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

doi:10.1016/j.omtn.2019.04.028

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

Mol Ther Nucleic Acids. 2019 Sep 6:17:10-23. doi: 10.1016/j.omtn.2019.04.028. Epub 2019 May 15.

Authors

Affiliations

¹ Graduate Institute of Biomedical Science, Division of Biotechnology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
² Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; The Institute of Microbiology and Immunology, National Defense Medical Center, Taipei 11490, Taiwan; The Institute of Preventive Medicine, National Defense Medical Center, Taipei 11490, Taiwan.
³ Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
⁴ Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu 30068, Taiwan; Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, 30068, Taiwan.
⁵ Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Department of Computer Science and Information Engineering, College of Engineering, Chang Gung University, Taoyuan 33302, Taiwan.
⁶ Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Department of Computer Science and Information Engineering, College of Engineering, Chang Gung University, Taoyuan 33302, Taiwan; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
⁷ Graduate Institute of Biomedical Science, Division of Biotechnology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan.
⁸ Department of Otorhinolaryngology-Head and Neck Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; Faculty of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
⁹ Graduate Institute of Biomedical Science, Division of Biotechnology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Taoyuan 33302, Taiwan.
¹⁰ Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan; Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan; Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan. Electronic address: srshih@mail.cgu.edu.tw.

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.

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