 and demonstrated that ORF125 is capable of inhibiting the activity of Bcl-2 and apoptosis in the host cells to facilitate viral replication. Diel et al, found that ORF121-encoded protein can inhibit NF-κB signaling pathway, thereby inhibiting the secretion of a number of important cytokines and immune response of host cells (Diel et al, 2011). However, the function of many genes encoded by the terminal ITRs (ORFs 001-008 and 112-134) has not been elucidated.…”

Isolation and Characterization of Monoclonal Antibodies Against a Virion Core Protein of Orf Virus Strain NA1/11 As Potential Diagnostic Tool for Orf Viruses

“…(4)(5)(6) ORFV is a Parapoxvirus of the subfamily Chordopoxvirinae and the family Poxviridae. (7) Bovine papular stomatitis virus and pseudocowpox virus are additional members of this genus. (7) The complete genome of the orf virus is 138 kb, contains 64% GC, and includes 132 putative genes.…”

Parapoxvirusorf virus infection induces an increase in interleukin-8, tumour necrosis factor-α, and decorin in goat skin fibroblast cells

“…After ORFV infection, dendritic cells, neutrophils, T cells, and B cells accumulate at the infection site (13). ORFV encodes several genes that inhibit the immune response of the host by inhibiting apoptosis, interferon production, inflammatory reaction, and NF-kB signalling (5,7,12,26). Cytokines, which play an important role in the innate immune response after viral infection, might also be affected by the virus.…”