Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 292, Issue 52, Pages 21291-21303Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M117.805937
Keywords
cytokine induction; cytokine storm; influenza virus; interferon regulatory factor (IRF); microRNA (miRNA); signaling
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Funding
- National Natural Science Foundation of China [31500149, 31570870, 81301428]
- Fundamental Research Funds for the Central Universities [2042017kf0221, 2042015kf0188]
- National Basic Research Program of China (973 Program) [2014CB542603]
- Deutsche Forschungsgemeinschaft [TRR60, RTG1949]
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During influenza A virus (IAV) infection, cytokine storms play a vital and critical role in clinical outcomes. We have previously reported that microRNA (miR)-302c regulates IAV-induced IFN expression by targeting the 3-UTR of nuclear factor B (NF-B)-inducing kinase. In the current study, we found that miR-302a, another member of the miR-302 cluster, controls the IAV-induced cytokine storm. According to results from cell-based and knockout mouse models, IAV induces a cytokine storm via interferon regulatory factor-5 (IRF-5). We also found that IAV infection up-regulates IRF-5 expression and that IRF-5 in turn promotes IAV replication. Furthermore, we observed that IRF-5 is a direct target of miR-302a, which down-regulated IRF-5 expression by binding its 3-UTR. Moreover, IAV increased IRF-5 expression by down-regulating miR-302a expression. Interestingly, miR-302a inhibited IAV replication. In IAV-infected patients, miR-302a expression was down-regulated, whereas IRF-5 expression was up-regulated. Taken together, our work uncovers and defines a signaling pathway implicated in an IAV-induced cytokine storm.
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