Epitopes described in "Type- and subcomplex-specific neutralizing antibodies against domain III of dengue virus type 2 envelope protein recognize adjacent epitopes."

Reference
Article Authors:Soila Sukupolvi-Petty; S Kyle Austin; Whitney E Purtha; Theodore Oliphant; Grant E Nybakken; Jacob J Schlesinger; John T Roehrig; Gregory D Gromowski; Alan D Barrett; Daved H Fremont; Michael S Diamond
Article Title:Type- and subcomplex-specific neutralizing antibodies against domain III of dengue virus type 2 envelope protein recognize adjacent epitopes.
Reference Detail
Reference ID:1007661
Abstract:Neutralization of flaviviruses in vivo correlates with the development of an antibody response against the viral envelope (E) protein. Previous studies demonstrated that monoclonal antibodies (MAbs) against an epitope on the lateral ridge of domain III (DIII) of the West Nile virus (WNV) E protein strongly protect against infection in animals. Based on X-ray crystallography and sequence analysis, an analogous type-specific neutralizing epitope for individual serotypes of the related flavivirus dengue virus (DENV) was hypothesized. Using yeast surface display of DIII variants, we defined contact residues of a panel of type-specific, subcomplex-specific, and cross-reactive MAbs that recognize DIII of DENV type 2 (DENV-2) and have different neutralizing potentials. Type-specific MAbs with neutralizing activity against DENV-2 localized to a sequence-unique epitope on the lateral ridge of DIII, centered at the FG loop near residues E383 and P384, analogous in position to that observed with WNV-specific strongly neutralizing MAbs. Subcomplex-specific MAbs that bound some but not all DENV serotypes and neutralized DENV-2 infection recognized an adjacent epitope centered on the connecting A strand of DIII at residues K305, K307, and K310. In contrast, several MAbs that had poor neutralizing activity against DENV-2 and cross-reacted with all DENV serotypes and other flaviviruses recognized an epitope with residues in the AB loop of DIII, a conserved region that is predicted to have limited accessibility on the mature virion. Overall, our experiments define adjacent and structurally distinct epitopes on DIII of DENV-2 which elicit type-specific, subcomplex-specific, and cross-reactive antibodies with different neutralizing potentials.
Date:2007
Reference Type:Literature
PubMed ID:17881453
Journal:J Virol
Journal Volume:81
Article Pages:12816-26
Journal ISSN:1098-5514
Article Chemical List:Antibodies, Monoclonal;Antibodies, Viral;E-glycoprotein, Dengue virus type 2;Epitopes;Viral Envelope Proteins
Article MeSH List:Animals; Antibodies, Monoclonal(immunology); Antibodies, Viral(immunology); Cross Reactions; Dengue Virus(immunology); Epitope Mapping; Epitopes(immunology); Neutralization Tests; Viral Envelope Proteins(immunology)
Curation Last Updated:2014-10-03 20:58:07