Characterization of changes in the hemagglutinin that accompanied the emergence of H3N2/1968 pandemic influenza viruses.

The hemagglutinin (HA) of A/H3N2 pandemic influenza viruses (IAVs) of 1968 differed from its inferred avian precursor by eight amino acid substitutions. To determine their phenotypic effects, we studied recombinant variants of A/Hong Kong/1/1968 virus containing either human-type or avian-type amino...

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Autores principales:	Johanna West, Juliane Röder, Tatyana Matrosovich, Jana Beicht, Jan Baumann, Nancy Mounogou Kouassi, Jennifer Doedt, Nicolai Bovin, Gianpiero Zamperin, Michele Gastaldelli, Annalisa Salviato, Francesco Bonfante, Sergei Kosakovsky Pond, Sander Herfst, Ron Fouchier, Jochen Wilhelm, Hans-Dieter Klenk, Mikhail Matrosovich
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ad99e80ad7a74328bd5aa6c4a8df4cbd
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spelling	oai:doaj.org-article:ad99e80ad7a74328bd5aa6c4a8df4cbd2021-12-02T20:00:07ZCharacterization of changes in the hemagglutinin that accompanied the emergence of H3N2/1968 pandemic influenza viruses.1553-73661553-737410.1371/journal.ppat.1009566https://doaj.org/article/ad99e80ad7a74328bd5aa6c4a8df4cbd2021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009566https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The hemagglutinin (HA) of A/H3N2 pandemic influenza viruses (IAVs) of 1968 differed from its inferred avian precursor by eight amino acid substitutions. To determine their phenotypic effects, we studied recombinant variants of A/Hong Kong/1/1968 virus containing either human-type or avian-type amino acids in the corresponding positions of HA. The precursor HA displayed receptor binding profile and high conformational stability typical for duck IAVs. Substitutions Q226L and G228S, in addition to their known effects on receptor specificity and replication, marginally decreased HA stability. Substitutions R62I, D63N, D81N and N193S reduced HA binding avidity. Substitutions R62I, D81N and A144G promoted viral replication in human airway epithelial cultures. Analysis of HA sequences revealed that substitutions D63N and D81N accompanied by the addition of N-glycans represent common markers of avian H3 HA adaptation to mammals. Our results advance understanding of genotypic and phenotypic changes in IAV HA required for avian-to-human adaptation and pandemic emergence.Johanna WestJuliane RöderTatyana MatrosovichJana BeichtJan BaumannNancy Mounogou KouassiJennifer DoedtNicolai BovinGianpiero ZamperinMichele GastaldelliAnnalisa SalviatoFrancesco BonfanteSergei Kosakovsky PondSander HerfstRon FouchierJochen WilhelmHans-Dieter KlenkMikhail MatrosovichPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 9, p e1009566 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Johanna West Juliane Röder Tatyana Matrosovich Jana Beicht Jan Baumann Nancy Mounogou Kouassi Jennifer Doedt Nicolai Bovin Gianpiero Zamperin Michele Gastaldelli Annalisa Salviato Francesco Bonfante Sergei Kosakovsky Pond Sander Herfst Ron Fouchier Jochen Wilhelm Hans-Dieter Klenk Mikhail Matrosovich Characterization of changes in the hemagglutinin that accompanied the emergence of H3N2/1968 pandemic influenza viruses.
description	The hemagglutinin (HA) of A/H3N2 pandemic influenza viruses (IAVs) of 1968 differed from its inferred avian precursor by eight amino acid substitutions. To determine their phenotypic effects, we studied recombinant variants of A/Hong Kong/1/1968 virus containing either human-type or avian-type amino acids in the corresponding positions of HA. The precursor HA displayed receptor binding profile and high conformational stability typical for duck IAVs. Substitutions Q226L and G228S, in addition to their known effects on receptor specificity and replication, marginally decreased HA stability. Substitutions R62I, D63N, D81N and N193S reduced HA binding avidity. Substitutions R62I, D81N and A144G promoted viral replication in human airway epithelial cultures. Analysis of HA sequences revealed that substitutions D63N and D81N accompanied by the addition of N-glycans represent common markers of avian H3 HA adaptation to mammals. Our results advance understanding of genotypic and phenotypic changes in IAV HA required for avian-to-human adaptation and pandemic emergence.
format	article
author	Johanna West Juliane Röder Tatyana Matrosovich Jana Beicht Jan Baumann Nancy Mounogou Kouassi Jennifer Doedt Nicolai Bovin Gianpiero Zamperin Michele Gastaldelli Annalisa Salviato Francesco Bonfante Sergei Kosakovsky Pond Sander Herfst Ron Fouchier Jochen Wilhelm Hans-Dieter Klenk Mikhail Matrosovich
author_facet	Johanna West Juliane Röder Tatyana Matrosovich Jana Beicht Jan Baumann Nancy Mounogou Kouassi Jennifer Doedt Nicolai Bovin Gianpiero Zamperin Michele Gastaldelli Annalisa Salviato Francesco Bonfante Sergei Kosakovsky Pond Sander Herfst Ron Fouchier Jochen Wilhelm Hans-Dieter Klenk Mikhail Matrosovich
author_sort	Johanna West
title	Characterization of changes in the hemagglutinin that accompanied the emergence of H3N2/1968 pandemic influenza viruses.
title_short	Characterization of changes in the hemagglutinin that accompanied the emergence of H3N2/1968 pandemic influenza viruses.
title_full	Characterization of changes in the hemagglutinin that accompanied the emergence of H3N2/1968 pandemic influenza viruses.
title_fullStr	Characterization of changes in the hemagglutinin that accompanied the emergence of H3N2/1968 pandemic influenza viruses.
title_full_unstemmed	Characterization of changes in the hemagglutinin that accompanied the emergence of H3N2/1968 pandemic influenza viruses.
title_sort	characterization of changes in the hemagglutinin that accompanied the emergence of h3n2/1968 pandemic influenza viruses.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/ad99e80ad7a74328bd5aa6c4a8df4cbd
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Characterization of changes in the hemagglutinin that accompanied the emergence of H3N2/1968 pandemic influenza viruses.

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