School of Life Science and Engineering, Foshan University, No. 33, Guangyun Road, Nanhai District, Foshan, 528000, China.
College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, 450046, People's Republic of China.
BMC Vet Res. 2022 May 30;18(1):208. doi: 10.1186/s12917-022-03309-1.
Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious and virulent infectious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV), which has substantial economic losses in the pig industry worldwide, and PRRSV attenuated vaccines and inactivated vaccines do have limitations in immune protection. The discovery of new antiviral targets has become a new research field. The proteomic studies have shown that the PRRSV NSP2 protein interacts with tripartite motif protein 4 (TRIM4), but it was still unknown whether TRIM4 regulates PRRSV infections. In this study, the TRIM4 gene from Marc-145 cells was cloned, and it was proved that TRIM4 overexpression inhibits PRRSV replication, whereas TRIM4 small-interfering-RNA knockdown resulted in increased virus titers. Mechanism investigation indicated that TRIM4 inhibits PRRSV replication through ubiquitination and degradation of the NSP2 protein. Protease inhibitor MG132 (carbobenzoxy-Leu-Leu-leucinal) attenuated the TRIM4-driven degradation of NSP2. Taken together, TRIM4 impairs PRRSV proliferation via ubiquitination and degradation of NSP2.
猪繁殖与呼吸综合征（PRRS）是一种由猪繁殖与呼吸综合征病毒（PRRSV）引起的高度传染性和高致病性传染病，给全球养猪业造成了巨大的经济损失，而 PRRSV 减毒活疫苗和灭活疫苗在免疫保护方面确实存在局限性。寻找新的抗病毒靶点已成为一个新的研究领域。蛋白质组学研究表明，PRRSV 的 NSP2 蛋白与三肽基蛋白 4（TRIM4）相互作用，但 TRIM4 是否调节 PRRSV 感染仍不清楚。在这项研究中，从 Marc-145 细胞中克隆了 TRIM4 基因，证明 TRIM4 过表达抑制了 PRRSV 的复制，而 TRIM4 的小干扰 RNA 敲低导致病毒滴度增加。机制研究表明，TRIM4 通过 NSP2 蛋白的泛素化和降解来抑制 PRRSV 的复制。蛋白酶抑制剂 MG132（carbobenzoxy-Leu-Leu-leucinal）减弱了 TRIM4 驱动的 NSP2 降解。总之，TRIM4 通过 NSP2 的泛素化和降解来损害 PRRSV 的增殖。
