Antibody Recognition and Neutralization Determinants on Domains I and II of West Nile Virus Envelope Protein

• DOI: 10.1128/jvi.01732-06
• Publication Date: 2006-11-27T23:43:39Z
• Authors: Theodore Oliphant; Grant E. Nybakken; Michael Engle; Qing Xu; Christopher A. Ne...; Soila Sukupolvi-P...; Anantha Marri; Bat-El Lachmi; Udy Olshevsky; Daved H. Fremont; Theodore C. Pierson; Michael S. Diamond
• Keywords: Epitope mapping

Previous studies have demonstrated that monoclonal antibodies (MAbs) against an epitope on the lateral surface of domain III (DIII) West Nile virus (WNV) envelope (E) strongly protect infection in animals. Herein, we observed significantly less efficient neutralization by 89 MAbs recognized I (DI) or II (DII) WNV E protein. Moreover, cells expressing Fc gamma receptors, many DI- and DII-specific enhanced over a broad range concentrations. Using yeast display protein variants, identified 25 residues to be critical for recognition neutralizing MAbs. These cluster into six novel one previously characterized located ridge DI, linker region between DI DIII, hinge interface DII, ridge, central interface, dimer fusion loop DII. Approximately 45% DI-DII-specific showed reduced binding with mutations highly conserved DII: 85% these (34 40) cross-reacted distantly related dengue (DENV). In contrast, bound other epitopes DII no apparent cross-reactivity DENV Surprisingly, several were solvent-inaccessible positions context available pseudoatomic model WNV. Nonetheless, mice, albeit lower efficiency than DIII-specific