Functional analysis of dengue virus (DENV) type 2 envelope protein domain 3 type-specific and DENV complex-reactive critical epitope residues

Trevor J. Pitcher, Vanessa V. Sarathy, Kiyohiko Matsui, Gregory D. Gromowski, Claire Y.H. Huang, Alan D.T. Barrett

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The dengue virus (DENV) envelope protein domain 3 (ED3) is the target of potent virus neutralizing antibodies. The DENV-2 ED3 contains adjacent type-specific and DENV complex-reactive antigenic sites that are composed of a small number of residues that were previously demonstrated to be critical for antibody binding. Site-directed mutagenesis of a DENV-2 16681 infectious clone was used to mutate critical residues in the DENV-2 type-specific (K305A and P384A) and DENV complex-reactive (K310A) antigenic sites. The K305A mutant virus multiplied like the parent virus in mosquito and mammalian cells, as did the P384A mutant virus, which required a compensatory mutation (G330D) for viability. However, the K310A mutant virus could not be recovered. The DENV-2 type-specific critical residue mutations K305A and P384A+G330D reduced the ability of DENV-2 type-specific, but not DENV complex-reactive, mAbs to neutralize virus infectivity and this was directly correlated with mAb binding affinity to the rED3 mutants.

Original languageEnglish (US)
Pages (from-to)288-293
Number of pages6
JournalJournal of General Virology
Volume96
Issue number2
DOIs
StatePublished - Feb 1 2015

ASJC Scopus subject areas

  • Virology

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