1. Inhibition of miR-93 promotes interferon effector signaling to suppress influenza A infection by upregulating JAK1.
- Author
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Guo M, Li F, Ji J, Liu Y, Liu F, Zhao Y, Li J, Han S, Wang Q, and Ding G
- Subjects
- Animals, Antagomirs administration & dosage, Cell Line, Gene Expression Regulation, Humans, Interferons genetics, Interferons metabolism, Janus Kinase 1 genetics, Janus Kinase 1 metabolism, MAP Kinase Kinase 4 metabolism, Male, Mice, Mice, Inbred C57BL, Receptors, Cell Surface metabolism, Signal Transduction, Influenza A virus physiology, Influenza, Human immunology, MicroRNAs genetics, Orthomyxoviridae Infections immunology
- Abstract
Type I interferons play a critical role in host defense against influenza virus infection. Interferon cascade induces the expression of interferon-stimulated genes then subsequently promotes antiviral immune responses. The microRNAs are important regulators of innate immunity, but microRNAs-mediated regulation of interferon cascade during influenza infection remains to be fully identified. Here we found influenza A virus (IAV) infection significantly inhibited miR-93 expression in alveolar epithelial type II cells through RIG-I/JNK pathway. IAV-induced downregulation of miR-93 was found to upregulate JAK1, the target of miR-93, and then feedback promote antiviral innate response by facilitating IFN effector signaling. Importantly, in vivo administration of miR-93 antagomiR markedly suppressed IAV infection, protecting mice form IAVs -associated death. Hence, the inducible downregulation of miR-93 feedback suppress IAV infection by strengthening IFN-JAK-STAT pathway via JAK1 upregulation, and in vivo inhibition of miR-93 bears considerable therapeutic potential for suppressing IAV infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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