Abstract
Influenza A virus (IAV) is responsible for severe morbidity and mortality in animals and humans worldwide. miRNAs are a class of small noncoding single-stranded RNA molecules that can negatively regulate gene expression and play important roles in virus-host interaction. However, the roles of miRNAs in IAV infection are still not fully understood. Here, we profiled the cellular miRNAs of A549 cells infected with A/goose/Jilin/hb/2003 (H5N1) and a comparison A/Beijing/501/2009 (H1N1). miRNA microarray and quantitative PCR analysis showed that several miRNAs were differentially expressed in A549 cells during IAV infection. Subsequently, we demonstrated that IAV replication was essential for the regulation of these miRNAs, and bioinformatic analysis revealed that the targets of these miRNAs affected biological processes relevant to IAV replication. Specifically, miR-21-3p was found to be down-regulated in IAV-infected A549 cells and selected for further detailed analysis. Target prediction and functional study illustrated that miR-21-3p repressed the expression of HDAC8 by targeting its 3′UTR. Furthermore, we confirmed miR-21-3p could promote virus replication, which was similar to the result of knocking down HDAC8, indicating that miR-21-3p promoted IAV replication by suppressing HDAC8 expression. Altogether, our results suggest a potential host defense against IAV through down-regulation of miR-21-3p.
Highlights
Influenza A virus (IAV), a member of the family Orthomyxoviridae, is responsible for severe morbidity and mortality in animals and humans worldwide (Wright et al, 2013)
We identified several miRNAs, including miR-21-3p, which were differentially expressed in IAV-infected A549 cells, and IAV replication was found to be essential for the regulation of these miRNAs
We performed the miRNA expression profile of A549 cells infected with H1N1 and H5N1 as described in the materials and methods section
Summary
Influenza A virus (IAV), a member of the family Orthomyxoviridae, is responsible for severe morbidity and mortality in animals and humans worldwide (Wright et al, 2013). In 2009, a previously undescribed IAV H1N1 emerged in North America and spread to other countries worldwide with a high transmissibility but relative low fatality rate, causing the first pandemic in the twenty-first century (Smith et al, 2009). In 1997, the highly pathogenic H5N1 subtype was first observed to be spread from poultry to humans and cause deaths in Hong Kong (Subbarao et al, 1998). Up to December 2017, more than 860 confirmed cases of human infections with the H5N1 virus, including 454 deaths, have been reported to the World Health Organization with a high fatality rate of approximately 53% (http://www.who.int/influenza/). The case fatality rate of H7N9 virus infection has reached as high as 39% with at least 612 deaths from 1565 confirmed cases miR-21-3p Regulates IAV Replication via HDAC8
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