The Gene of Goatpox Virus Encodes an Inhibitor of NF-κB and Apoptosis and May Serve as an Improved Insertion Site To Generate Vectored Live Vaccine.

Goatpox virus (GTPV) is an important member of the genus of the Capripoxviruses have large and complex DNA genomes encoding many unknown proteins that may contribute to virulence. We identified that the open reading frame of GTPV is an early gene that encodes an ∼18-kDa protein that is nonessential for viral replication in cells. This protein functioned as an inhibitor of NF-κB activation and apoptosis and is similar to the N1L protein of vaccinia virus. In the natural host, sheep, deletion of the gene from the GTPV live vaccine strain AV41 resulted in less attenuation than that induced by deletion of the gene, a well-defined nonessential gene in the poxvirus genome. Using the gene as the insertion site, a recombinant AV41 strain expressing hemagglutinin of peste des petits ruminants virus (PPRV) was generated and elicited stronger neutralization antibody responses than those obtained using the traditional gene as the insertion site. These results suggest that the gene of GTPV encodes an immunomodulatory protein to suppress host innate immunity and may serve as an optimized insertion site to generate capripoxvirus-vectored live dual vaccines. Capripoxviruses are etiological agents of important diseases in sheep, goats, and cattle. There are rare reports about viral protein function related to capripoxviruses. In the present study, we found that the 135 protein of GTPV plays an important role in inhibition of innate immunity and apoptosis in host cells. Use of the gene as the insertion site to generate a vectored vaccine resulted in stronger adaptive immune responses than those obtained using the locus as the insertion site. As capripoxviruses are promising virus-vectored vaccines against many important diseases in small ruminants and cattle, the gene may serve as an improved insertion site to generate recombinant capripoxvirus-vectored live dual vaccines.