title: gga-miR-2127 downregulates the translation of chicken p53 and attenuates chp53-mediated innate immune response against IBDV infection.
abstract: Infectious bursal disease (IBD) is characterized by the immune suppression of infected birds. The molecular mechanism by which IBD virus (IBDV) suppresses the host immune system remains to be elucidated. The tumor suppressor protein p53 can inhibit the replication of various viruses, but its effect on IBDV remains unknown. This study established an in vitro infection model based on DF-1 cells (chicken embryo fibroblast cell line) to investigate the antiviral effects of chicken p53 (chp53) on IBDV infection. The expression level and activity of chp53 remarkably increased in IBDV-infected DF-1 cells. The overexpression of chp53 inhibited IBDV replication and upregulated the expression of multiple chicken antiviral innate immunity genes (IPS-1, IRF3, PKR, OAS, and Mx), whereas the suppression of chp53 led to the opposite effect. This result indicates that chp53 activates the antiviral innate immune response of chickens to IBDV infection. Bioinformatics analysis and dual-luciferase reporter assay showed that gga-miR-2127 targeted the 3'UTR of chp53. qRT-PCR and western blot revealed that gga-miR-2127 overexpression in DF-1 cells not only downregulated the expression levels of chp53 and of the antiviral innate immunity genes in chickens but also promoted IBDV replication. Our results suggest that gga-miR-2127 downregulates chp53 mRNA translation by targeting its 3'UTR and attenuates chp53-mediated antiviral innate immune response against IBDV.
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; First Affiliated Hospital with Nanjing Medical University/Jiangsu Province Hospital, Nanjing 210029, China; College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, 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@126.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; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses,Yangzhou 225009, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Meng
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.
authors.forename: Qun-Xing
authors.initials: QX
authors.lastname: Pan
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.
authors.forename: Xiao-Li
authors.initials: XL
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; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses,Yangzhou 225009, China.
authors.forename: Xing-Xia
authors.initials: XX
authors.lastname: Xia
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.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Zhu
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.
authors.forename: Zhen-Wei
authors.initials: ZW
authors.lastname: Bi
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Zhang
authors.affiliation: First Affiliated Hospital with Nanjing Medical University/Jiangsu Province Hospital, Nanjing 210029, China. Electronic address: nanjingluokai@hotmail.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Luo
mesh_terms: D000818:Animals; D018175:Birnaviridae Infections / Q000276:immunology / Q000662:veterinary*; D002460:Cell Line; D002642:Chick Embryo; D002645:Chickens / Q000276:immunology; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000235:genetics; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics* / Q000276:immunology; D007243:Infectious bursal disease virus / Q000276:immunology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011201:Poultry Diseases / Q000235:genetics / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000276:immunology
chemical_list: D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53
keywords: Antiviral innate immunity; Infectious bursal disease; chp53; gga-miR-2127; miRNA