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Journal of Virology, December 2008, p. 11628-11636, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.01344-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Crystal Structure and Carbohydrate Analysis of Nipah Virus Attachment Glycoprotein: a Template for Antiviral and Vaccine Design{triangledown} ,{dagger}

Thomas A. Bowden,1 Max Crispin,1 David J. Harvey,2 A. Radu Aricescu,1 Jonathan M. Grimes,1 E. Yvonne Jones,1 and David I. Stuart1*

Division of Structural Biology, University of Oxford, Henry Wellcome Building of Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, United Kingdom,1 Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom2

Received 26 June 2008/ Accepted 5 September 2008

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.

* Corresponding author. Mailing address: Division of Structural Biology, University of Oxford, Henry Wellcome Building of Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, United Kingdom. Phone: 441865 287546. Fax: 441865 287547. E-mail: dave{at}strubi.ox.ac.uk

{triangledown} Published ahead of print on 24 September 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, December 2008, p. 11628-11636, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.01344-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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