PMID- 32753633 OWN - NLM STAT- MEDLINE DCOM- 20201208 LR - 20210804 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 10 IP - 1 DP - 2020 Aug 4 TI - Porcine reproductive and respiratory syndrome virus infection induces endoplasmic reticulum stress, facilitates virus replication, and contributes to autophagy and apoptosis. PG - 13131 LID - 10.1038/s41598-020-69959-z [doi] LID - 13131 AB - During viral infection, the host cell synthesizes high amounts of viral proteins, which often causes stress to the endoplasmic reticulum (ER). To manage abnormal ER stress, mammalian cells trigger a response called the unfolded protein response (UPR). Previous studies have indicated that porcine reproductive and respiratory syndrome virus (PRRSV), an Arterivirus that has been devastating the swine industry worldwide, can induce ER stress and activate UPR, however, the activation pathways and the biological significance requires further investigation. In this study, we demonstrated that, among the three types of UPR pathways, PRRSV infection induced PERK and IRE1 pathways, but not the ATF6 pathway. Furthermore, the induction of UPR promoted PRRSV replication. We also found that PRRSV-induced UPR, particularly the PERK pathway, was involved in the induction of autophagy, a cellular degradation process that can alleviate cell stress. Besides, we also provided insights into the ER stress-mediated apoptosis in response to PRRSV infection. PRRSV infection induced the expression of the transcription factor CHOP, which activated caspase 3 and PARP led to ER stress-mediated apoptosis. Using 3-Methyladenine (3-MA) to inhibit autophagy, the increased ER stress and cell apoptosis were observed in the PRRSV infected cell. Taken together, our results revealed the associations of ER stress, autophagy, and apoptosis during PRRSV infection, helping us to further understand how PRRSV interacts with host cells. FAU - Chen, Quangang AU - Chen Q AD - School of Life Science, Xuzhou Medical University, Xuzhou, 221004, China. FAU - Men, Yanjuan AU - Men Y AD - School of Life Science, Xuzhou Medical University, Xuzhou, 221004, China. FAU - Wang, Dang AU - Wang D AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China. AD - Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, China. FAU - Xu, Deqin AU - Xu D AD - Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221004, China. FAU - Liu, Suyan AU - Liu S AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China. AD - Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, China. FAU - Xiao, Shaobo AU - Xiao S AUID- ORCID: 0000-0003-0023-9188 AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China. AD - Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, China. FAU - Fang, Liurong AU - Fang L AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China. fanglr@mail.hzau.edu.cn. AD - Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, China. fanglr@mail.hzau.edu.cn. LA - eng GR - BK20170251/Natural Science Foundation of Jiangsu province/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200804 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 SB - IM MH - Animals MH - *Apoptosis MH - *Autophagy MH - Cell Line MH - *Endoplasmic Reticulum Stress MH - Porcine Reproductive and Respiratory Syndrome/*metabolism MH - Porcine respiratory and reproductive syndrome virus/*physiology MH - Swine MH - *Virus Replication PMC - PMC7403369 COIS- The authors declare no competing interests. EDAT- 2020/08/06 06:00 MHDA- 2020/12/15 06:00 PMCR- 2020/08/04 CRDT- 2020/08/06 06:00 PHST- 2020/02/10 00:00 [received] PHST- 2020/07/16 00:00 [accepted] PHST- 2020/08/06 06:00 [entrez] PHST- 2020/08/06 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2020/08/04 00:00 [pmc-release] AID - 10.1038/s41598-020-69959-z [pii] AID - 69959 [pii] AID - 10.1038/s41598-020-69959-z [doi] PST - epublish SO - Sci Rep. 2020 Aug 4;10(1):13131. doi: 10.1038/s41598-020-69959-z.