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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| creator | West, Johanna Röder, Juliane Matrosovich, Tatyana Beicht, Jana Baumann, Jan Mounogou Kouassi, Nancy Doedt, Jennifer Bovin, Nicolai Zamperin, Gianpiero Gastaldelli, Michele Salviato, Annalisa Bonfante, Francesco Kosakovsky Pond, Sergei Herfst, Sander Fouchier, Ron Wilhelm, Jochen Klenk, Hans-Dieter Matrosovich, Mikhail |
| 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. |
| doi_str_mv | 10.1371/journal.ppat.1009566 |
| format | Article |
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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.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1009566</identifier><identifier>PMID: 34555124</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Adaptation ; Amino acids ; Aquatic birds ; Avidity ; Binding ; Binding sites ; Biology and life sciences ; Birds ; Causes of ; Efficiency ; Epidemics ; Genetic aspects ; Glycoproteins ; Hemagglutinins ; Influenza ; Influenza viruses ; Medicine and health sciences ; N-glycans ; Orthomyxoviridae ; Pandemics ; Peptides ; Physical Sciences ; Physiological aspects ; Polysaccharides ; Precursors ; Receptors ; Replication ; Research and Analysis Methods ; Russia ; Stability ; Viruses ; Zoonoses</subject><ispartof>PLoS pathogens, 2021-09, Vol.17 (9), p.e1009566-e1009566</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 West et al. 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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. 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pathogens</jtitle><date>2021-09-23</date><risdate>2021</risdate><volume>17</volume><issue>9</issue><spage>e1009566</spage><epage>e1009566</epage><pages>e1009566-e1009566</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>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. 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| subjects | Adaptation Amino acids Aquatic birds Avidity Binding Binding sites Biology and life sciences Birds Causes of Efficiency Epidemics Genetic aspects Glycoproteins Hemagglutinins Influenza Influenza viruses Medicine and health sciences N-glycans Orthomyxoviridae Pandemics Peptides Physical Sciences Physiological aspects Polysaccharides Precursors Receptors Replication Research and Analysis Methods Russia Stability Viruses Zoonoses |
| title | Characterization of changes in the hemagglutinin that accompanied the emergence of H3N2/1968 pandemic influenza viruses |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T04%3A11%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Characterization%20of%20changes%20in%20the%20hemagglutinin%20that%20accompanied%20the%20emergence%20of%20H3N2/1968%20pandemic%20influenza%20viruses&rft.jtitle=PLoS%20pathogens&rft.au=West,%20Johanna&rft.date=2021-09-23&rft.volume=17&rft.issue=9&rft.spage=e1009566&rft.epage=e1009566&rft.pages=e1009566-e1009566&rft.issn=1553-7374&rft.eissn=1553-7374&rft_id=info:doi/10.1371/journal.ppat.1009566&rft_dat=%3Cgale_plos_%3EA677503069%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2582586819&rft_id=info:pmid/34555124&rft_galeid=A677503069&rft_doaj_id=oai_doaj_org_article_ad99e80ad7a74328bd5aa6c4a8df4cbd&rfr_iscdi=true |