Exploitation of Host Species-Specific miR-1290-Vimentin Axis Regulation by Influenza A Virus

• Main Authors: Sheng Yu Huang, 黃聖愉
• Other Authors: S. R. Shih
• Format: Others
• Language: en_US
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/cgi-bin/gs32/gsweb.cgi/login?o=dnclcdr&s=id=%22107CGU05114030%22.&searchmode=basic

博士 === 長庚大學 === 生物醫學研究所 === 107 === The role of microRNA (miRNA) in influenza A virus (IAV) host species-specificity is not well understood as yet. Here we describe a novel role for miR-1290, a host miRNA expressed in humans and ferrets, but not chickens or mice. We show that miR-1290 is induced through the 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 the expression of the host vimentin gene. Vimentin bound to the PB2 subunit of IAV ribonucleoprotein (vRNP), and knockdown of vimentin expression significantly increased vRNP nuclear retention and viral polymerase activity. Interestingly, miR-1290 could not be detected in either chicken cells or mouse animal models, and the 3’ untranslated region (UTR) of the chicken vimentin gene does not contain binding sites for miR-1290. The introduction of a miR-1290 binding site into the chicken vimentin 3’UTR subsequently allowed the target of miR-1290 to target and reduced expression of chicken vimentin. 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.