Neutralization of viral infectivity by zebrafish c-reactive protein isoforms

Mol Immunol. 2017 Nov:91:145-155. doi: 10.1016/j.molimm.2017.09.005. Epub 2017 Sep 12.

Abstract

This work explores the unexpected in vivo and in vitro anti-viral functions of the seven c-reactive protein (crp1-7) genes of zebrafish (Danio rerio). First results showed heterogeneous crp1-7 transcript levels in healthy wild-type zebrafish tissues and organs and how those levels heterogeneously changed not only after bacterial but also after viral infections, including those in adaptive immunity-deficient rag1-/- mutants. As shown by microarray hybridization and proteomic techniques, crp2/CRP2 and crp5/CRP5 transcripts/proteins were among the most modulated during in vivo viral infection situations including the highest responses in the absence of adaptive immunity. In contrast crp1/CRP1/and crp7/CRP7 very often remained unmodulated. All evidences suggested that zebrafish crp2-6/CRP2-6 may have in vivo anti-viral activities in addition to their well known anti-bacterial and/or physiological functions in mammalians. Confirming those expectations, in vitro neutralization and in vivo protection against spring viremia carp virus (SVCV) infections were demonstrated by crp2-6/CRP2-6 using crp1-7 transfected and/or CRP1-7-enriched supernatant-treated fish cells and crp2-5-injected one-cell stage embryo eggs, respectively. All these findings discovered a crp1-7/CRP1-7 primitive anti-viral functional diversity.These findings may help to study similar functions on the one-gene-coded human CRP, which is widely used as a clinical biomarker for bacterial infections, tissue inflammation and coronary heart diseases.

Keywords: CRP; SVCV; VHSV; anti-viral neutralizing activity; c-reactive protein; microarrays; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • C-Reactive Protein* / genetics
  • C-Reactive Protein* / immunology
  • Fish Diseases* / genetics
  • Fish Diseases* / immunology
  • Fish Diseases* / virology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / immunology
  • Mutation
  • Protein Isoforms / genetics
  • Protein Isoforms / immunology
  • Rhabdoviridae / immunology*
  • Zebrafish* / genetics
  • Zebrafish* / immunology
  • Zebrafish* / virology

Substances

  • Homeodomain Proteins
  • Protein Isoforms
  • RAG-1 protein
  • C-Reactive Protein