gga-miR-2127 downregulates the translation of chicken p53 and attenuates chp53-mediated innate immune response against IBDV infection

Vet Microbiol. 2017 Jan:198:34-42. doi: 10.1016/j.vetmic.2016.12.007. Epub 2016 Dec 6.

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.

Keywords: Antiviral innate immunity; Infectious bursal disease; chp53; gga-miR-2127; miRNA.

MeSH terms

  • Animals
  • Birnaviridae Infections / immunology
  • Birnaviridae Infections / veterinary*
  • Cell Line
  • Chick Embryo
  • Chickens / immunology
  • Down-Regulation*
  • Gene Expression Regulation / immunology
  • Host-Pathogen Interactions / genetics
  • Immune Tolerance / genetics
  • Immune Tolerance / immunology
  • Immunity, Innate / genetics*
  • Immunity, Innate / immunology
  • Infectious bursal disease virus / immunology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Poultry Diseases* / genetics
  • Poultry Diseases* / immunology
  • Tumor Suppressor Protein p53* / genetics
  • Tumor Suppressor Protein p53* / metabolism
  • Virus Replication / immunology

Substances

  • MicroRNAs
  • Tumor Suppressor Protein p53