This Article Full Text (PDF) Other Versions of this Article: JVI.00432-07v1 81/23/12816    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sukupolvi-Petty, S. Articles by Diamond, M. S. Search for Related Content PubMed PubMed Citation Articles by Sukupolvi-Petty, S. Articles by Diamond, M. S.

 Previous Article  |  Next Article 

J. Virol. doi:10.1128/JVI.00432-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Type- and Sub-Complex-Specific Neutralizing Antibodies Against Domain III of Dengue Virus Type-2 Envelope Protein Recognize Adjacent Epitopes

Departments of Medicine, Pathology & Immunology, and Molecular Microbiology, Washington University School of Medicine, St Louis, MO Department of Medicine, University of Rochester, Rochester, NY. Centers for Disease Control and Prevention, Fort Collins, CO. Center for Biodefense and Emerging Infectious Diseases, Sealy Center for Vaccine Development, Institute for Human Infections and Immunity and Department of Pathology, University of Texas Medical Branch, Galveston, TX

^* To whom correspondence should be addressed. Email: diamond{at}borcim.wustl.edu.

	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 envelope (E) 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, sub-complex-specific, and cross-reactive mAbs that recognize DIII of the DENV type 2 (DENV-2) and have different neutralizing potential. 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, and was analogous in position to that observed with WNV-specific strongly neutralizing mAbs. Sub-complex-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 with poor neutralizing activity against DENV-2 that cross-reacted with all DENV serotypes and other flaviviruses recognize 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, sub-complex, and cross-reactive antibodies with different neutralizing potential.

This article has been cited by other articles:

• Gromowski, G. D., Barrett, N. D., Barrett, A. D. T. (2008). Characterization of Dengue Virus Complex-Specific Neutralizing Epitopes on Envelope Protein Domain III of Dengue 2 Virus. J. Virol. 82: 8828-8837 [Abstract] [Full Text]  
• Abd-Jamil, J., Cheah, C.-Y., AbuBakar, S. (2008). Dengue virus type 2 envelope protein displayed as recombinant phage attachment protein reveals potential cell binding sites. Protein Eng Des Sel 0: gzn041v1-7 [Abstract] [Full Text]  
• Goncalvez, A. P., Chien, C.-H., Tubthong, K., Gorshkova, I., Roll, C., Donau, O., Schuck, P., Yoksan, S., Wang, S.-D., Purcell, R. H., Lai, C.-J. (2008). Humanized Monoclonal Antibodies Derived from Chimpanzee Fabs Protect against Japanese Encephalitis Virus In Vitro and In Vivo. J. Virol. 82: 7009-7021 [Abstract] [Full Text]  
• Falconar, A. K. I. (2008). Use of synthetic peptides to represent surface-exposed epitopes defined by neutralizing dengue complex- and flavivirus group-reactive monoclonal antibodies on the native dengue type-2 virus envelope glycoprotein. J. Gen. Virol. 89: 1616-1621 [Abstract] [Full Text]  
• Lai, C.-Y., Tsai, W.-Y., Lin, S.-R., Kao, C.-L., Hu, H.-P., King, C.-C., Wu, H.-C., Chang, G.-J., Wang, W.-K. (2008). Antibodies to Envelope Glycoprotein of Dengue Virus during the Natural Course of Infection Are Predominantly Cross-Reactive and Recognize Epitopes Containing Highly Conserved Residues at the Fusion Loop of Domain II. J. Virol. 82: 6631-6643 [Abstract] [Full Text]  
• Chiou, S.-S., Crill, W. D., Chen, L.-K., Chang, G.-J. J. (2008). Enzyme-Linked Immunosorbent Assays Using Novel Japanese Encephalitis Virus Antigen Improve the Accuracy of Clinical Diagnosis of Flavivirus Infections. CVI 15: 825-835 [Abstract] [Full Text]