PUBLICATION

Zebrafish HERC7c Acts as an Inhibitor of Fish IFN Response

Authors
Li, Y.L., Gong, X.Y., Qu, Z.L., Zhao, X., Dan, C., Sun, H.Y., An, L.L., Gui, J.F., Zhang, Y.B.
ID
ZDB-PUB-230312-45
Date
2023
Source
International Journal of Molecular Sciences   24(5): (Journal)
Registered Authors
Gui, Jian-Fang, Zhang, Yi-Bing
Keywords
HERC7 subfamily, IFN response, negative regulation, protein attenuation, small HERC family
MeSH Terms
  • Animals
  • Antiviral Agents
  • Fish Diseases*
  • Humans
  • Interferons/metabolism
  • Rhabdoviridae Infections*
  • Ubiquitins
  • Zebrafish/genetics
  • Zebrafish Proteins/metabolism
PubMed
36902023 Full text @ Int. J. Mol. Sci.
Abstract
In humans, four small HERCs (HERC3-6) exhibit differential degrees of antiviral activity toward HIV-1. Recently we revealed a novel member HERC7 of small HERCs exclusively in non-mammalian vertebrates and varied copies of herc7 genes in distinct fish species, raising a question of what is the exact role for a certain fish herc7 gene. Here, a total of four herc7 genes (named HERC7a-d sequentially) are identified in the zebrafish genome. They are transcriptionally induced by a viral infection, and detailed promoter analyses indicate that zebrafish herc7c is a typical interferon (IFN)-stimulated gene. Overexpression of zebrafish HERC7c promotes SVCV (spring viremia of carp virus) replication in fish cells and concomitantly downregulates cellular IFN response. Mechanistically, zebrafish HERC7c targets STING, MAVS, and IRF7 for protein degradation, thus impairing cellular IFN response. Whereas the recently-identified crucian carp HERC7 has an E3 ligase activity for the conjugation of both ubiquitin and ISG15, zebrafish HERC7c only displays the potential to transfer ubiquitin. Considering the necessity for timely regulation of IFN expression during viral infection, these results together suggest that zebrafish HERC7c is a negative regulator of fish IFN antiviral response.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping