State Key Laboratory of Veterinary Biotechnology, Mission of Zoonosis and Exotic Diseases, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China.
State Key Laboratory of Veterinary Biotechnology, Mission of Zoonosis and Exotic Diseases, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China
J Virol. 2018 Aug 29;92(18). doi: 10.1128/JVI.00190-18. Print 2018 Sep 15.
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.
山羊痘病毒（GTPV）是 Capripoxviruses 属的重要成员，具有大而复杂的 DNA 基因组，编码许多未知的蛋白质，这些蛋白质可能有助于病毒的毒力。我们鉴定出 GTPV 的 开放阅读框是一个早期基因，它编码一个约 18kDa 的蛋白质，该蛋白质对于细胞中病毒的复制不是必需的。该蛋白质作为 NF-κB 激活和凋亡的抑制剂，与牛痘病毒的 N1L 蛋白相似。在天然宿主绵羊中，从 GTPV 活疫苗株 AV41 中删除 基因导致的减毒作用不如删除痘病毒基因组中明确的非必需基因 基因时明显。使用 基因作为插入位点，生成了表达小反刍动物瘟病毒（PPRV）血凝素的重组 AV41 株，与使用传统的 基因作为插入位点相比，该重组株诱导了更强的中和抗体反应。这些结果表明，GTPV 的 基因编码一种免疫调节蛋白，以抑制宿主固有免疫，并且可以作为优化的插入位点来生成山羊痘病毒载体活双疫苗。山羊痘病毒是绵羊、山羊和牛的重要疾病的病原体。关于与山羊痘病毒相关的病毒蛋白功能的报道很少。在本研究中，我们发现 GTPV 的 135 蛋白在宿主细胞中抑制固有免疫和凋亡中发挥重要作用。使用 基因作为插入位点生成载体疫苗可引起比使用 基因作为插入位点更强的适应性免疫反应。由于山羊痘病毒是针对小反刍动物和牛的许多重要疾病的有前途的病毒载体疫苗，因此 基因可能作为改进的插入位点来生成重组山羊痘病毒载体活双疫苗。
