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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.



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