PUBLICATION

Zebrafish ARRDC3a negatively regulates type I IFN production by targeting the RLR signaling pathway

Authors
Shi, Y., Chen, K., Yan, H., Wang, J., Zou, J., Lu, Y.
ID
ZDB-PUB-250524-10
Date
2025
Source
Fish & shellfish immunology : 110430110430 (Journal)
Registered Authors
Keywords
ARRDC3a, RLR signaling pathway, SVCV, Zebrafish, type I IFN
MeSH Terms
  • Immunity, Innate*/genetics
  • Fish Diseases*/immunology
  • Phylogeny
  • Sequence Alignment/veterinary
  • Gene Expression Regulation*/immunology
  • Interferon Type I*/genetics
  • Interferon Type I*/immunology
  • Amino Acid Sequence
  • Animals
  • Zebrafish Proteins*/chemistry
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/immunology
  • Signal Transduction*/immunology
  • Zebrafish*/genetics
  • Zebrafish*/immunology
  • Rhabdoviridae Infections/immunology
  • Rhabdoviridae Infections/veterinary
  • Rhabdoviridae/physiology
PubMed
40409698 Full text @ Fish Shellfish Immunol.
Abstract
Arrestin domain-containing 3 (ARRDC3), a member of the α-arrestins family, plays an important regulatory role in host anti-tumor and cellular metabolism by modulating the degradation and transportation of G protein-coupled receptors (GPCRs). However, the function of ARRDC3 in fish remains largely unexplored, particularly in host antiviral response. Here, we identified a paralog of ARRDC3 in teleost, zebrafish ARRDC3a, which was found to be induced by spring viremia of carp virus (SVCV) in vivo and in vitro. Overexpression of ARRDC3a significantly attenuated IFN expression and facilitated SVCV replication, whereas its knockdown inhibited viral proliferation. Furthermore, ARRDC3a overexpression markedly suppressed the IFN response triggered by retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) signaling pathway, and reduced the protein stability of TBK1, MITA, and IRF3. In summary, our findings suggest that zebrafish ARRDC3a acts as a negative regulator of type I IFN production by targeting RLR-associated signaling molecules, thereby promoting SVCV replication in the host. Our study provides novel insights into the biological function of ARRDC3a in fish.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping