Individual N-Glycans Added at Intervals along the Stalk of the Nipah Virus G Protein Prevent Fusion but Do Not Block the Interaction with the Homologous F Protein

Qiyun Zhu; Scott B Biering; Anne M Mirza; Brittany A Grasseschi; Paul J Mahon; Benhur Lee; Hector C Aguilar; Ronald M Iorio

doi:10.1128/JVI.03084-12

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Individual N-Glycans Added at Intervals along the Stalk of the Nipah Virus G Protein Prevent Fusion but Do Not Block the Interaction with the Homologous F Protein

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Individual N-Glycans Added at Intervals along the Stalk of the Nipah Virus G Protein Prevent Fusion but Do Not Block the Interaction with the Homologous F Protein

Qiyun Zhu, Scott B Biering, Anne M Mirza, Brittany A Grasseschi, Paul J Mahon, Benhur Lee, Hector C Aguilar and Ronald M Iorio

Journal of virology, Vol.87(6), pp.3119-3129

03/2013

DOI: https://doi.org/10.1128/JVI.03084-12

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https://hdl.handle.net/2376/110635

PMCID: PMC3592174

PMID: 23283956

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Abstract

Virus-Cell Interactions

The promotion of membrane fusion by most paramyxoviruses requires an interaction between the viral attachment and fusion (F) proteins to enable receptor binding by the former to trigger the activation of the latter for fusion. Numerous studies demonstrate that the F-interactive sites on the Newcastle disease virus (NDV) hemagglutinin-neuraminidase (HN) and measles virus (MV) hemagglutinin (H) proteins reside entirely within the stalk regions of those proteins. Indeed, stalk residues of NDV HN and MV H that likely mediate the F interaction have been identified. However, despite extensive efforts, the F-interactive site(s) on the Nipah virus (NiV) G attachment glycoprotein has not been identified. In this study, we have introduced individual N-linked glycosylation sites at several positions spaced at intervals along the stalk of the NiV G protein. Five of the seven introduced sites are utilized as established by a retardation of electrophoretic mobility. Despite surface expression, ephrinB2 binding, and oligomerization comparable to those of the wild-type protein, four of the five added N-glycans completely eliminate the ability of the G protein to complement the homologous F protein in the promotion of fusion. The most membrane-proximal added N-glycan reduces fusion by 80%. However, unlike similar NDV HN and MV H mutants, the NiV G glycosylation stalk mutants retain the ability to bind F, indicating that the fusion deficiency of these mutants is not due to prevention of the G-F interaction. These findings suggest that the G-F interaction is not mediated entirely by the stalk domain of G and may be more complex than that of HN/H-F.

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Title: Individual N-Glycans Added at Intervals along the Stalk of the Nipah Virus G Protein Prevent Fusion but Do Not Block the Interaction with the Homologous F Protein
Creators: Qiyun Zhu - Department of Microbiology and Physiological Systems
Scott B Biering - Paul G. Allen School for Global Animal Health
Anne M Mirza - Department of Microbiology and Physiological Systems
Brittany A Grasseschi - Department of Microbiology and Physiological Systems
Paul J Mahon - Department of Microbiology and Physiological Systems
Benhur Lee - Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at University of California—Los Angeles, Los Angeles, California, USA
Hector C Aguilar - Paul G. Allen School for Global Animal Health
Ronald M Iorio - Department of Microbiology and Physiological Systems
Publication Details: Journal of virology, Vol.87(6), pp.3119-3129
Academic Unit: Paul G. Allen School for Global Animal Health
Publisher: American Society for Microbiology; 1752 N St., N.W., Washington, DC
Identifiers: 99900546910901842
Language: English
Resource Type: Journal article