Characterization of changes in the hemagglutinin that accompanied the emergence of H3N2/1968 pandemic influenza viruses.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
22
04
2021
accepted:
04
09
2021
revised:
05
10
2021
pubmed:
24
9
2021
medline:
25
11
2021
entrez:
23
9
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34555124
doi: 10.1371/journal.ppat.1009566
pii: PPATHOGENS-D-21-00869
pmc: PMC8491938
doi:
Substances chimiques
Hemagglutinin Glycoproteins, Influenza Virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009566Subventions
Organisme : NIAID NIH HHS
ID : HHSN272201400008C
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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