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 κB (NF-κB)-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 downregulated 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.
CITATION STYLE
Chen, X., Zhou, L., Peng, N., Yu, H., Li, M., Cao, Z., … Liu, S. (2017). MicroRNA-302a suppresses influenza A virus-stimulated interferon regulatory factor-5 expression and cytokine storm induction. Journal of Biological Chemistry, 292(52), 21291–21303. https://doi.org/10.1074/jbc.M117.805937
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