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Molecules 2015, 20(6), 10415-10434; doi:10.3390/molecules200610415

Molecular Characterisation of the Haemagglutinin Glycan-Binding Specificity of Egg-Adapted Vaccine Strains of the Pandemic 2009 H1N1 Swine Influenza A Virus

1
AgResearch Limited, Grasslands Research Centre, Tennent Drive, Private Bag 11008, Palmerston North 4442, New Zealand
2
Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville 3052, Victoria, Australia
3
CSL Limited Poplar Road, Parkville 3052, Victoria, Australia
4
Priority Research Centre in Reproductive Science, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia
5
Institute for Molecular Bioscience, University of Queensland, 306 Carmody Road St Lucia, QLD 4072, Brisbane, Australia
*
Author to whom correspondence should be addressed.
Academic Editors: Els Van Damme and Kristof De Schutter
Received: 13 May 2015 / Accepted: 1 June 2015 / Published: 5 June 2015
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
View Full-Text   |   Download PDF [3553 KB, uploaded 5 June 2015]   |  

Abstract

The haemagglutinin (HA) glycan binding selectivity of H1N1 influenza viruses is an important determinant for the host range of the virus and egg-adaption during vaccine production. This study integrates glycan binding data with structure-recognition models to examine the impact of the K123N, D225G and Q226R mutations (as seen in the HA of vaccine strains of the pandemic 2009 H1N1 swine influenza A virus). The glycan-binding selectivity of three A/California/07/09 vaccine production strains, and purified recombinant A/California/07/09 HAs harboring these mutations was examined via a solid-phase ELISA assay. Wild-type A/California/07/09 recombinant HA bound specifically to α2,6-linked sialyl-glycans, with no affinity for the α2,3-linked sialyl-glycans in the array. In contrast, the vaccine virus strains and recombinant HA harboring the Q226R HA mutation displayed a comparable pattern of highly specific binding to α2,3-linked sialyl-glycans, with a negligible affinity for α2,6-linked sialyl-glycans. The D225G A/California/07/09 recombinant HA displayed an enhanced binding affinity for both α2,6- and α2,3-linked sialyl-glycans in the array. Notably its α2,6-glycan affinity was generally higher compared to its α2,3-glycan affinity, which may explain why the double mutant was not naturally selected during egg-adaption of the virus. The K123N mutation which introduces a glycosylation site proximal to the receptor binding site, did not impact the α2,3/α2,6 glycan selectivity, however, it lowered the overall glycan binding affinity of the HA; suggesting glycosylation may interfere with receptor binding. Docking models and ‘per residues’ scoring were employed to provide a structure-recognition rational for the experimental glycan binding data. Collectively, the glycan binding data inform future vaccine design strategies to introduce the D225G or Q226R amino acid substitutions into recombinant H1N1 viruses. View Full-Text
Keywords: pandemic H1N1 swine influenza A virus; haemagglutinin; glycan binding specificity; egg-adaption pandemic H1N1 swine influenza A virus; haemagglutinin; glycan binding specificity; egg-adaption
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Carbone, V.; Schneider, E.K.; Rockman, S.; Baker, M.; Huang, J.X.; Ong, C.; Cooper, M.A.; Yuriev, E.; Li, J.; Velkov, T. Molecular Characterisation of the Haemagglutinin Glycan-Binding Specificity of Egg-Adapted Vaccine Strains of the Pandemic 2009 H1N1 Swine Influenza A Virus. Molecules 2015, 20, 10415-10434.

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