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Zhang M, Sun Y, Chen W, Bu Z. The 135 gene of goatpox virus encodes an inhibitor of nuclear factor-κB and apoptosis and may serve as an improved insertion site to generate vectored live vaccine. J Virol. 2018 Jun 27

发布日期:2018-07-05 15:17  浏览次数:

The 135 gene of goatpox virus encodes an inhibitor of nuclear factor-κB and apoptosis and may serve as an improved insertion site to generate vectored live vaccine.
Minmin Zhang , Yirui Sun , Weiye Chen , Zhigao Bu
J Virol. 2018 Jun 27. pii: JVI.00190-18. doi: 10.1128/JVI.00190-18

Abstract
Goatpox virus (GTPV) is an important member of the Capripoxvirus genus of the Poxviridae Capripoxviruses have large and complex DNA genomes encoding many unknown proteins that may contribute to virulence. We identified that the 135 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 nuclear factor-κB activation and apoptosis, and is similar to N1L protein of vaccinia virus. In the natural host, sheep, deletion of the 135 gene of GTPV live vaccine strain AV41 resulted in less attenuation than that induced by deletion of the tk gene; a well-defined nonessential gene in the poxvirus genome. Using the 135 gene as the insertion site, a recombinant AV41 expressing hemagglutinin of peste des petits ruminants virus (PPRV) was generated and elicited stronger neutralization antibody responses than that using the traditional tk gene. These results suggest that 135 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.ImportanceCapripoxviruses are etiological agents of important diseases in sheep, goats and cattle. There are rare reports about viral protein function related to capripoxviruses. Here, 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 135 gene as the insertion site to generate vectored vaccine resulted in stronger adaptive immune responses than using the tk locus. As capripoxviruses are promising viral-vectored vaccines against many important diseases in small ruminates and cattle, the 135 gene may serve as an improved insertion site to generate recombinant capripoxviruses vectored live dual vaccines.

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