Characterization of A/H7 influenza virus global antigenic diversity and key determinants in the hemagglutinin globular head mediating A/H7N9 antigenic evolution

ABSTRACT Avian A/H7 influenza viruses are a global threat to animal and human health. These viruses continue to cause outbreaks in poultry and have caused the highest number of reported zoonotic infections to date, highlighting their pandemic threat. Evidence for antigenic diversification of avian A...

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Main Authors: Adinda Kok, Rachel Scheuer, Theo M. Bestebroer, David F. Burke, Samuel H. Wilks, Monique I. Spronken, Dennis de Meulder, Pascal Lexmond, Mark Pronk, Derek J. Smith, Sander Herfst, Ron A. M. Fouchier, Mathilde Richard
Format: Article
Language:English
Published: American Society for Microbiology 2023-10-01
Series:mBio
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Online Access:https://journals.asm.org/doi/10.1128/mbio.00488-23
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author Adinda Kok
Rachel Scheuer
Theo M. Bestebroer
David F. Burke
Samuel H. Wilks
Monique I. Spronken
Dennis de Meulder
Pascal Lexmond
Mark Pronk
Derek J. Smith
Sander Herfst
Ron A. M. Fouchier
Mathilde Richard
author_facet Adinda Kok
Rachel Scheuer
Theo M. Bestebroer
David F. Burke
Samuel H. Wilks
Monique I. Spronken
Dennis de Meulder
Pascal Lexmond
Mark Pronk
Derek J. Smith
Sander Herfst
Ron A. M. Fouchier
Mathilde Richard
author_sort Adinda Kok
collection DOAJ
description ABSTRACT Avian A/H7 influenza viruses are a global threat to animal and human health. These viruses continue to cause outbreaks in poultry and have caused the highest number of reported zoonotic infections to date, highlighting their pandemic threat. Evidence for antigenic diversification of avian A/H7 influenza viruses exists; however, knowledge of the drivers and molecular basis of antigenic evolution of these viruses is limited. Here, antigenic cartography was used to analyze the global antigenic diversity of A/H7 influenza viruses and to determine the molecular basis of antigenic change in A/H7N9 viruses. A phylogenetic tree based on all available A/H7 HA sequences was generated, from which 52 representative, genetically diverse, antigens were selected for antigenic characterization using hemagglutination inhibition assays. The resulting data were used to compute an antigenic map using multidimensional scaling algorithms. High antigenic relatedness was observed between antigens and sera belonging to genetically divergent A/H7 (sub)lineages. The most striking antigenic change relative to the timespan of virus isolation was observed for the A/H7N9 viruses isolated between 2013 and 2019 in China. Amino acid changes at positions 116, 118, 125, 130, 151, and 217 in the hemagglutinin globular head were found to be the main determinants of antigenic evolution between A/H7N9 influenza virus prototypes. The A/H7 antigenic map and knowledge of the molecular determinants of their antigenic evolution will aid pandemic preparedness against A/H7 influenza viruses, specifically regarding the design of novel vaccines and vaccination strategies. IMPORTANCE A/H7 avian influenza viruses cause outbreaks in poultry globally, resulting in outbreaks with significant socio-economical impact and zoonotic risks. Occasionally, poultry vaccination programs have been implemented to reduce the burden of these viruses, which might result in an increased immune pressure accelerating antigenic evolution. In fact, evidence for antigenic diversification of A/H7 influenza viruses exists, posing challenges to pandemic preparedness and the design of vaccination strategies efficacious against drifted variants. Here, we performed a comprehensive analysis of the global antigenic diversity of A/H7 influenza viruses and identified the main substitutions in the hemagglutinin responsible for antigenic evolution in A/H7N9 viruses isolated between 2013 and 2019. The A/H7 antigenic map and knowledge of the molecular determinants of their antigenic evolution add value to A/H7 influenza virus surveillance programs, the design of vaccines and vaccination strategies, and pandemic preparedness.
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spelling doaj.art-cee182fa3e024fc8917eef1c6f84f1bd2023-11-16T21:48:01ZengAmerican Society for MicrobiologymBio2150-75112023-10-0114510.1128/mbio.00488-23Characterization of A/H7 influenza virus global antigenic diversity and key determinants in the hemagglutinin globular head mediating A/H7N9 antigenic evolutionAdinda Kok0Rachel Scheuer1Theo M. Bestebroer2David F. Burke3Samuel H. Wilks4Monique I. Spronken5Dennis de Meulder6Pascal Lexmond7Mark Pronk8Derek J. Smith9Sander Herfst10Ron A. M. Fouchier11Mathilde Richard12Department of Viroscience, Erasmus Medical Center , Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus Medical Center , Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus Medical Center , Rotterdam, The NetherlandsCenter for Pathogen Evolution, Department of Zoology, University of Cambridge , Cambridge, United KingdomCenter for Pathogen Evolution, Department of Zoology, University of Cambridge , Cambridge, United KingdomDepartment of Viroscience, Erasmus Medical Center , Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus Medical Center , Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus Medical Center , Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus Medical Center , Rotterdam, The NetherlandsCenter for Pathogen Evolution, Department of Zoology, University of Cambridge , Cambridge, United KingdomDepartment of Viroscience, Erasmus Medical Center , Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus Medical Center , Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus Medical Center , Rotterdam, The NetherlandsABSTRACT Avian A/H7 influenza viruses are a global threat to animal and human health. These viruses continue to cause outbreaks in poultry and have caused the highest number of reported zoonotic infections to date, highlighting their pandemic threat. Evidence for antigenic diversification of avian A/H7 influenza viruses exists; however, knowledge of the drivers and molecular basis of antigenic evolution of these viruses is limited. Here, antigenic cartography was used to analyze the global antigenic diversity of A/H7 influenza viruses and to determine the molecular basis of antigenic change in A/H7N9 viruses. A phylogenetic tree based on all available A/H7 HA sequences was generated, from which 52 representative, genetically diverse, antigens were selected for antigenic characterization using hemagglutination inhibition assays. The resulting data were used to compute an antigenic map using multidimensional scaling algorithms. High antigenic relatedness was observed between antigens and sera belonging to genetically divergent A/H7 (sub)lineages. The most striking antigenic change relative to the timespan of virus isolation was observed for the A/H7N9 viruses isolated between 2013 and 2019 in China. Amino acid changes at positions 116, 118, 125, 130, 151, and 217 in the hemagglutinin globular head were found to be the main determinants of antigenic evolution between A/H7N9 influenza virus prototypes. The A/H7 antigenic map and knowledge of the molecular determinants of their antigenic evolution will aid pandemic preparedness against A/H7 influenza viruses, specifically regarding the design of novel vaccines and vaccination strategies. IMPORTANCE A/H7 avian influenza viruses cause outbreaks in poultry globally, resulting in outbreaks with significant socio-economical impact and zoonotic risks. Occasionally, poultry vaccination programs have been implemented to reduce the burden of these viruses, which might result in an increased immune pressure accelerating antigenic evolution. In fact, evidence for antigenic diversification of A/H7 influenza viruses exists, posing challenges to pandemic preparedness and the design of vaccination strategies efficacious against drifted variants. Here, we performed a comprehensive analysis of the global antigenic diversity of A/H7 influenza viruses and identified the main substitutions in the hemagglutinin responsible for antigenic evolution in A/H7N9 viruses isolated between 2013 and 2019. The A/H7 antigenic map and knowledge of the molecular determinants of their antigenic evolution add value to A/H7 influenza virus surveillance programs, the design of vaccines and vaccination strategies, and pandemic preparedness.https://journals.asm.org/doi/10.1128/mbio.00488-23avian influenza virusantigenic evolutionhemagglutininantigenic cartography
spellingShingle Adinda Kok
Rachel Scheuer
Theo M. Bestebroer
David F. Burke
Samuel H. Wilks
Monique I. Spronken
Dennis de Meulder
Pascal Lexmond
Mark Pronk
Derek J. Smith
Sander Herfst
Ron A. M. Fouchier
Mathilde Richard
Characterization of A/H7 influenza virus global antigenic diversity and key determinants in the hemagglutinin globular head mediating A/H7N9 antigenic evolution
mBio
avian influenza virus
antigenic evolution
hemagglutinin
antigenic cartography
title Characterization of A/H7 influenza virus global antigenic diversity and key determinants in the hemagglutinin globular head mediating A/H7N9 antigenic evolution
title_full Characterization of A/H7 influenza virus global antigenic diversity and key determinants in the hemagglutinin globular head mediating A/H7N9 antigenic evolution
title_fullStr Characterization of A/H7 influenza virus global antigenic diversity and key determinants in the hemagglutinin globular head mediating A/H7N9 antigenic evolution
title_full_unstemmed Characterization of A/H7 influenza virus global antigenic diversity and key determinants in the hemagglutinin globular head mediating A/H7N9 antigenic evolution
title_short Characterization of A/H7 influenza virus global antigenic diversity and key determinants in the hemagglutinin globular head mediating A/H7N9 antigenic evolution
title_sort characterization of a h7 influenza virus global antigenic diversity and key determinants in the hemagglutinin globular head mediating a h7n9 antigenic evolution
topic avian influenza virus
antigenic evolution
hemagglutinin
antigenic cartography
url https://journals.asm.org/doi/10.1128/mbio.00488-23
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