A DN-mda5 transgenic zebrafish model demonstrates that Mda5 plays an important role in snakehead rhabdovirus resistance

Dev Comp Immunol. 2015 Aug;51(2):298-304. doi: 10.1016/j.dci.2015.01.006. Epub 2015 Jan 26.

Abstract

Melanoma Differentiation-Associated protein 5 (MDA5) is a member of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family, which is a cytosolic pattern recognition receptor that detects viral nucleic acids. Here we show an Mda5-dependent response to rhabdovirus infection in vivo using a dominant-negative mda5 transgenic zebrafish. Dominant-negative mda5 zebrafish embryos displayed an impaired antiviral immune response compared to wild-type counterparts that can be rescued by recombinant full-length Mda5. To our knowledge, we have generated the first dominant-negative mda5 transgenic zebrafish and demonstrated a critical role for Mda5 in the antiviral response to rhabdovirus.

Keywords: Antiviral; Danio rerio; Mda5; Rhabdovirus; Type I IFN; Zebrafish.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / immunology
  • DEAD-box RNA Helicases / metabolism*
  • Immunity, Active / genetics
  • Interferon Type I / metabolism
  • Mutation / genetics
  • Receptors, Pattern Recognition / genetics
  • Receptors, Pattern Recognition / immunology
  • Receptors, Pattern Recognition / metabolism*
  • Rhabdoviridae / immunology*
  • Rhabdoviridae Infections / immunology*
  • Transgenes / genetics
  • Viral Load / genetics
  • Zebrafish / immunology*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / immunology
  • Zebrafish Proteins / metabolism*

Substances

  • Interferon Type I
  • Receptors, Pattern Recognition
  • Zebrafish Proteins
  • MDA5 protein,zebrafish
  • DEAD-box RNA Helicases