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

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Biosci Rep. 2019 Nov 20. pii: BSR20192769. doi: 10.1042/BSR20192769. [Epub ahead of print] MicroRNA-132-3p suppress type I IFN response through targeting IRF1 to facilitate H1N1 influenza A virus infection.

Zhang F¹, Lin X¹, Yang X², Lu G², Zhang Q³, Zhang C⁴.
Author information

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.

Abstract

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).


KEYWORDS:

H1N1 IAV; IRF1; Type I IFN; miR-132-3p; replication

PMID: 31746331 DOI: 10.1042/BSR20192769