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miR-193b represses influenza A virus infection by inhibiting Wnt/β-catenin signaling

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  • miR-193b represses influenza A virus infection by inhibiting Wnt/β-catenin signaling

    Cell Microbiol. 2019 Jan 16:e13001. doi: 10.1111/cmi.13001. [Epub ahead of print]
    miR-193b represses influenza A virus infection by inhibiting Wnt/β-catenin signaling.

    Yang X1,2, Zhao C2, Bamunuarachchi G1,2, Wang Y2, Liang Y1,2, Huang C1,2, Zhu Z1,2, Xu D1,2, Lin K1,2, Senavirathna LK1,2, Xu L2, Liu L1,2.
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    Abstract

    Due to an increasing emergence of new and drug-resistant strains of the influenza A virus (IAV), developing novel measures to combat influenza is necessary. We have previously shown that inhibiting Wnt/β-catenin pathway reduces IAV infection. In this study, we aimed to identify antiviral human microRNAs (miRNAs) that target the Wnt/β-catenin signaling pathway. Using a miRNA expression library, we identified 85 miRNAs that upregulated and 20 miRNAs that downregulated the Wnt/β-catenin signaling pathway. Fifteen miRNAs were validated to upregulate and 5 miRNAs to downregulate the pathway. Overexpression of 4 selected miRNAs (miR-193b, miR-548f-1, miR-1-1 and miR-509-1) that downregulated the Wnt/β-catenin signaling pathway reduced viral mRNA, protein levels in A/PR/8/34-infected HEK293 cells and progeny virus production. Overexpression of miR-193b in lung epithelial A549 cells also resulted in decreases of A/PR/8/34 infection. Furthermore, miR-193b inhibited the replication of various strains, including H1N1 (A/PR/8/34, A/WSN/33, A/Oklahoma/3052/09) and H3N2 (A/Oklahoma/309/2006), as determined by a viral reporter luciferase assay. Further studies revealed that β-catenin was a target of miR-193b and β-catenin rescued miR-193b-mediated suppression of IAV infection. miR-193b induced G0/G1 cell cycle arrest and delayed vRNP nuclear import. Finally, adenovirus-mediated gene transfer of miR-193b to the lung reduced viral load in mice challenged by a sublethal dose of A/PR/8/34. Collectively, our findings suggest that miR-193b represses IAV infection by inhibiting Wnt/β-catenin signaling.
    This article is protected by copyright. All rights reserved.


    PMID: 30650225 DOI: 10.1111/cmi.13001
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