Epitopes on the dengue 1 virus envelope protein recognized by neutralizing IgM monoclonal antibodies

David W.C. Beasley, John G. Aaskov

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)447-458
Number of pages12
JournalVirology
Volume279
Issue number2
DOIs
StatePublished - Jan 15 2001

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Keywords

  • Dengue virus
  • Neutralization escape mutant
  • Neutralizing epitopes

ASJC Scopus subject areas

  • Virology

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