title: gga-miR-9* inhibits IFN production in antiviral innate immunity by targeting interferon regulatory factor 2 to promote IBDV replication.
abstract: MicroRNAs (miRNAs) are small non-coding RNAs that contribute to the repertoire of host-pathogen interactions during viral infections. In the current study, miRNA analysis showed that a panel of microRNAs, including gga-miR-9*, were markedly upregulated in specific-pathogen-free (SPF) chickens upon infection with infectious bursal disease virus (IBDV); however, the biological function of gga-miR-9* during viral infection remains unknown. Using a TCID50 assay, it was found that ectopic expression of gga-miR-9* significantly promoted IBDV replication. In turn, gga-miR-9* negatively regulated IBDV-triggered type I IFN production, thus promoting IBDV replication in DF-1 cells. Bioinformatics analysis indicates that the 3' untranslated region (UTR) of interferon regulatory factor 2 (IRF2) has two putative binding sites for gga-miR-9*. Targeting of IRF2 3'UTR by gga-miR-9* was determined by luciferase assay. Functional overexpression of gga-miR-9*, using gga-miR-9* mimics, inhibited IRF2 mRNA and protein expression. Transfection of the gga-miR-9* inhibitor abolished the suppression of IRF2 protein expression. Furthermore, IRF2 knockdown mediated the enhancing effect of gga-miR-9* on the type I IFN-mediated antiviral response. These findings indicate that inducible gga-miR-9* feedback negatively regulates the host antiviral innate immune response by suppressing type I IFN production via targeting IRF2.
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences/Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture/National Center for Engineering Research of Veterinary Bio-products, Nanjing 210014, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ouyang
authors.affiliation: Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences/Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture/National Center for Engineering Research of Veterinary Bio-products, Nanjing 210014, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. Electronic address: wangys63@163.com.
authors.forename: Yong-shan
authors.initials: YS
authors.lastname: Wang
authors.affiliation: Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences/Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture/National Center for Engineering Research of Veterinary Bio-products, Nanjing 210014, China.
authors.forename: Xi-ning
authors.initials: XN
authors.lastname: Du
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences/Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture/National Center for Engineering Research of Veterinary Bio-products, Nanjing 210014, China.
authors.forename: Hua-jie
authors.initials: HJ
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. Electronic address: haibinzh@njau.edu.cn.
authors.forename: Hai-bin
authors.initials: HB
authors.lastname: Zhang
mesh_terms: D000818:Animals; D018175:Birnaviridae Infections / Q000276:immunology / Q000662:veterinary*; D002645:Chickens; D055785:Gene Knockdown Techniques / Q000662:veterinary; D054884:Host-Pathogen Interactions / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D007243:Infectious bursal disease virus / Q000235:genetics / Q000276:immunology*; D050836:Interferon Regulatory Factor-2 / Q000037:antagonists & inhibitors / Q000235:genetics; D007370:Interferon Type I / Q000037:antagonists & inhibitors*; D008156:Luciferases; D035683:MicroRNAs / Q000235:genetics / Q000494:pharmacology*; D011201:Poultry Diseases / Q000276:immunology* / Q000821:virology*; D014779:Virus Replication / Q000502:physiology
chemical_list: D050836:Interferon Regulatory Factor-2; D007370:Interferon Type I; D035683:MicroRNAs; D008156:Luciferases
keywords: Infectious bursal disease virus (IBDV); gga-miR-9*; miRNA; siRNA