This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Guillaume, V. Articles by Langedijk, J. P. M. Search for Related Content PubMed PubMed Citation Articles by Guillaume, V. Articles by Langedijk, J. P. M.

 Previous Article  |  Next Article 

Journal of Virology, August 2006, p. 7546-7554, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.00190-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Evidence of a Potential Receptor-Binding Site on the Nipah Virus G Protein (NiV-G): Identification of Globular Head Residues with a Role in Fusion Promotion and Their Localization on an NiV-G Structural Model

Vanessa Guillaume,^1, Hamide Aslan,^1, Michelle Ainouze,¹ Mathilde Guerbois,¹ T. Fabian Wild,² Robin Buckland,^1* and Johannes P. M. Langedijk³

Molecular Basis of Paramyxovirus Entry,¹ Immunobiology of Viral Infections, INSERM U404, Immunité et Vaccination, Centre d’Etudes de Recherche en Virologie et Immunologie, IFR 128 Biosciences Lyon-Gerland, Université Claude Bernard, Lyon, France,² Pepscan Systems Inc., Lelystad, The Netherlands³

Received 27 January 2006/ Accepted 15 May 2006

As a preliminary to the localization of the receptor-binding site(s) on the Nipah virus (NiV) glycoprotein (NiV-G), we have undertaken the identification of NiV-G residues that play a role in fusion promotion. To achieve this, we have used two strategies. First, as NiV and Hendra virus (HeV) share a common receptor and their cellular tropism is similar, we hypothesized that residues functioning in receptor attachment could be conserved between their respective G proteins. Our initial strategy was to target charged residues (which can be expected to be at the surface of the protein) conserved between the NiV-G and HeV-G globular heads. Second, we generated NiV variants that escaped neutralization by anti-NiV-G monoclonal antibodies (MAbs) that neutralize NiV both in vitro and in vivo, likely by blocking receptor attachment. The sequencing of such "escape mutants" identified NiV-G residues present in the epitopes to which the neutralizing MAbs are directed. Residues identified via these two strategies whose mutation had an effect on fusion promotion were localized on a new structural model for the NiV-G protein. Our results suggest that seven NiV-G residues, including one (E533) that was identified using both strategies, form a contiguous site on the top of the globular head that is implicated in ephrinB2 binding. This site commences near the shallow depression in the center of the top surface of the globular head and extends to the rim of the barrel-like structure on the top loops of ß-sheet 5. The topology of this site is strikingly similar to that proposed to form the SLAM receptor site on another paramyxovirus attachment protein, that of the measles virus hemagglutinin.

These authors contributed equally to this study.

This article has been cited by other articles:

• Negrete, O. A., Chu, D., Aguilar, H. C., Lee, B. (2007). Single Amino Acid Changes in the Nipah and Hendra Virus Attachment Glycoproteins Distinguish EphrinB2 from EphrinB3 Usage. J. Virol. 81: 10804-10814 [Abstract] [Full Text]  
• Bishop, K. A., Stantchev, T. S., Hickey, A. C., Khetawat, D., Bossart, K. N., Krasnoperov, V., Gill, P., Feng, Y. R., Wang, L., Eaton, B. T., Wang, L.-F., Broder, C. C. (2007). Identification of Hendra Virus G Glycoprotein Residues That Are Critical for Receptor Binding. J. Virol. 81: 5893-5901 [Abstract] [Full Text]