Open AccessCharacterization of changes in the hemagglutinin that accompanied the emergence of H3N2/1968 pandemic influenza viruses
Author(s) -
Johanna West,
Juliane Röder,
Tatyana Matrosovich,
Jana Beicht,
Jan Baumann,
Nancy Mounogou Kouassi,
Jennifer Doedt,
Nicolai V. Bovin,
Gianpiero Zamperin,
Michele Gastaldelli,
Annalisa Salviato,
Francesco Bonfante,
Sergei L. Kosakovsky Pond,
Sander Herfst,
Ron A. M. Fouchier,
Jochen Wilhelm,
HansDieter Klenk,
Mikhail Matrosovich
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009566
Subject(s) - hemagglutinin (influenza) , biology , virology , avidity , amino acid , virus , viral replication , influenza a virus , phenotype , influenza a virus subtype h5n1 , recombinant dna , genetics , gene , antibody
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.