A highly conserved region between amino acids 221 and 266 of dengue virus non-structural protein 1 is a major epitope region in infected patients

Am J Trop Med Hyg. 2014 Jul;91(1):146-55. doi: 10.4269/ajtmh.13-0624. Epub 2014 Apr 28.

Abstract

The immune response to dengue virus (DENV) infection generates high levels of antibodies (Abs) against the DENV non-structural protein 1 (NS1), particularly in cases of secondary infection. Therefore, anti-NS1 Abs may play a role in severe dengue infections, possibly by interacting (directly or indirectly) with host factors or regulating virus production. If it does play a role, NS1 may contain epitopes that mimic those epitopes of host molecules. Previous attempts to map immunogenic regions within DENV-NS1 were undertaken using mouse monoclonal Abs (MAbs). The aim of this study was to characterize the epitope regions of nine anti-NS1 human monoclonal Abs (HuMAbs) derived from six patients secondarily infected with DENV-2. These anti-NS1 HuMAbs were cross-reactive with DENV-1, -2, and -3 but not DENV-4. All HuMAbs bound a common epitope region located between amino acids 221 and 266 of NS1. This study is the first report to map a DENV-NS1 epitope region using anti-DENV MAbs derived from patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / biosynthesis
  • Antigens, Viral / chemistry
  • Antigens, Viral / immunology*
  • Conserved Sequence
  • Dengue / immunology*
  • Dengue / virology
  • Dengue Virus / classification
  • Dengue Virus / genetics
  • Dengue Virus / immunology*
  • Epitopes / chemistry
  • Epitopes / immunology*
  • Gene Expression
  • Host-Pathogen Interactions
  • Humans
  • Mice
  • Molecular Sequence Data
  • Peptide Mapping
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Serotyping
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / immunology*

Substances

  • Antibodies, Monoclonal
  • Antigens, Viral
  • Epitopes
  • NS1 protein, Dengue virus type 2
  • NS1 protein, Dengue virus type 3
  • NS1 protein, dengue-1 virus
  • Recombinant Proteins
  • Viral Nonstructural Proteins