MicroRNA-9-1 Attenuates Influenza A Virus Replication via Targeting Tankyrase 1

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Influenza A virus (IAV) resistance to antiviral drugs necessitates novel therapeutic targets.
• Host factors crucial for viral replication are potential targets for new antiviral therapies.

Purpose of the Study:

• To investigate the roles of tankyrase 1 (TNKS1) and miR-9-1 in IAV infection.
• To explore the potential of targeting TNKS1 and miR-9-1 for novel antiviral strategies.

Main Methods:

• Assessed TNKS1 expression in IAV-infected human lung epithelial cells and mouse lungs.
• Utilized RNA interference for TNKS1 knockdown and evaluated its effect on viral replication.
• Employed TNKS1 3'-untranslated region (3'-UTR) reporter assays to identify targeting microRNAs.
• Overexpressed miR-9-1 in lung epithelial cells and mouse lungs to assess its antiviral effects.
• Measured viral mRNA, protein levels, and virus production to quantify replication.

Main Results:

• Increased TNKS1 expression was observed in IAV-infected cells and tissues.
• TNKS1 knockdown significantly repressed influenza viral replication.
• miR-9-1 was identified as a microRNA targeting TNKS1.
• Overexpression of miR-9-1 reduced viral replication, induced type I interferon production, and enhanced STAT1 phosphorylation.
• Ectopic expression of miR-9-1 in mouse lungs inhibited viral replication and reduced susceptibility to IAV infection.

Conclusions:

• miR-9-1 acts as an anti-influenza microRNA by targeting TNKS1.
• miR-9-1 enhances the cellular antiviral state through type I interferon induction and STAT1 activation.
• Targeting the miR-9-1/TNKS1 axis presents a promising strategy for developing novel influenza antiviral therapies.