The molecular basis of antigenic variation among A(H9N2) avian influenza viruses

Peacock, T. P., Harvey, W. T., Sadeyen, J.-R., Reeve, R. and Iqbal, M. (2018) The molecular basis of antigenic variation among A(H9N2) avian influenza viruses. Emerging Microbes and Infections, 7, 176. (doi: 10.1038/s41426-018-0178-y) (PMID:30401826) (PMCID:PMC6220119)

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Avian influenza A(H9N2) viruses are an increasing threat to global poultry production and, through zoonotic infection, to human health where they are considered viruses with pandemic potential. Vaccination of poultry is a key element of disease control in endemic countries, but vaccine effectiveness is persistently challenged by the emergence of antigenic variants. Here we employed a combination of techniques to investigate the genetic basis of H9N2 antigenic variability and evaluate the role of different molecular mechanisms of immune escape. We systematically tested the influence of published H9N2 monoclonal antibody escape mutants on chicken antisera binding, determining that many have no significant effect. Substitutions introducing additional glycosylation sites were a notable exception, though these are relatively rare among circulating viruses. To identify substitutions responsible for antigenic variation in circulating viruses, we performed an integrated meta-analysis of all published H9 haemagglutinin sequences and antigenic data. We validated this statistical analysis experimentally and allocated several new residues to H9N2 antigenic sites, providing molecular markers that will help explain vaccine breakdown in the field and inform vaccine selection decisions. We find evidence for the importance of alternative mechanisms of immune escape, beyond simple modulation of epitope structure, with substitutions increasing glycosylation or receptor-binding avidity, exhibiting the largest impacts on chicken antisera binding. Of these, meta-analysis indicates avidity regulation to be more relevant to the evolution of circulating viruses, suggesting that a specific focus on avidity regulation is required to fully understand the molecular basis of immune escape by influenza, and potentially other viruses.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Reeve, Dr Richard and Harvey, Dr William
Authors: Peacock, T. P., Harvey, W. T., Sadeyen, J.-R., Reeve, R., and Iqbal, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:Emerging Microbes and Infections
Publisher:Springer Nature
ISSN (Online):2222-1751
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Emerging Microbes and Infections 7: 176
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
580944MRC Doctoral Training Grant 2011-2015Mary Beth KneafseyMedical Research Council (MRC)MR/J50032X/1 (AFS3)VPO VICE PRINCIPAL RESEARCH & ENTERPRISE
3026320Using a comparative One Health approach to investigate the structural basis of antigenic variation among human and avian influenza virusesJill PellMedical Research Council (MRC)MR/R024758/1Institute of Biodiversity, Animal Health and Comparative Medicine
632421An effective vaccination programme for the eradication of foot-and-mouth disease from IndiaRichard ReeveBiotechnology and Biological Sciences Research Council (BBSRC)BB/L004828/1 1805RI BIODIVERSITY ANIMAL HEALTH & COMPMED
730011Mathematical Theory and Biological Applications of DiversityRichard ReeveBiotechnology and Biological Sciences Research Council (BBSRC)BB/P004202/1RI BIODIVERSITY ANIMAL HEALTH & COMPMED