PMID- 35060474 OWN - NLM STAT- MEDLINE DCOM- 20220214 LR - 20220214 IS - 1465-2099 (Electronic) IS - 0022-1317 (Linking) VI - 103 IP - 1 DP - 2022 Jan TI - miR-505 inhibits replication of Borna disease virus 1 via inhibition of HMGB1-mediated autophagy. LID - 10.1099/jgv.0.001713 [doi] AB - Borna disease virus 1 (BoDV-1) is a highly neurotropic RNA virus which was recently demonstrated to cause deadly human encephalitis. Viruses can modulate microRNA expression, in turn modulating cellular immune responses and regulating viral replication. A previous study indicated that BoDV-1 infection down-regulated the expression of miR-505 in rats. However, the underlying mechanism of miR-505 during BoDV-1 infection remains unknown. In this study, we found that miR-505 can inhibit autophagy activation by down-regulating the expression of its target gene HMGB1, and ultimately inhibit the replication of BoDV-1. Specifically, we found that the expression of miR-505 was significantly down-regulated in rat primary neurons stably infected with BoDV-1. Overexpression of miR-505 can inhibit the replication of BoDV-1 in cells. Bioinformatics analysis and dual luciferase reporter gene detection confirmed that during BoDV-1 infection, the high-mobility group protein B1 (HMGB1) that mediates autophagy is the direct target gene of miR-505. The expression of HMGB1 was up-regulated after BoDV-1 infection, and overexpression of miR-505 could inhibit the expression of HMGB1. Autophagy-related detection found that after infection with BoDV-1, the expression of autophagy-related proteins and autophagy-related marker LC3 in neuronal cells was significantly up-regulated. Autophagy flow experiments and transmission electron microscopy also further confirmed that BoDV-1 infection activated HMGB1-mediated autophagy. Further regulating the expression of miR-505 found that overexpression of miR-505 significantly inhibited HMGB1-mediated autophagy. The discovery of this mechanism may provide new ideas and directions for the prevention and treatment of BoDV-1 infection in the future. FAU - Guo, Yujie AU - Guo Y AD - Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, PR China. AD - NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. FAU - Xu, Xiaoyan AU - Xu X AD - NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. AD - Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, PR China. FAU - Tang, Tian AU - Tang T AD - Department of Laboratory Medicine, Jintang First People's Hospital, West China Hospital Sichuan University JinTang Hospital, Chengdu, Sichuan, PR China. FAU - Sun, Lin AU - Sun L AD - Department of Anaesthesia and Pain, The First People's Hospital of Chongqing Liangjiang New Area, Chongqing, PR China. FAU - Zhang, Xiong AU - Zhang X AD - Department of Neurology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. FAU - Shen, Xia AU - Shen X AD - NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. FAU - Li, Dan AU - Li D AD - Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, PR China. FAU - Wang, Lixin AU - Wang L AD - Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, PR China. FAU - Zhao, Libo AU - Zhao L AD - Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, PR China. FAU - Xie, Peng AU - Xie P AD - NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Gen Virol JT - The Journal of general virology JID - 0077340 RN - 0 (HMGB1 Protein) RN - 0 (HMGB1 protein, human) RN - 0 (MIRN505 microRNA, human) RN - 0 (MicroRNAs) SB - IM MH - Animals MH - Autophagy MH - Borna Disease/*genetics/metabolism/*virology MH - Borna disease virus/*physiology MH - HEK293 Cells MH - HMGB1 Protein/*genetics/metabolism MH - Humans MH - MicroRNAs/*genetics/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Virus Replication OTO - NOTNLM OT - BoDV-1 OT - HMGB1 OT - autophagy OT - miR-505 OT - viral replication EDAT- 2022/01/22 06:00 MHDA- 2022/02/15 06:00 CRDT- 2022/01/21 08:44 PHST- 2022/01/21 08:44 [entrez] PHST- 2022/01/22 06:00 [pubmed] PHST- 2022/02/15 06:00 [medline] AID - 10.1099/jgv.0.001713 [doi] PST - ppublish SO - J Gen Virol. 2022 Jan;103(1). doi: 10.1099/jgv.0.001713.