1887

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.

Funding
This study was supported by the:
  • Chongqing Postdoctoral Science Fund Project (Award cstc2019jcyj-bshX0090)
    • Principle Award Recipient: XiaoyanXu
  • Chongqing Postdoctoral Science Fund Project (Award cstc2021jcyj-bsh0015)
    • Principle Award Recipient: YujieGuo
  • Chongqing Postdoctoral Research Special Funding Project (Award 2010010004897023)
    • Principle Award Recipient: YujieGuo
  • Scientific and Technological Research Program of Chongqing Municipal Education Commission (Award KJQN202000432)
    • Principle Award Recipient: LinSun
  • Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission (Award 81820108015)
    • Principle Award Recipient: PengXie
  • Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences and Peking Union Medical College (Award 2019PT320002)
    • Principle Award Recipient: PengXie
  • National Key R&D Program of China (Award 2017YFA0505700)
    • Principle Award Recipient: PengXie
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/content/journal/jgv/10.1099/jgv.0.001713
2022-01-21
2024-04-25
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