Novel Role for miR-1290 in Host Species Specificity of Influenza A Virus

• Published in: Molecular therapy. Nucleic acids 2019-09, Vol.17, p.10-23
• Main Authors: Huang, Sheng-Yu, Huang, Chih-Heng, Chen, Chi-Jene, Chen, Ting-Wen, Lin, Chun-Yuan, Lin, Yueh-Te, Kuo, Shu-Ming, Huang, Chung-Guei, Lee, Li-Ang, Chen, Yi-Hsiang, Chen, Mei-Feng, Kuo, Rei-Lin, Shih, Shin-Ru
• Format: Article
• Language: English
• Subjects: Animal models; Binding sites; Cell culture; Experiments; Extracellular signal-regulated kinase; ferret; Gene expression; host species-specificity; Infections; Influenza; Influenza A; influenza A virus; Mammals; Metabolic pathways; MicroRNAs; miR-1290; miRNA; Proteins; Species; Statistical analysis; Vimentin; Viral infections; viral ribonucleoprotein; virus; Viruses; vRNP
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2019.04.028

The role of microRNA (miRNA) in influenza A virus (IAV) host species specificity is not well understood as yet. Here, we show that a host miRNA, miR-1290, is induced through the extracellular signal-regulated kinase (ERK) pathway upon IAV infection and is associated with increased viral titers in human cells and ferret animal models. miR-1290 was observed to target and reduce expression of the host vimentin gene. Vimentin binds with the PB2 subunit of influenza A virus ribonucleoprotein (vRNP), and knockdown of vimentin expression significantly increased vRNP nuclear retention and viral polymerase activity. Interestingly, miR-1290 was not detected in either chicken cells or mouse animal models, and the 3′ UTR of the chicken vimentin gene contains no binding site for miR-1290. These findings point to a host species-specific mechanism by which IAV upregulates miR-1290 to disrupt vimentin expression and retain vRNP in the nucleus, thereby enhancing viral polymerase activity and viral replication. [Display omitted]