Epitopes on the dengue 1 virus envelope protein recognized by neutralizing IgM monoclonal antibodies.
Three of 41 IgM monoclonal antibodies derived from dengue 1 virus immunized mice neutralized dengue 1 infection in vitro. All three neutralizing monoclonal antibodies reacted with spatially related epitopes on the E protein of dengue 1 which were also recognized by antibodies in sera from dengue patients. Two neutralization-resistant populations of dengue 1 virus, D1-M10 and D1-M17, were selected by sequential passage of virus in C6/36 cells in the presence of neutralizing IgM monoclonal antibodies M10 and M17, respectively. Single nucleotide changes occurred in the E protein gene of each of these virus populations resulting in single amino acid substitutions at E279 (Phe-Ser) in D1-M10 and at E293 (Thr-Ile) in D1-M17. Both neutralization-resistant populations of virus were more sensitive to elevated temperature than was the wild-type dengue 1 virus and the infectivity and haemagglutinating ability of the neutralization-resistant populations decreased more slowly than that of wild-type virus when exposed to pH in the range 5.8 to 7.0. These are the first epitopes involved in neutralization to have been identified in dengue 1 virus and the first outside domain III of the E protein on any dengue virus.
Beasley
D W
DW
Centre for Molecular Biotechnology, School of Life Sciences, Queensland University of Technology, 2 George Street, Brisbane, Queensland, 4000, Australia.
Aaskov
J G
JG
D019943:Amino Acid Substitution; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D003716:Dengue Virus / Q000276:immunology* / Q000472:pathogenicity; D000939:Epitopes / Q000276:immunology; D006389:Hemagglutinins, Viral / Q000032:analysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007106:Immune Sera; D007075:Immunoglobulin M / Q000276:immunology*; D051379:Mice; D008961:Models, Structural; D009154:Mutation; D009500:Neutralization Tests; D013696:Temperature; D014759:Viral Envelope Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D006389:Hemagglutinins, Viral; D007106:Immune Sera; D007075:Immunoglobulin M; D014759:Viral Envelope Proteins; C072281:E protein TH Sman, Dengue virus