This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kanai, R.
Right arrow Articles by Modis, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kanai, R.
Right arrow Articles by Modis, Y.

 Previous Article  |  Next Article 

Journal of Virology, November 2006, p. 11000-11008, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.01735-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Crystal Structure of West Nile Virus Envelope Glycoprotein Reveals Viral Surface Epitopes{triangledown}

Ryuta Kanai,1 Kalipada Kar,2 Karen Anthony,2 L. Hannah Gould,3,{dagger} Michel Ledizet,2 Erol Fikrig,3 Wayne A. Marasco,4 Raymond A. Koski,2 and Yorgo Modis1*

Department of Molecular Biophysics and Biochemistry, The Bass Center for Structural Biology, Yale University, 266 Whitney Ave., New Haven, Connecticut 06520,1 L Diagnostics, 300 George St., New Haven, Connecticut 06511,2 Department of Epidemiology and Public Health and Department of Internal Medicine, Yale School of Medicine, 300 Cedar St., New Haven, Connecticut 06520,3 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney St., Boston, Massachusetts 021154

Received 10 August 2006/ Accepted 25 August 2006

West Nile virus, a member of the Flavivirus genus, causes fever that can progress to life-threatening encephalitis. The major envelope glycoprotein, E, of these viruses mediates viral attachment and entry by membrane fusion. We have determined the crystal structure of a soluble fragment of West Nile virus E. The structure adopts the same overall fold as that of the E proteins from dengue and tick-borne encephalitis viruses. The conformation of domain II is different from that in other prefusion E structures, however, and resembles the conformation of domain II in postfusion E structures. The epitopes of neutralizing West Nile virus-specific antibodies map to a region of domain III that is exposed on the viral surface and has been implicated in receptor binding. In contrast, we show that certain recombinant therapeutic antibodies, which cross-neutralize West Nile and dengue viruses, bind a peptide from domain I that is exposed only during the membrane fusion transition. By revealing the details of the molecular landscape of the West Nile virus surface, our structure will assist the design of antiviral vaccines and therapeutics.

* Corresponding author. Mailing address: 266 Whitney Ave., Bass 430, New Haven, CT 06520. Phone: (203) 432-4330. Fax: (203) 432-1296. E-mail: yorgo.modis{at}yale.edu.

{triangledown} Published ahead of print on 30 August 2006.

{dagger} Present address: Bacterial Diseases Branch, Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80522.

Journal of Virology, November 2006, p. 11000-11008, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.01735-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Yu, I.-M., Holdaway, H. A., Chipman, P. R., Kuhn, R. J., Rossmann, M. G., Chen, J. (2009). Association of the pr Peptides with Dengue Virus at Acidic pH Blocks Membrane Fusion. J. Virol. 83: 12101-12107 [Abstract] [Full Text]  
  • Nelson, S., Poddar, S., Lin, T.-Y., Pierson, T. C. (2009). Protonation of Individual Histidine Residues Is Not Required for the pH-Dependent Entry of West Nile Virus: Evaluation of the "Histidine Switch" Hypothesis. J. Virol. 83: 12631-12635 [Abstract] [Full Text]  
  • Kiermayr, S., Stiasny, K., Heinz, F. X. (2009). Impact of Quaternary Organization on the Antigenic Structure of the Tick-Borne Encephalitis Virus Envelope Glycoprotein E. J. Virol. 83: 8482-8491 [Abstract] [Full Text]  
  • Vogt, M. R., Moesker, B., Goudsmit, J., Jongeneelen, M., Austin, S. K., Oliphant, T., Nelson, S., Pierson, T. C., Wilschut, J., Throsby, M., Diamond, M. S. (2009). Human Monoclonal Antibodies against West Nile Virus Induced by Natural Infection Neutralize at a Postattachment Step. J. Virol. 83: 6494-6507 [Abstract] [Full Text]  
  • Sultana, H., Foellmer, H. G., Neelakanta, G., Oliphant, T., Engle, M., Ledizet, M., Krishnan, M. N., Bonafe, N., Anthony, K. G., Marasco, W. A., Kaplan, P., Montgomery, R. R., Diamond, M. S., Koski, R. A., Fikrig, E. (2009). Fusion Loop Peptide of the West Nile Virus Envelope Protein Is Essential for Pathogenesis and Is Recognized by a Therapeutic Cross-Reactive Human Monoclonal Antibody. J. Immunol. 183: 650-660 [Abstract] [Full Text]  
  • Wang, Q.-Y., Patel, S. J., Vangrevelinghe, E., Xu, H. Y., Rao, R., Jaber, D., Schul, W., Gu, F., Heudi, O., Ma, N. L., Poh, M. K., Phong, W. Y., Keller, T. H., Jacoby, E., Vasudevan, S. G. (2009). A Small-Molecule Dengue Virus Entry Inhibitor. Antimicrob. Agents Chemother. 53: 1823-1831 [Abstract] [Full Text]  
  • Nayak, V., Dessau, M., Kucera, K., Anthony, K., Ledizet, M., Modis, Y. (2009). Crystal Structure of Dengue Virus Type 1 Envelope Protein in the Postfusion Conformation and Its Implications for Membrane Fusion. J. Virol. 83: 4338-4344 [Abstract] [Full Text]  
  • Rajamanonmani, R., Nkenfou, C., Clancy, P., Yau, Y. H., Shochat, S. G., Sukupolvi-Petty, S., Schul, W., Diamond, M. S., Vasudevan, S. G., Lescar, J. (2009). On a mouse monoclonal antibody that neutralizes all four dengue virus serotypes. J. Gen. Virol. 90: 799-809 [Abstract] [Full Text]  
  • Fritz, R., Stiasny, K., Heinz, F. X. (2008). Identification of specific histidines as pH sensors in flavivirus membrane fusion. JCB 183: 353-361 [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]  
  • 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]  
  • Li, L., Lok, S.-M., Yu, I-M., Zhang, Y., Kuhn, R. J., Chen, J., Rossmann, M. G. (2008). The Flavivirus Precursor Membrane-Envelope Protein Complex: Structure and Maturation. Science 319: 1830-1834 [Abstract] [Full Text]  
  • Yu, I-M., Zhang, W., Holdaway, H. A., Li, L., Kostyuchenko, V. A., Chipman, P. R., Kuhn, R. J., Rossmann, M. G., Chen, J. (2008). Structure of the Immature Dengue Virus at Low pH Primes Proteolytic Maturation. Science 319: 1834-1837 [Abstract] [Full Text]  
  • Falconar, A. K. I. (2008). Monoclonal Antibodies That Bind to Common Epitopes on the Dengue Virus Type 2 Nonstructural-1 and Envelope Glycoproteins Display Weak Neutralizing Activity and Differentiated Responses to Virulent Strains: Implications for Pathogenesis and Vaccines. CVI 15: 549-561 [Abstract] [Full Text]  
  • Arjona, A., Ledizet, M., Anthony, K., Bonafe, N., Modis, Y., Town, T., Fikrig, E. (2007). West Nile Virus Envelope Protein Inhibits dsRNA-Induced Innate Immune Responses. J. Immunol. 179: 8403-8409 [Abstract] [Full Text]  
  • Stiasny, K., Brandler, S., Kossl, C., Heinz, F. X. (2007). Probing the Flavivirus Membrane Fusion Mechanism by Using Monoclonal Antibodies. J. Virol. 81: 11526-11531 [Abstract] [Full Text]  
  • Lisova, O., Hardy, F., Petit, V., Bedouelle, H. (2007). Mapping to completeness and transplantation of a group-specific, discontinuous, neutralizing epitope in the envelope protein of dengue virus. J. Gen. Virol. 88: 2387-2397 [Abstract] [Full Text]  
  • Zhang, Y., Kaufmann, B., Chipman, P. R., Kuhn, R. J., Rossmann, M. G. (2007). Structure of Immature West Nile Virus. J. Virol. 81: 6141-6145 [Abstract] [Full Text]  
  • Schlesinger, J. J. (2006). Flavivirus nonstructural protein NS1: Complementary surprises. Proc. Natl. Acad. Sci. USA 103: 18879-18880 [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»