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MicroRNA-132-3p suppress type I IFN response through targeting IRF1 to facilitate H1N1 influenza A virus infection

tetano

Editor, Senior Moderator
Biosci Rep. 2019 Nov 20. pii: BSR20192769. doi: 10.1042/BSR20192769. [Epub ahead of print] [h=1]MicroRNA-132-3p suppress type I IFN response through targeting IRF1 to facilitate H1N1 influenza A virus infection.[/h]
Zhang F[SUP]1[/SUP], Lin X[SUP]1[/SUP], Yang X[SUP]2[/SUP], Lu G[SUP]2[/SUP], Zhang Q[SUP]3[/SUP], Zhang C[SUP]4[/SUP].
[h=3]Author information[/h] 1 The People's Hospital of Leqing, Leqing, China. 2 Clinical Lab, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China. 3 Blood Transfusion Room, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China. 4 Respiratory Intensive Care Unit, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China.

[h=3]Abstract[/h] Increasing evidence has indicated that microRNAs (miRNAs) have essential roles in innate immune responses to various viral infections; however, the role of miRNAs in H1N1 influenza A virus (IAV) infection is still unclear. The present study aimed to elucidate the role and mechanism of miRNAs in IAV replication in vitro. Using a microarray assay, we analyzed the expression profiles of miRNAs in peripheral blood from IAV patients. It was found that miR-132-3p was significantly upregulated in peripheral blood samples from IAV patients. It was also observed that IAV infection upregulated the expression of miR-132-3p in a dose and time dependent manner. Subsequently, we investigated miR-132-3p function and found that upregulation of miR-132-3p promoted IAV replication, whereas knockdown of miR-132-3p repressed replication. Meanwhile, overexpression of miR-132-3p could inhibit IAV triggered INF-α and INF-β production and IFN-stimulated gene (ISG) expression , including myxovirus protein A (MxA), 2?, 5?-oligoadenylate synthetases (OAS), and double stranded RNA-dependent protein kinase (PKR), while inhibition of miR-132-3p enhanced IAV triggered these effects. Of note, interferon regulatory factor 1 (IRF1), a well-known regulator of the type I IFN response, was identified as a direct target of miR-132-3p during HIN1 IAV infection. Furthermore, knockdown of IRF1 by si-IRF1 reversed the promoting effects of miR-132-3p inhibition on type I IFN response. Taken together, upregulation of miR-132-3p promotes IAV replication by suppressing type I IFN response through its target gene IRF1, suggesting that miR-132-3p could represent a novel potential therapeutic target of IAV treatment.
Copyright 2019 The Author(s).


[h=4]KEYWORDS:[/h] H1N1 IAV; IRF1; Type I IFN; miR-132-3p; replication

PMID: 31746331 DOI: 10.1042/BSR20192769
 
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