PUBLICATION

Functional characterization of viral tumor necrosis factor receptors encoded by cyprinid herpesvirus 3 (CyHV3) genome

Authors
Yi, Y., Qi, H., Yuan, J., Wang, R., Weng, S., He, J., Dong, C.
ID
ZDB-PUB-150609-6
Date
2015
Source
Fish & shellfish immunology   45(2): 757-70 (Journal)
Registered Authors
Keywords
Apoptosis, Cyprinid herpesvirus 3 (CyHV3), Immune regulation, Koi herpesvirus (KHV), TNF receptor, Zebrafish embryos
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Carps
  • Cell Line
  • Female
  • Fish Diseases/genetics*
  • Fish Diseases/metabolism
  • Fish Diseases/virology
  • Gene Expression Regulation
  • Herpesviridae/genetics
  • Herpesviridae/physiology*
  • Herpesviridae Infections/genetics
  • Herpesviridae Infections/metabolism
  • Herpesviridae Infections/veterinary*
  • Herpesviridae Infections/virology
  • Male
  • Open Reading Frames
  • Receptors, Tumor Necrosis Factor, Member 14/chemistry
  • Receptors, Tumor Necrosis Factor, Member 14/genetics*
  • Receptors, Tumor Necrosis Factor, Member 14/metabolism
  • Receptors, Tumor Necrosis Factor, Type I/chemistry
  • Receptors, Tumor Necrosis Factor, Type I/genetics*
  • Receptors, Tumor Necrosis Factor, Type I/metabolism
  • Sequence Alignment/veterinary
  • Viral Proteins/chemistry
  • Viral Proteins/genetics*
  • Viral Proteins/metabolism
  • Zebrafish*
PubMed
26052019 Full text @ Fish Shellfish Immunol.
Abstract
Cyprinid herpesvirus 3 (CyHV3) is a large double-stranded DNA virus of Alloherpesviridae family in the order Herpesvirales. It causes significant morbidity and mortality in common carp and its ornamental koi variety, and threatens the aquaculture industries worldwide. Mimicry of cytokines and cytokine receptors is a particular strategy for large DNA viruses in modulating the host immune response. Here, we report the identification and characterization of two novel viral homologues of tumor necrosis factor receptor (TNFR) encoded by CyHV3-ORF4 and -ORF12, respectively. CyHV3-ORF4 was identified as a homologue of HVEM and CyHV3-ORF12 as a homologue of TNFRSF1. Overexpression of ORF4 and ORF12 in zebrafish embryos results in embryonic lethality, morphological defects and increased apoptosis. Although we failed to identify any interaction between the two vTNFRs and their potential ligands in zebrafish TNF superfamily by yeast two-hybrid system, the expression of some genes in TNF superfamily or TNFR superfamily were mis-regulated in ORF4 or ORF12-overexpressing embryos, especially the death receptor zHDR and its cognate ligand DL1b. Further studies showed that the apoptosis induced by the both CyHV3 vTNFRs is mainly activated through the intrinsic apoptotic pathway and requires the crosstalk between the intrinsic and extrinsic apoptotic pathway. Additionally, using RT-qPCR and Western blot assays, the expression patterns of the both vTNFRs were also analyzed during CyHV3 productive infection. Collectively, this is the first functional study of two unique vTNFRs encoded by a herpesvirus infecting non-mammalian vertebrates, which may provide novel insights into viral immune regulation mechanism and the pathogenesis of CyHV3 infection.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping