Journal article
N-Glycans on Nipah Virus Fusion Protein Protect against Neutralization but Reduce Membrane Fusion and Viral Entry
Journal of virology, Vol.80(10), pp.4878-4889
05/2006
Handle:
https://hdl.handle.net/2376/117400
PMCID: PMC1472062
PMID: 16641279
Abstract
Nipah virus (NiV) is a deadly emerging paramyxovirus. The NiV attachment (NiV-G) and fusion (NiV-F) envelope glycoproteins mediate both syncytium formation and viral entry. Specific N-glycans on paramyxovirus fusion proteins are generally required for proper conformational integrity and biological function. However, removal of individual N-glycans on NiV-F had little negative effect on processing or fusogenicity and has even resulted in slightly increased fusogenicity. Here, we report that in both syncytium formation and viral entry assays, removal of multiple N-glycans on NiV-F resulted in marked increases in fusogenicity (>5-fold) but also resulted in increased sensitivity to neutralization by NiV-F-specific antisera. The mechanism underlying the hyperfusogenicity of these NiV-F N-glycan mutants is likely due to more-robust six-helix bundle formation, as these mutants showed increased fusion kinetics and were more resistant to neutralization by a fusion-inhibitory reagent based on the C-terminal heptad repeat region of NiV-F. Finally, we demonstrate that the fusogenicities of the NiV-F N-glycan mutants were inversely correlated with the relative avidities of NiV-F's interactions with NiV-G, providing support for the attachment protein “displacement” model of paramyxovirus fusion. Our results indicate that N-glycans on NiV-F protect NiV from antibody neutralization, suggest that this “shielding” role comes together with limiting cell-cell fusion and viral entry efficiencies, and point to the mechanisms underlying the hyperfusogenicity of these N-glycan mutants. These features underscore the varied roles that N-glycans on NiV-F play in the pathobiology of NiV entry but also shed light on the general mechanisms of paramyxovirus fusion with host cells.
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Details
- Title
- N-Glycans on Nipah Virus Fusion Protein Protect against Neutralization but Reduce Membrane Fusion and Viral Entry
- Creators
- Hector C Aguilar - Department of Microbiology, Immunology and Molecular GeneticsKenneth A Matreyek - Department of Microbiology, Immunology and Molecular GeneticsClaire Marie Filone - Department of Microbiology, Immunology and Molecular GeneticsSara T Hashimi - Department of Microbiology, Immunology and Molecular GeneticsErnest L Levroney - Department of Microbiology, Immunology and Molecular GeneticsOscar A Negrete - Department of Microbiology, Immunology and Molecular GeneticsAndrea Bertolotti-Ciarlet - Department of Microbiology, Immunology and Molecular GeneticsDaniel Y Choi - Department of Microbiology, Immunology and Molecular GeneticsIan McHardy - Department of Microbiology, Immunology and Molecular GeneticsJennifer A Fulcher - Department of Microbiology, Immunology and Molecular GeneticsStephen V Su - Department of Microbiology, Immunology and Molecular GeneticsMike C Wolf - Department of Microbiology, Immunology and Molecular GeneticsLuciana Kohatsu - Department of Microbiology, Immunology and Molecular GeneticsLinda G Baum - Department of Microbiology, Immunology and Molecular GeneticsBenhur Lee - Department of Microbiology, Immunology and Molecular Genetics
- Publication Details
- Journal of virology, Vol.80(10), pp.4878-4889
- Academic Unit
- Paul G. Allen School for Global Animal Health
- Publisher
- American Society for Microbiology
- Identifiers
- 99900548580601842
- Language
- English
- Resource Type
- Journal article