Document Detail


N-Glycans on the Nipah virus attachment glycoprotein modulate fusion and viral entry as they protect against antibody neutralization.
MedLine Citation:
PMID:  22915812     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Scott B Biering; Andrew Huang; Andy T Vu; Lindsey R Robinson; Birgit Bradel-Tretheway; Eric Choi; Benhur Lee; Hector C Aguilar
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-08-22
Journal Detail:
Title:  Journal of virology     Volume:  86     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-22     Completed Date:  2013-01-11     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11991-2002     Citation Subset:  IM    
Affiliation:
Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
CHO Cells
Cell Membrane / virology
Cricetinae
Ephrin-B2 / metabolism
Ephrin-B3 / metabolism
Glycoproteins / chemistry*
Glycosylation
HEK293 Cells
Humans
Membrane Fusion / genetics
Molecular Conformation
Mutation
Nipah Virus / metabolism*
Phenotype
Polysaccharides / chemistry*
Protein Binding
Viral Fusion Proteins / chemistry
Virus Attachment*
Grant Support
ID/Acronym/Agency:
AI069317/AI/NIAID NIH HHS; AI094329/AI/NIAID NIH HHS; R21 AI094329/AI/NIAID NIH HHS; U54 AI065359/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Ephrin-B2; 0/Ephrin-B3; 0/Glycoproteins; 0/Polysaccharides; 0/Viral Fusion Proteins
Comments/Corrections

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