The dengue virus nonstructural-1 protein (NS1) generates antibodies to common epitopes on human blood clotting, integrin/adhesin proteins and binds to human endothelial cells: potential implications in haemorrhagic fever pathogenesis

Arch Virol. 1997;142(5):897-916. doi: 10.1007/s007050050127.

Abstract

Antibody responses generated by mice to the dengue-2 virus NS1 protein (D-2V NS1) were influenced by MHC class II (I-A) haplotype but each antiserum cross-reacted with human fibrinogen, thrombocytes and endothelial cells. To investigate these findings, a highly avid subclone (MAb 1G5.4-A1-C3) was selected from a parent hybridoma that secreted a monoclonal antibody (MAb) specific for the native dimeric form of D-2V NS1. When MAb reactions were compared using a panel of overlapping synthetic peptides covering the entire protein sequence, dimer specificity was found to be a weak reaction with multiple ELK-type motifs present in either the positive (E/D-hydrophobic-K/R) or negative (K/R-hydrophobic-D/E) orientations. MAb 1G5.4-A1-C3 and highly avid anti-NS1 polyclonal antisera reacted with the NS1 proteins of the four dengue virus serotypes, but only weakly reacted with the NS1 proteins of the other flaviviruses. MAb 1G5.4-A1-C3 and several other anti-NS1 MAbs produced haemorrhage in mice, cross-reacted with human fibrinogen, thrombocytes and endothelial cells, with known epitopes or active sites on human clotting factors and integrin/adhesin proteins present on these cells. D-2V NS1 bound to human endothelial cells via a site within its N-terminal region, which led to significantly increased binding of avid anti-NS1 antibodies. These results identified a potential role of both 'antigenic' and 'biochemical' mimicry in dengue haemorrhagic fever pathogenesis, consistent with clinical data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Antibody Formation*
  • Antigens, Viral / immunology*
  • Blood Platelets / immunology
  • Cross Reactions
  • Dengue / immunology*
  • Dengue Virus / immunology*
  • Endothelium, Vascular / immunology*
  • Epitopes / immunology*
  • Fibrinogen / immunology*
  • Humans
  • Integrins / immunology*
  • Mice
  • Viral Nonstructural Proteins / immunology*

Substances

  • Antibodies, Monoclonal
  • Antigens, Viral
  • Epitopes
  • Integrins
  • NS1 protein, Dengue virus type 2
  • Viral Nonstructural Proteins
  • Fibrinogen