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J Immunol. 2015 Sep 1;195(5):2251-62. doi: 10.4049/jimmunol.1500370. Epub 2015 Jul 22.

MicroRNA-15b Modulates Japanese Encephalitis Virus-Mediated Inflammation via Targeting RNF125.

Author information

1
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, People's Republic of China; Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, People's Republic of China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, People's Republic of China; and.
2
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, People's Republic of China; Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, People's Republic of China;
3
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, People's Republic of China; Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, People's Republic of China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, People's Republic of China; and Department of Pathology, University of Georgia, Athens, GA 30602.
4
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, People's Republic of China; Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, People's Republic of China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, People's Republic of China; and sbcao@mail.hzau.edu.cn.

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.

PMID:
26202983
DOI:
10.4049/jimmunol.1500370
[Indexed for MEDLINE]
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