College of Veterinary Medicine, South China Agricultural University, No.483, Wushan Road, Tianhe District, Guangzhou, 510640, PR China.
College of Veterinary Medicine, South China Agricultural University, No.483, Wushan Road, Tianhe District, Guangzhou, 510640, PR China.
Virology. 2019 Nov;537:74-83. doi: 10.1016/j.virol.2019.05.017. Epub 2019 Aug 23.
Classical swine fever (CSF) is a major infectious disease of pigs caused by classical swine fever virus (CSFV). NS3 is one of the non-structural proteins of CSFV and plays an important role in the infection process. However, the NS3-interacting cellular proteins involved in viral replication are poorly documented. In this study, proteasome subunit beta 10 (PSMB10) was identified as a novel NS3-interacting partner using yeast two-hybrid screening of a porcine peripheral blood mononuclear cell (PBMC) cDNA library. The PSMB10-NS3 interaction was confirmed by co-immunoprecipitation, glutathione S-transferase pulldown, and laser confocal microscopy. Overexpression of PSMB10 inhibited CSFV replication. Conversely, CSFV infection inhibited PSMB10 expression. Furthermore, we demonstrated that NS3 is degraded by PSMB10 through the ubiquitin-proteasome system and that CSFV inhibits the expression of MHC class I antigen presentation-related transporter proteins, whereas PSMB10 can restore the function of MHC class I antigen presentation and inhibit CSFV proliferation.
经典猪瘟(CSF)是由经典猪瘟病毒(CSFV)引起的一种主要的猪传染病。NS3 是 CSFV 的非结构蛋白之一,在感染过程中发挥重要作用。然而,涉及病毒复制的与 NS3 相互作用的细胞蛋白的研究还很少。在这项研究中,使用猪外周血单核细胞(PBMC)cDNA 文库的酵母双杂交筛选,鉴定了蛋白酶体亚基β10(PSMB10)作为一种新的 NS3 相互作用伙伴。通过共免疫沉淀、谷胱甘肽 S-转移酶下拉和激光共聚焦显微镜证实了 PSMB10-NS3 相互作用。PSMB10 的过表达抑制了 CSFV 的复制。相反,CSFV 感染抑制了 PSMB10 的表达。此外,我们证明 NS3 通过泛素-蛋白酶体系统被 PSMB10 降解,CSFV 抑制 MHC Ⅰ类抗原呈递相关转运蛋白的表达,而 PSMB10 可以恢复 MHC Ⅰ类抗原呈递的功能并抑制 CSFV 的增殖。