Antibodies to dengue 2 virus E-glycoprotein synthetic peptides identify antigenic conformation

Abstract

Eighteen synthetic peptides have now been prepared from dengue (DEN) 2 virus, representing 80% of the extramembranal domain of the DEN envelope (E)-glycoprotein. These peptides were selected based upon our previous results with Murray Valley encephalitis (MVE) virus, computer analysis of the DEN virus sequence, and the predicted E-glycoprotein secondary structure. Six of these peptides were “structural” peptides derived from either nonlinear amino acid sequences or predicted disulfide bridge-stabilized loop structures. As with MVE virus, some peptides could be recognized by antivirus hyperimmune ascitic fluids, but monoclonal antiflavivirus antibodies failed to react with any peptide. Immunogenicity of these peptides was tested in BALB/c or NIH-Swiss mice. Fourteen of these peptides elicited antipeptide antibody in one or both mouse strains. Eleven of these antipeptides reacted with virus. Peptides 35 (amino acids 35–55) and 17 (amino acids 352–368) elicited virus-neutralizing antibody. Four antipeptides were more efficient at binding to pH 5.0-treated virus. These antipeptides precisely defined a flavivirus group common sequence (amino acids 98–110) that has biochemical characteristics similar to previously defined viral fusion sequences.