PMID- 35637527 OWN - NLM STAT- MEDLINE DCOM- 20220602 LR - 20220716 IS - 1746-6148 (Electronic) IS - 1746-6148 (Linking) VI - 18 IP - 1 DP - 2022 May 30 TI - TRIM4-mediated ubiquitination of NSP2 restricts porcine reproductive and respiratory syndrome virus proliferation. PG - 208 LID - 10.1186/s12917-022-03309-1 [doi] LID - 208 AB - 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. CI - (c) 2022. The Author(s). FAU - Zhao, Mengmeng AU - Zhao M AD - School of Life Science and Engineering, Foshan University, No. 33, Guangyun Road, Nanhai District, Foshan, 528000, China. FAU - Sha, Huiyang AU - Sha H AD - School of Life Science and Engineering, Foshan University, No. 33, Guangyun Road, Nanhai District, Foshan, 528000, China. FAU - Zhang, Hang AU - Zhang H AD - School of Life Science and Engineering, Foshan University, No. 33, Guangyun Road, Nanhai District, Foshan, 528000, China. FAU - Wang, Ruining AU - Wang R AD - College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, 450046, People's Republic of China. 80882@hnuahe.edu.cn. LA - eng PT - Journal Article DEP - 20220530 PL - England TA - BMC Vet Res JT - BMC veterinary research JID - 101249759 RN - 0 (Antiviral Agents) SB - IM MH - Animals MH - Antiviral Agents MH - Cell Proliferation MH - *Porcine respiratory and reproductive syndrome virus MH - Proteomics MH - Swine MH - Ubiquitination MH - Virus Replication PMC - PMC9149334 OTO - NOTNLM OT - Degradation OT - NSP2 OT - PRRSV OT - TRIM4 OT - Ubiquitination COIS- The authors declare that they have no competing interests. EDAT- 2022/06/01 06:00 MHDA- 2022/06/03 06:00 PMCR- 2022/05/30 CRDT- 2022/05/31 14:09 PHST- 2021/08/18 00:00 [received] PHST- 2022/05/16 00:00 [accepted] PHST- 2022/05/31 14:09 [entrez] PHST- 2022/06/01 06:00 [pubmed] PHST- 2022/06/03 06:00 [medline] PHST- 2022/05/30 00:00 [pmc-release] AID - 10.1186/s12917-022-03309-1 [pii] AID - 3309 [pii] AID - 10.1186/s12917-022-03309-1 [doi] PST - epublish SO - BMC Vet Res. 2022 May 30;18(1):208. doi: 10.1186/s12917-022-03309-1.