Molecular Therapy: Nucleic Acids (Sep 2019)

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

Journal volume & issue
Vol. 17
pp. 10 – 23

Abstract

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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. Keywords: influenza A virus, miR-1290, vimentin, viral ribonucleoprotein, vRNP, miRNA, virus, host species-specificity, ferret