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Sus scrofa miR-204 and miR-4331 Negatively Regulate Swine H1N1/2009 Influenza A Virus Replication by Targeting Viral HA and NS, Respectively

tetano

Editor, Senior Moderator
Int J Mol Sci. 2017 Apr 3;18(4). pii: E749. doi: 10.3390/ijms18040749.
[h=1]Sus scrofa miR-204 and miR-4331 Negatively Regulate Swine H1N1/2009 Influenza A Virus Replication by Targeting Viral HA and NS, Respectively.[/h] Zhang S[SUP]1[/SUP], Wang R[SUP]2[/SUP], Su H[SUP]3[/SUP], Wang B[SUP]4[/SUP], Sizhu S[SUP]5[/SUP], Lei Z[SUP]6[/SUP], Jin M[SUP]7,[/SUP][SUP]8[/SUP], Chen H[SUP]9,[/SUP][SUP]10[/SUP], Cao J[SUP]11[/SUP], Zhou H[SUP]12,[/SUP][SUP]13[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] The prevalence of swine pandemic H1N1/2009 influenza A virus (SIV-H1N1/2009) in pigs has the potential to generate novel reassortant viruses, posing a great threat to human health. Cellular microRNAs (miRNAs) have been proven as promising small molecules for regulating influenza A virus replication by directly targeting viral genomic RNA. In this study, we predicted potential Sus scrofa (ssc-, swine) miRNAs targeting the genomic RNA of SIV-H1N1/2009 by RegRNA 2.0, and identified ssc-miR-204 and ssc-miR-4331 to target viral HA and NS respectively through dual-luciferase reporter assays. The messenger RNA (mRNA) levels of viral HA and NS were significantly suppressed when newborn pig trachea (NPTr) cells respectively overexpressed ssc-miR-204 and ssc-miR-4331 and were infected with SIV-H1N1/2009, whereas the suppression effect could be restored when respectively decreasing endogenous ssc-miR-204 and ssc-miR-4331 with inhibitors. Because of the importance of viral HA and NS in the life cycle of influenza A virus, ssc-miR-204 and ssc-miR-4331 exhibited an inhibition effect on SIV-H1N1/2009 replication. The antiviral effect was sequence-specific of SIV-H1N1/2009, for the target sites in HA and NS of H5N1 or H9N2 influenza A virus were not conserved. Furthermore, SIV-H1N1/2009 infection reversely downregulated the expression of ssc-miR-204 and ssc-miR-4331, which might facilitate the virus replication in the host. In summary, this work will provide us some important clues for controlling the prevalence of SIV-H1N1/2009 in pig populations.


[h=4]KEYWORDS:[/h] RegRNA 2.0; Sus scrofa miR-204; Sus scrofa miR-4331; miRNA-virus interaction; viral genomic RNA; virus replication

PMID: 28368362 DOI: 10.3390/ijms18040749
 
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