An RBM10 and NF-κB interacting host lncRNA promotes JEV replication and neuronal cell death

J Virol. 2023 Dec 21;97(12):e0118323. doi: 10.1128/jvi.01183-23. Epub 2023 Nov 22.

Abstract

Central nervous system infection by flaviviruses such as Japanese encephalitis virus, Dengue virus, and West Nile virus results in neuroinflammation and neuronal damage. However, little is known about the role of long non-coding RNAs (lncRNAs) in flavivirus-induced neuroinflammation and neuronal cell death. Here, we characterized the role of a flavivirus-induced lncRNA named JINR1 during the infection of neuronal cells. Depletion of JINR1 during virus infection reduces viral replication and cell death. An increase in GRP78 expression by JINR1 is responsible for promoting virus replication. Flavivirus infection induces the expression of a cellular protein RBM10, which interacts with JINR1. RBM10 and JINR1 promote the proinflammatory transcription factor NF-κB activity, which is detrimental to cell survival.

Keywords: DENV; ER stress; GRP78; JEV; LINC01518; NF-κB; RBM10; WNV; flavivirus; lncRNAs.

MeSH terms

  • Cell Death*
  • Encephalitis Virus, Japanese* / growth & development
  • Encephalitis Virus, Japanese* / pathogenicity
  • Humans
  • NF-kappa B* / metabolism
  • Neuroinflammatory Diseases / pathology
  • Neuroinflammatory Diseases / virology
  • Neurons* / pathology
  • Neurons* / virology
  • RNA, Long Noncoding* / genetics
  • RNA-Binding Proteins* / metabolism
  • Virus Replication

Substances

  • NF-kappa B
  • RBM10 protein, human
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • HSPA5 protein, human