title: The host microRNA miR-301a blocks the IRF1-mediated neuronal innate immune response to Japanese encephalitis virus infection.
abstract: Effective recognition of viral components and the subsequent stimulation of the production of type I interferons (IFNs) is crucial for the induction of host antiviral immunity. The failure of the host to efficiently produce type I IFNs in response to infection by the Japanese encephalitis virus (JEV) is linked with an increased probability for the disease to become lethal. JEV is a neurotropic virus of theFlaviviridaefamily that causes encephalitis in humans. JEV infection is regulated by several host factors, including microRNAs, which are conserved noncoding RNAs that participate in various physiological and pathological processes. We showed that the JEV-induced expression ofmiR-301aled to inhibition of the production of type I IFN by reducing the abundances of the transcription factor IFN regulatory factor 1 (IRF1) and the signaling protein suppressor of cytokine signaling 5 (SOCS5). Mechanistically, induction ofmiR-301aexpression during JEV infection required the transcription factor nuclear factor κB. In mouse neurons, neutralization of miR-301a restored the host innate immune response by enabling IFN-β production, thereby restricting viral propagation. Inhibition of miR-301a in mouse brain rescued the production of IRF1 and SOCS5, increased the generation of IFN-β, and reduced the extent of JEV replication, thus improving mouse survival. Thus, our study suggests that the JEV-induced expression ofmiR-301aassists viral pathogenesis by suppressing IFN production, which might be targeted by antiviral therapies.
authors.affiliation: National Brain Research Centre, Manesar, Haryana 122051, India.
authors.forename: Bibhabasu
authors.identifier: 0000-0002-0074-1920
authors.initials: B
authors.lastname: Hazra
authors.affiliation: National Brain Research Centre, Manesar, Haryana 122051, India.
authors.forename: Kanhaiya Lal
authors.identifier: 0000-0002-8373-1065
authors.initials: KL
authors.lastname: Kumawat
authors.affiliation: National Brain Research Centre, Manesar, Haryana 122051, India. anirban@nbrc.ac.in.
authors.forename: Anirban
authors.identifier: 0000-0002-5200-2054
authors.initials: A
authors.lastname: Basu
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004664:Encephalitis Virus, Japanese / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D050856:Interferon Regulatory Factor-1 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D009474:Neurons / Q000378:metabolism* / Q000821:virology; D015398:Signal Transduction / Q000235:genetics; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D050856:Interferon Regulatory Factor-1; C550735:MIRN301A microRNA, human; C573832:MIRN301 microRNA, mouse; D035683:MicroRNAs; C408990:SOCS5 protein, human; C485811:Socs5 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins