Document Detail


Crystal structure and carbohydrate analysis of Nipah virus attachment glycoprotein: a template for antiviral and vaccine design.
MedLine Citation:
PMID:  18815311     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Two members of the paramyxovirus family, Nipah virus (NiV) and Hendra virus (HeV), are recent additions to a growing number of agents of emergent diseases which use bats as a natural host. Identification of ephrin-B2 and ephrin-B3 as cellular receptors for these viruses has enabled the development of immunotherapeutic reagents which prevent virus attachment and subsequent fusion. Here we present the structural analysis of the protein and carbohydrate components of the unbound viral attachment glycoprotein of NiV glycoprotein (NiV-G) at a 2.2-A resolution. Comparison with its ephrin-B2-bound form reveals that conformational changes within the envelope glycoprotein are required to achieve viral attachment. Structural differences are particularly pronounced in the 579-590 loop, a major component of the ephrin binding surface. In addition, the 236-245 loop is rather disordered in the unbound structure. We extend our structural characterization of NiV-G with mass spectrometric analysis of the carbohydrate moieties. We demonstrate that NiV-G is largely devoid of the oligomannose-type glycans that in viruses such as human immunodeficiency virus type 1 and Ebola virus influence viral tropism and the host immune response. Nevertheless, we find putative ligands for the endothelial cell lectin, LSECtin. Finally, by mapping structural conservation and glycosylation site positions from other members of the paramyxovirus family, we suggest the molecular surface involved in oligomerization. These results suggest possible pathways of virus-host interaction and strategies for the optimization of recombinant vaccines.
Authors:
Thomas A Bowden; Max Crispin; David J Harvey; A Radu Aricescu; Jonathan M Grimes; E Yvonne Jones; David I Stuart
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-09-24
Journal Detail:
Title:  Journal of virology     Volume:  82     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-12     Completed Date:  2008-11-25     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11628-36     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Antiviral Agents / pharmacology*
Carbohydrates / chemistry*
Cells, Cultured
Crystallization
Drug Design
Glycosylation
Humans
Nipah Virus / chemistry*,  drug effects,  immunology
Protein Conformation
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Vaccines, Synthetic / immunology*
Viral Envelope Proteins / chemistry*
Viral Vaccines / immunology*
Grant Support
ID/Acronym/Agency:
G0500365//Medical Research Council; G0700232//Medical Research Council; //Cancer Research UK; //Medical Research Council; //Wellcome Trust
Chemical
Reg. No./Substance:
0/Antiviral Agents; 0/Carbohydrates; 0/Vaccines, Synthetic; 0/Viral Envelope Proteins; 0/Viral Vaccines; 0/attachment protein G
Comments/Corrections

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