The negative regulation of piscine CD44c in viral and bacterial infection

Dev Comp Immunol. 2019 Jul;96:135-143. doi: 10.1016/j.dci.2019.03.005. Epub 2019 Mar 15.

Abstract

CD44 gene is a cell surface receptor which undergoes complex alternative splicing and extensive post-translational modifications. Although many studies have showed that CD44 is involved in the process of host defense, the function of piscine CD44 in antibacterial or antiviral defense response remains unclear. In the present study, we report the functional characterization of zebrafish CD44c, which is more similar to CD44b antigen isoforms rather than CD44a based on amino acid composition and phylogenetic analysis. The expression of zebrafish CD44c was inducible in response to bacterial and viral infections. During SVCV infection, the in vivo studies revealed that CD44c overexpression led to the increased virus loads and decreased survival rate. The attenuated response by zebrafish CD44c in response to SVCV infection were characterized by the impaired production of inflammatory cytokines and the impaired expressions of IFNs, IFN-stimulated genes, MHC class I and II genes. During Edwardsiella piscicida infection, the overexpression of zebrafish CD44c facilitated bacterial growth and dissemination, but did not impact on larvae survival. The detrimental role of CD44c in host defense against E. piscicida infection was supported by a decreased production of several antibacterial molecules including defbl2, defbl3, NK-lysin and RNase3. All together, these results firstly demonstrate the negative regulation of piscine CD44c in viral and bacterial infection.

Keywords: Antibacterial molecules; Antiviral genes; Bacterial infection; Inflammatory cytokines; MHC genes; Negative regulation; Viral infection; Zebrafish CD44.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / immunology
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cytokines / immunology
  • Cytokines / metabolism
  • Edwardsiella / immunology
  • Edwardsiella / pathogenicity
  • Enterobacteriaceae Infections / immunology*
  • Enterobacteriaceae Infections / microbiology
  • Fish Diseases / immunology*
  • Fish Diseases / microbiology
  • Hyaluronan Receptors / chemistry
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / immunology*
  • Immunity, Innate
  • Larva / immunology
  • Larva / metabolism
  • Phylogeny
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / immunology
  • Rhabdoviridae / immunology
  • Rhabdoviridae / pathogenicity
  • Rhabdoviridae Infections / immunology*
  • Rhabdoviridae Infections / virology
  • Structure-Activity Relationship
  • Zebrafish / genetics
  • Zebrafish / immunology*
  • Zebrafish / metabolism
  • Zebrafish / virology

Substances

  • Cytokines
  • Hyaluronan Receptors
  • Protein Isoforms

Supplementary concepts

  • Carp sprivivirus