MicroRNA-15b Modulates Japanese Encephalitis Virus-Mediated Inflammation via Targeting RNF125
- PMID: 26202983
- DOI: 10.4049/jimmunol.1500370
MicroRNA-15b Modulates Japanese Encephalitis Virus-Mediated Inflammation via Targeting RNF125
Abstract
Japanese encephalitis virus (JEV) can target CNS and cause neuroinflammation that is characterized by profound neuronal damage and concomitant microgliosis/astrogliosis. Although microRNAs (miRNAs) have emerged as a major regulatory network with profound effects on inflammatory response, it is less clear how they regulate JEV-induced inflammation. In this study, we found that miR-15b is involved in modulating the JEV-induced inflammatory response. The data demonstrate that miR-15b is upregulated during JEV infection of glial cells and mouse brains. In vitro overexpression of miR-15b enhances the JEV-induced inflammatory response, whereas inhibition of miR-15b decreases it. Mechanistically, ring finger protein 125 (RNF125), a negative regulator of RIG-I signaling, is identified as a direct target of miR-15b in the context of JEV infection. Furthermore, inhibition of RNF125 by miR-15b results in an elevation in RIG-I levels, which, in turn, leads to a higher production of proinflammatory cytokines and type I IFN. In vivo knockdown of virus-induced miR-15b by antagomir-15b restores the expression of RNF125, reduces the production of inflammatory cytokines, attenuates glial activation and neuronal damage, decreases viral burden in the brain, and improves survival in the mouse model. Taken together, our results indicate that miR-15b modulates the inflammatory response during JEV infection by negative regulation of RNF125 expression. Therefore, miR-15b targeting may constitute an interesting and promising approach to control viral-induced neuroinflammation.
Copyright © 2015 by The American Association of Immunologists, Inc.
Similar articles
-
MicroRNA-19b-3p Modulates Japanese Encephalitis Virus-Mediated Inflammation via Targeting RNF11.J Virol. 2016 Apr 14;90(9):4780-4795. doi: 10.1128/JVI.02586-15. Print 2016 May. J Virol. 2016. PMID: 26937036 Free PMC article.
-
miR-146a negatively regulates the induction of proinflammatory cytokines in response to Japanese encephalitis virus infection in microglial cells.Arch Virol. 2017 Jun;162(6):1495-1505. doi: 10.1007/s00705-017-3226-3. Epub 2017 Feb 11. Arch Virol. 2017. PMID: 28190197
-
MicroRNA 155 regulates Japanese encephalitis virus-induced inflammatory response by targeting Src homology 2-containing inositol phosphatase 1.J Virol. 2014 May;88(9):4798-810. doi: 10.1128/JVI.02979-13. Epub 2014 Feb 12. J Virol. 2014. PMID: 24522920 Free PMC article.
-
A Review of miRNA Regulation in Japanese Encephalitis (JEV) Virus Infection.Curr Pharm Biotechnol. 2024;25(5):521-533. doi: 10.2174/0113892010241606231003102047. Curr Pharm Biotechnol. 2024. PMID: 37888811 Review.
-
Recent advances in understanding Japanese encephalitis.F1000Res. 2019 Nov 13;8:F1000 Faculty Rev-1915. doi: 10.12688/f1000research.19693.1. eCollection 2019. F1000Res. 2019. PMID: 31781366 Free PMC article. Review.
Cited by
-
ISGylation is induced in neurons by demyelination driving ISG15-dependent microglial activation.J Neuroinflammation. 2022 Oct 20;19(1):258. doi: 10.1186/s12974-022-02618-4. J Neuroinflammation. 2022. PMID: 36261842 Free PMC article.
-
Involvement of host microRNAs in flavivirus-induced neuropathology: An update.J Biosci. 2022;47(3):54. doi: 10.1007/s12038-022-00288-1. J Biosci. 2022. PMID: 36222134 Free PMC article. Review.
-
MicroRNA-22 negatively regulates poly(I:C)-triggered type I interferon and inflammatory cytokine production via targeting mitochondrial antiviral signaling protein (MAVS).Oncotarget. 2016 Nov 22;7(47):76667-76683. doi: 10.18632/oncotarget.12395. Oncotarget. 2016. PMID: 27705941 Free PMC article.
-
Interplay between Inflammation and Cellular Stress Triggered by Flaviviridae Viruses.Front Microbiol. 2016 Aug 25;7:1233. doi: 10.3389/fmicb.2016.01233. eCollection 2016. Front Microbiol. 2016. PMID: 27610098 Free PMC article. Review.
-
Gga-miR-19b-3p Inhibits Newcastle Disease Virus Replication by Suppressing Inflammatory Response via Targeting RNF11 and ZMYND11.Front Microbiol. 2019 Aug 27;10:2006. doi: 10.3389/fmicb.2019.02006. eCollection 2019. Front Microbiol. 2019. PMID: 31507581 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases