1. gga-miR-9* inhibits IFN production in antiviral innate immunity by targeting interferon regulatory factor 2 to promote IBDV replication
- Author
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Xi-ning Du, Wei Ouyang, Yongshan Wang, Liu Huajie, and Haibin Zhang
- Subjects
Untranslated region ,Interferon Regulatory Factor 2 ,Biology ,Virus Replication ,Antiviral Agents ,Infectious bursal disease virus ,Microbiology ,Virus ,microRNA ,Animals ,Luciferases ,Poultry Diseases ,Gene knockdown ,Innate immune system ,General Veterinary ,General Medicine ,Birnaviridae Infections ,Virology ,Immunity, Innate ,MicroRNAs ,Gene Knockdown Techniques ,Host-Pathogen Interactions ,Interferon Type I ,Ectopic expression ,Chickens ,IRF2 ,Interferon Regulatory Factor-2 - 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.
- Published
- 2015
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