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Crystal structure and carbohydrate analysis of Nipah virus attachment glycoprotein: a template for antiviral and vaccine design

DOI: 10.1128/JVI.01344-08 DOI Help
PMID: 18815311 PMID Help

Authors: Thomas Bowden (Division of Structural Biology, University of Oxford) , Max Crispin (Division of Structural Biology, University of Oxford) , D. J. Harvey (Division of Structural Biology, University of Oxford) , Alexandru Aricescu (Division of Structural Biology, University of Oxford) , Jonathan Grimes (Division of Structural Biology, University of Oxford) , E. Y. Jones (Division of Structural Biology, University of Oxford) , Dave Stuart (Division of Structural Biology, University of Oxford, Diamond Light Source)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Virology , VOL 82 (23) , PAGES 11628-36

State: Published (Approved)
Published: November 2008

Abstract: Two members of the paramyxovirus family, Nipah virus (NiV) and Hendra virus (HeV), are recent additions to a growing number of agents of emergent diseases which use bats as a natural host. Identification of ephrin-B2 and ephrin-B3 as cellular receptors for these viruses has enabled the development of immunotherapeutic reagents which prevent virus attachment and subsequent fusion. Here we present the structural analysis of the protein and carbohydrate components of the unbound viral attachment glycoprotein of NiV glycoprotein (NiV-G) at a 2.2-Å resolution. Comparison with its ephrin-B2-bound form reveals that conformational changes within the envelope glycoprotein are required to achieve viral attachment. Structural differences are particularly pronounced in the 579-590 loop, a major component of the ephrin binding surface. In addition, the 236-245 loop is rather disordered in the unbound structure. We extend our structural characterization of NiV-G with mass spectrometric analysis of the carbohydrate moieties. We demonstrate that NiV-G is largely devoid of the oligomannose-type glycans that in viruses such as human immunodeficiency virus type 1 and Ebola virus influence viral tropism and the host immune response. Nevertheless, we find putative ligands for the endothelial cell lectin, LSECtin. Finally, by mapping structural conservation and glycosylation site positions from other members of the paramyxovirus family, we suggest the molecular surface involved in oligomerization. These results suggest possible pathways of virus-host interaction and strategies for the optimization of recombinant vaccines.

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography

Added On: 03/04/2009 11:35

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