Higher antiviral response of RIG-I through enhancing RIG-I/MAVS-mediated signaling by its long insertion variant in zebrafish

Zou, P.F., Chang, M.X., Li, Y., Zhang, S.H., Fu, J.P., Chen, S.N., Nie, P.
Fish & shellfish immunology   43(1): 13-24 (Journal)
Registered Authors
Chang, Mingxian, Li, Ying, Nie, Pin
RIG-Ib/MAVS-mediated signaling pathway, mitochondrial antiviral signaling protein, retinoic acid-inducible gene-I, type I IFN production, variant
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Antiviral Agents/metabolism
  • Cell Line
  • Cloning, Molecular
  • DNA, Complementary/genetics
  • DNA, Complementary/metabolism
  • Edwardsiella tarda/physiology
  • Enterobacteriaceae Infections/genetics
  • Enterobacteriaceae Infections/metabolism
  • Enterobacteriaceae Infections/veterinary*
  • Enterobacteriaceae Infections/virology
  • Fish Diseases/genetics*
  • Fish Diseases/metabolism
  • Fish Diseases/virology
  • Gene Expression Regulation*
  • Interferon Type I/genetics
  • Interferon Type I/metabolism
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Rhabdoviridae/physiology
  • Rhabdoviridae Infections/genetics
  • Rhabdoviridae Infections/metabolism
  • Rhabdoviridae Infections/veterinary*
  • Rhabdoviridae Infections/virology
  • Sequence Alignment/veterinary
  • Signal Transduction*
  • Zebrafish*
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
25524497 Full text @ Fish Shellfish Immunol.
As an intracellular pattern recognition receptor (PRR), the retinoic acid-inducible gene-I (RIG-I) is responsible for the recognition of cytosolic viral nucleic acids and the production of type I interferons (IFNs). In the present study, an insertion variant of RIG-I with 38 amino acids inserted in the N-terminal CARD2 domain, as well as the typical type, named as RIG-Ia and RIG-Ib respectively were identified in zebrafish. RIG-Ia and RIG-Ib were all up-regulated following the infection of a negative ssRNA virus, the Spring Viremia of Carp Virus (SVCV), and an intracellular Gram-negative bacterial pathogen Edwardsiella tarda, indicating the RLR may have a role in the recognition of both viruses and bacteria. The over-expression of RIG-Ib in cultured fish cells resulted in significant increase in type I IFN promoter activity, and in protection against SVCV infection, whereas the over-expression of RIG-Ia had no direct effect on IFN activation nor antiviral response. Furthermore, it was revealed that both RIG-Ia and RIG-Ib were associated with the downstream molecular mitochondrial antiviral signaling protein, MAVS, and interestingly RIG-Ia when co-transfected with RIG-Ib or MAVS, induced a significantly higher level of type I IFN promoter activity and the expression level of Mx and IRF7, implying that the RIG-Ia may function as an enhancer in the RIG-Ib/MAVS-mediated signaling pathway.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes