MicroRNA-302a suppresses influenza A virus-stimulated interferon regulatory factor-5 expression and cytokine storm induction [Immunology]

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 kappa B (NF-κB)-inducing kinase (NIK). In the current study, we found that miR-302a, another member of miR-302 cluster, controls the IAV-induced cytokine storm. According to results from cell-based and knock-out mouse models, IAV induces a cytokine storm via interferon regulatory factor-5 (IRF-5). We also found that IAV infection upregulates 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 downregulating miR-302a expression. Interestingly, miR-302a inhibited IAV replication. In IAV-infected patients, miR-302a expression was downregulated, whereas IRF-5 expression was upregulated. Taken together, our work uncovers and defines a signaling pathway implicated in an IAV-induced cytokine storm.

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