New insights into the evolution of IFNs: zebrafish Group II IFNs induce a rapid and transient expression of IFN-dependent genes and display powerful antiviral activities

López-Muñoz, A., Roca, F.J., Meseguer, J., and Mulero, V.
Journal of immunology (Baltimore, Md. : 1950)   182(6): 3440-3449 (Journal)
Registered Authors
Mulero, Victor
MeSH Terms
  • Animals
  • Antiviral Agents/administration & dosage*
  • Antiviral Agents/classification
  • Antiviral Agents/metabolism
  • Cell Line
  • Evolution, Molecular*
  • Gene Expression Profiling*
  • Gene Expression Regulation, Viral/immunology*
  • Humans
  • Inflammation Mediators/administration & dosage
  • Inflammation Mediators/classification
  • Inflammation Mediators/physiology
  • Interferon Type I/administration & dosage
  • Interferon Type I/physiology
  • Interferon-gamma/administration & dosage
  • Interferon-gamma/genetics
  • Interferon-gamma/physiology*
  • Rhabdoviridae Infections/genetics
  • Rhabdoviridae Infections/immunology
  • Rhabdoviridae Infections/metabolism
  • Streptococcal Infections/genetics
  • Streptococcal Infections/immunology
  • Streptococcal Infections/metabolism
  • Vesiculovirus/immunology*
  • Viremia/genetics
  • Viremia/immunology
  • Viremia/metabolism
  • Zebrafish
  • Zebrafish Proteins/administration & dosage
  • Zebrafish Proteins/biosynthesis*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/physiology
19265122 Full text @ J. Immunol.
The IFNs and their receptors have existed in early chordates for approximately 500 million years and represent the early elements in innate and adaptive immunity. Both types I and II IFNs have been discovered in fish, and type I has recently been classified into two groups based on their primary protein sequences. However, the biological activities of fish IFNs and their roles in infection are largely unknown. Using the zebrafish and manageable bacterial (Streptococcus iniae) and viral (spring viremia of carp virus) infection models, we are reporting in this study that zebrafish IFN (zfIFN) gamma failed to induce antiviral and proinflammatory genes when administered in vivo, which correlates with its inability to protect the fish against bacterial and viral infections. We also found that, although both group I (i.e., zfIFN1) and group II zfIFNs (i.e., zfIFN2 and zfIFN3) displayed strong in vivo antiviral activities, only group I zfIFN was able to protect the fish against bacterial infection, which may reflect the different patterns and kinetics of immune-related genes elicited by these two groups of IFNs. Thus, group II zfIFNs induced a rapid and transient expression of antiviral genes, whereas group I zfIFN exerted a slow but more powerful induction of several antiviral and proinflammatory genes. Collectively, our results suggest nonredundant, complementary roles of type I zfIFNs in viral infections and provide evidence for a pivotal role of the recently identified group II IFN of fish in the early stages of viral infections.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes