LncRNA <i>JINR1</i> regulates <i>miR-216b-5p/</i> GRP78 and <i>miR-1-3p/</i> DDX5 axis to promote JEV infection and cell death

Infection of the central nervous system (CNS) by Japanese encephalitis virus (JEV) or West Nile virus (WNV) leads to neuroinflammation and neuronal cell death. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) regulate viral infection by regulating the expression of host genes. However, knowledge about the interplay between lncRNAs and miRNAs during JEN/WNV infection is limited. We show that JEV/WNV infection inhibits the expression of anti-viral host miRNAs <i>miR-216b-5p</i> and <i>miR-1-3p</i>. These miRNAs inhibit the JEV and WNV replication by directly binding with their genome. <i>JINR1</i> and its interacting protein, RBM10, inhibit the transcription of <i>miR-216b-5p</i> and <i>miR-1-3p</i>. Interestingly, <i>JINR1</i> also binds and sequesters <i>miR-216b-5p</i> and <i>miR-1-3p</i>, resulting in upregulation of their targets GRP78 and DDX5, respectively, which promote viral infection. Our findings suggest that lncRNA <i>JINR1</i> is a potential target for developing anti-virals against JEV/WNV infection.