Abstract
MicroRNAs (miRNAs) are small noncoding RNA molecules that play important roles in various biological processes. Much evidence shows that miRNAs are closely associated with numerous virus infections; however, involvement of cellular miRNAs in influenza A virus (IAV) infection is unclear. Here, we found that expression of miR-203 was up-regulated markedly via two different mechanisms during IAV infection. First, we examined the effects of type I interferon induced by IAV on direct activation of miR-203 expression. Next, we showed that DNA demethylation within the miR-203 promoter region in A549 cells induced its up-regulation, and that expression of DNA methyltransferase 1 was down-regulated following H5N1 virus infection. Ectopic expression of miR-203 in turn inhibited H5N1 virus replication by targeting down-regulator of transcription 1 (DR1), which was identified as a novel target of miR-203. Silencing DR1 in miR-203 knockout cells using a specific siRNA inhibited replication of the H5N1 virus, an effect similar to that of miR-203. In summary, the data show that host cell expression of miR-203 is up-regulated upon IAV infection, which increases antiviral responses by suppressing a novel target gene, DR1. Thus, we have identified a novel mechanism underlying the relationship between miR-203 and IAV infection.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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A549 Cells
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Animals
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Antagomirs / genetics
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Antagomirs / metabolism
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Base Sequence
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Binding Sites
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Chlorocebus aethiops
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DNA (Cytosine-5-)-Methyltransferase 1 / antagonists & inhibitors
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DNA (Cytosine-5-)-Methyltransferase 1 / genetics
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DNA (Cytosine-5-)-Methyltransferase 1 / metabolism
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DNA Demethylation
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Gene Expression Regulation
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Host-Pathogen Interactions / genetics*
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Host-Pathogen Interactions / immunology
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Humans
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Influenza A Virus, H1N1 Subtype / genetics*
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Influenza A Virus, H1N1 Subtype / metabolism
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Influenza A Virus, H3N2 Subtype / genetics
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Influenza A Virus, H3N2 Subtype / metabolism
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Influenza A Virus, H5N1 Subtype / genetics
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Influenza A Virus, H5N1 Subtype / metabolism
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Influenza A Virus, H7N9 Subtype / genetics
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Influenza A Virus, H7N9 Subtype / metabolism
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Interferon-alpha / genetics*
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Interferon-alpha / metabolism
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Interferon-beta / genetics*
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Interferon-beta / metabolism
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Phosphoproteins / antagonists & inhibitors
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Phosphoproteins / genetics*
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Phosphoproteins / metabolism
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Promoter Regions, Genetic
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Signal Transduction
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Vero Cells
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Virus Replication
Substances
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Antagomirs
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Interferon-alpha
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MIRN203 microRNA, human
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MicroRNAs
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Phosphoproteins
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RNA, Small Interfering
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Transcription Factors
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down-regulator of transcription 1
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Interferon-beta
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DNA (Cytosine-5-)-Methyltransferase 1
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DNMT1 protein, human