Substitution of the precursor peptide prevents anti-prM antibody-mediated antibody-dependent enhancement of dengue virus infection

Virus Res. 2017 Feb 2:229:57-64. doi: 10.1016/j.virusres.2016.12.003. Epub 2016 Dec 6.

Abstract

Antibody-dependent enhancement (ADE) is currently considered as the mechanism underlying the pathogenesis of severe dengue disease. Many studies have shown that precursor (pr) peptide-specific antibodies do not efficiently neutralize infection but potently promote ADE of dengue virus (DENV) infection. To explore the effect of pr peptide substitution on neutralization and ADE of DENV infection, the rabbit anti-prM polyclonal antibodies (pAbs) and anti-JEVpr/DENV-M pAbs were prepared, and the neutralization and ADE of these two pAbs were further compared. Here, we report that both anti-JEVpr/DENV-M and anti-prM pAbs exhibited broad cross-reactivity and only partial neutralization with four DENV serotypes and immature DENV. Rabbit anti-prM pAbs showed a significant enhancement in a broad range of serum dilutions. However, there was no statistically significant difference in the enhancing activity of rabbit anti-JEVpr/DENV-M pAbs at various levels of dilution. These results demonstrate that anti-prM antibody-mediated ADE can be prevented by JEV pr peptide replacement. The present study contribute further to research on the pathogenesis of DENV infection.

Keywords: Anti-prM antibody; Antibody-dependent enhancement; Chimeric protein; Dengue virus; Pre-membrane; Precursor peptide.

MeSH terms

  • Aedes / cytology
  • Aedes / virology
  • Animals
  • Antibodies, Monoclonal / biosynthesis
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / chemistry*
  • Antibody-Dependent Enhancement*
  • Cell Line
  • Cell Line, Tumor
  • Cloning, Molecular
  • Cross Reactions
  • Dengue Virus / genetics
  • Dengue Virus / growth & development
  • Dengue Virus / immunology*
  • Encephalitis Virus, Japanese / genetics
  • Encephalitis Virus, Japanese / immunology
  • Epithelial Cells / immunology
  • Epithelial Cells / virology
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Humans
  • Peptides / genetics
  • Peptides / immunology
  • Protein Precursors / genetics
  • Protein Precursors / immunology*
  • Rabbits
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Severe Dengue / immunology
  • Severe Dengue / virology
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Peptides
  • Protein Precursors
  • Recombinant Proteins
  • Viral Envelope Proteins