tetano
Editor, Senior Moderator
Cell Microbiol. 2019 Jan 16:e13001. doi: 10.1111/cmi.13001. [Epub ahead of print]
[h=1]miR-193b represses influenza A virus infection by inhibiting Wnt/β-catenin signaling.[/h] Yang X[SUP]1,[/SUP][SUP]2[/SUP], Zhao C[SUP]2[/SUP], Bamunuarachchi G[SUP]1,[/SUP][SUP]2[/SUP], Wang Y[SUP]2[/SUP], Liang Y[SUP]1,[/SUP][SUP]2[/SUP], Huang C[SUP]1,[/SUP][SUP]2[/SUP], Zhu Z[SUP]1,[/SUP][SUP]2[/SUP], Xu D[SUP]1,[/SUP][SUP]2[/SUP], Lin K[SUP]1,[/SUP][SUP]2[/SUP], Senavirathna LK[SUP]1,[/SUP][SUP]2[/SUP], Xu L[SUP]2[/SUP], Liu L[SUP]1,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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
[h=1]miR-193b represses influenza A virus infection by inhibiting Wnt/β-catenin signaling.[/h] Yang X[SUP]1,[/SUP][SUP]2[/SUP], Zhao C[SUP]2[/SUP], Bamunuarachchi G[SUP]1,[/SUP][SUP]2[/SUP], Wang Y[SUP]2[/SUP], Liang Y[SUP]1,[/SUP][SUP]2[/SUP], Huang C[SUP]1,[/SUP][SUP]2[/SUP], Zhu Z[SUP]1,[/SUP][SUP]2[/SUP], Xu D[SUP]1,[/SUP][SUP]2[/SUP], Lin K[SUP]1,[/SUP][SUP]2[/SUP], Senavirathna LK[SUP]1,[/SUP][SUP]2[/SUP], Xu L[SUP]2[/SUP], Liu L[SUP]1,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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