| Autor: |
Guo Y; Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, PR China.; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China., Xu X; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.; Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, PR China., Tang T; Department of Laboratory Medicine, Jintang First People's Hospital, West China Hospital Sichuan University JinTang Hospital, Chengdu, Sichuan, PR China., Sun L; Department of Anaesthesia and Pain, The First People's Hospital of Chongqing Liangjiang New Area, Chongqing, PR China., Zhang X; Department of Neurology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China., Shen X; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China., Li D; Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, PR China., Wang L; Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, PR China., Zhao L; Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, PR China., Xie P; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. |
| Abstrakt: |
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. |
