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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.
    Author information

    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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