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

Sheng Yu Huang, Chih Heng Huang, Chi Jene Chen, Ting-Wen Chen, Chun Yuan Lin, Yueh Te Lin, Shu Ming Kuo, Chung Guei Huang, Li Ang Lee, Yi Hsiang Chen, Mei Feng Chen, Rei Lin Kuo, Shin Ru Shih*

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)10-23
Number of pages14
JournalMolecular Therapy - Nucleic Acids
Volume17
DOIs
StatePublished - 6 Sep 2019

Keywords

  • ferret
  • host species-specificity
  • influenza A virus
  • miR-1290
  • miRNA
  • vRNP
  • vimentin
  • viral ribonucleoprotein
  • virus

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  • Cite this

    Huang, S. Y., Huang, C. H., Chen, C. J., Chen, T-W., Lin, C. Y., Lin, Y. T., Kuo, S. M., Huang, C. G., Lee, L. A., Chen, Y. H., Chen, M. F., Kuo, R. L., & Shih, S. R. (2019). Novel Role for miR-1290 in Host Species Specificity of Influenza A Virus. Molecular Therapy - Nucleic Acids, 17, 10-23. https://doi.org/10.1016/j.omtn.2019.04.028