miR-505 inhibits replication of Borna disease virus 1 via inhibition of HMGB1-mediated autophagy.

Abstract

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.

• Authors: Yujie Guo, Xiaoyan Xu, Tian Tang, Lin Sun, Xiong Zhang, Xia Shen, Dan Li, Lixin Wang, Libo Zhao, Peng Xie
• Journal: The Journal of general virology (J Gen Virol) Vol. 103 Issue 1 (01 2022) ISSN: 1465-2099 [Electronic] England
• PMID: 35060474 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HMGB1 Protein
• HMGB1 protein, human
• MIRN505 microRNA, human
• MicroRNAs

Topics

• Animals
• Autophagy
• Borna Disease (genetics, metabolism, virology)
• Borna disease virus (physiology)
• HEK293 Cells
• HMGB1 Protein (genetics, metabolism)
• Humans
• MicroRNAs (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Virus Replication