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Title: Crystal Structure of West Nile Virus Envelope Glycoprotein Reveals Viral Surface Epitopes

Abstract

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.

Authors:
; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
930203
Report Number(s):
BNL-80866-2008-JA
Journal ID: ISSN 0022-538X; JOVIAM; TRN: US200822%%1383
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Journal Name:
Journal of Virology
Additional Journal Information:
Journal Volume: 80; Journal ID: ISSN 0022-538X
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; ANTIBODIES; CRYSTAL STRUCTURE; DESIGN; ENCEPHALITIS; FEVER; GLYCOPROTEINS; MAPS; MEMBRANES; PEPTIDES; PROTEINS; RECEPTORS; SURFACES; VACCINES; VIRUSES; national synchrotron light source

Citation Formats

Kanai, R, Kar, K, Anthony, K, Gould, L, Ledizet, M, Fikrig, E, Marasco, W, Koski, R, and Modis, Y. Crystal Structure of West Nile Virus Envelope Glycoprotein Reveals Viral Surface Epitopes. United States: N. p., 2006. Web. doi:10.1128/JVI.01735-06.
Kanai, R, Kar, K, Anthony, K, Gould, L, Ledizet, M, Fikrig, E, Marasco, W, Koski, R, & Modis, Y. Crystal Structure of West Nile Virus Envelope Glycoprotein Reveals Viral Surface Epitopes. United States. https://doi.org/10.1128/JVI.01735-06
Kanai, R, Kar, K, Anthony, K, Gould, L, Ledizet, M, Fikrig, E, Marasco, W, Koski, R, and Modis, Y. 2006. "Crystal Structure of West Nile Virus Envelope Glycoprotein Reveals Viral Surface Epitopes". United States. https://doi.org/10.1128/JVI.01735-06.
@article{osti_930203,
title = {Crystal Structure of West Nile Virus Envelope Glycoprotein Reveals Viral Surface Epitopes},
author = {Kanai, R and Kar, K and Anthony, K and Gould, L and Ledizet, M and Fikrig, E and Marasco, W and Koski, R and Modis, Y},
abstractNote = {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.},
doi = {10.1128/JVI.01735-06},
url = {https://www.osti.gov/biblio/930203}, journal = {Journal of Virology},
issn = {0022-538X},
number = ,
volume = 80,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}