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Crystal structure and carbohydrate analysis of Nipah virus attachment glycoprotein: a template for antiviral and vaccine design

Crystal structure and carbohydrate analysis of Nipah virus attachment glycoprotein: a template for antiviral and vaccine design
Crystal structure and carbohydrate analysis of Nipah virus attachment glycoprotein: a template for antiviral and vaccine design

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-Å 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.

0022-538X
11628-11636
Bowden, Thomas A.
4b17a588-ac01-4112-807a-8b99a6c20d0f
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Harvey, David J.
8bb24417-3852-4b1f-827b-0d5d2c176744
Aricescu, A. Radu
8ee3d2bd-7ef7-4e85-862a-e13f48ae0fa6
Grimes, Jonathan M.
f6822086-e726-4829-8c75-823e581bcb76
Jones, E. Yvonne
6b9004c9-137b-4f43-8a14-c7c83bcaa4be
Stuart, David I.
2751c230-9d4c-4981-aeb7-cafb51ed749d
Bowden, Thomas A.
4b17a588-ac01-4112-807a-8b99a6c20d0f
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Harvey, David J.
8bb24417-3852-4b1f-827b-0d5d2c176744
Aricescu, A. Radu
8ee3d2bd-7ef7-4e85-862a-e13f48ae0fa6
Grimes, Jonathan M.
f6822086-e726-4829-8c75-823e581bcb76
Jones, E. Yvonne
6b9004c9-137b-4f43-8a14-c7c83bcaa4be
Stuart, David I.
2751c230-9d4c-4981-aeb7-cafb51ed749d

Bowden, Thomas A., Crispin, Max, Harvey, David J., Aricescu, A. Radu, Grimes, Jonathan M., Jones, E. Yvonne and Stuart, David I. (2008) Crystal structure and carbohydrate analysis of Nipah virus attachment glycoprotein: a template for antiviral and vaccine design. Journal of Virology, 82 (23), 11628-11636. (doi:10.1128/JVI.01344-08).

Record type: Article

Abstract

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-Å 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.

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Published date: December 2008

Identifiers

Local EPrints ID: 414584
URI: https://eprints.soton.ac.uk/id/eprint/414584
ISSN: 0022-538X
PURE UUID: f207e7e9-6fba-44ec-a56c-6731cb5cd169
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

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Date deposited: 04 Oct 2017 16:30
Last modified: 12 Nov 2019 01:27

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