N-Glycans on the Nipah virus attachment glycoprotein modulate fusion and viral entry as they protect against antibody neutralization

Scott B Biering; Andrew Huang; Andy T Vu; Lindsey R Robinson; Birgit Bradel-Tretheway; Eric Choi; Benhur Lee; Hector C Aguilar

doi:10.1128/JVI.01304-12

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N-Glycans on the Nipah virus attachment glycoprotein modulate fusion and viral entry as they protect against antibody neutralization

Journal article

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N-Glycans on the Nipah virus attachment glycoprotein modulate fusion and viral entry as they protect against antibody neutralization

Scott B Biering, Andrew Huang, Andy T Vu, Lindsey R Robinson, Birgit Bradel-Tretheway, Eric Choi, Benhur Lee and Hector C Aguilar

Journal of virology, Vol.86(22), pp.11991-12002

11/2012

DOI: https://doi.org/10.1128/JVI.01304-12

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https://hdl.handle.net/2376/100413

PMCID: PMC3486489

PMID: 22915812

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Abstract

Cricetinae

Humans

Molecular Conformation

Nipah Virus - metabolism

Membrane Fusion - genetics

Ephrin-B3 - metabolism

Glycosylation

Ephrin-B2 - metabolism

Animals

Viral Fusion Proteins - chemistry

HEK293 Cells

Virus Attachment

Polysaccharides - chemistry

Protein Binding

Cell Membrane - virology

Glycoproteins - chemistry

CHO Cells

Phenotype

Mutation

Nipah virus (NiV) is the deadliest known paramyxovirus. Membrane fusion is essential for NiV entry into host cells and for the virus' pathological induction of cell-cell fusion (syncytia). The mechanism by which the attachment glycoprotein (G), upon binding to the cell receptors ephrinB2 or ephrinB3, triggers the fusion glycoprotein (F) to execute membrane fusion is largely unknown. N-glycans on paramyxovirus glycoproteins are generally required for proper protein conformational integrity, transport, and sometimes biological functions. We made conservative mutations (Asn to Gln) at the seven potential N-glycosylation sites in the NiV G ectodomain (G1 to G7) individually or in combination. Six of the seven N-glycosylation sites were found to be glycosylated. Moreover, pseudotyped virions carrying these N-glycan mutants had increased antibody neutralization sensitivities. Interestingly, our results revealed hyperfusogenic and hypofusogenic phenotypes for mutants that bound ephrinB2 at wild-type levels, and the mutant's cell-cell fusion phenotypes generally correlated to viral entry levels. In addition, when removing multiple N-glycans simultaneously, we observed synergistic or dominant-negative membrane fusion phenotypes. Interestingly, our data indicated that 4- to 6-fold increases in fusogenicity resulted from multiple mechanisms, including but not restricted to the increase of F triggering. Altogether, our results suggest that NiV-G N-glycans play a role in shielding virions against antibody neutralization, while modulating cell-cell fusion and viral entry via multiple mechanisms.

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Title: N-Glycans on the Nipah virus attachment glycoprotein modulate fusion and viral entry as they protect against antibody neutralization
Creators: Scott B Biering - Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, USA
Andrew Huang
Andy T Vu
Lindsey R Robinson
Birgit Bradel-Tretheway
Eric Choi
Benhur Lee
Hector C Aguilar
Publication Details: Journal of virology, Vol.86(22), pp.11991-12002
Academic Unit: Elson S. Floyd College of Medicine
Publisher: United States
Grant note: R01 AI069317 / NIAID NIH HHS U54 AI065359 / NIAID NIH HHS AI094329 / NIAID NIH HHS R21 AI094329 / NIAID NIH HHS AI069317 / NIAID NIH HHS
Identifiers: 99900546568401842
Language: English
Resource Type: Journal article