Cell-Culture Adaptation of H3N2 Influenza Virus Impacts Acid Stability and Reduces Airborne Transmission in Ferret Model.
Adaptation, Physiological
Animals
Cell Culture Techniques
Cell Line
Cells, Cultured
Disease Models, Animal
Ferrets
/ virology
Hemagglutinin Glycoproteins, Influenza Virus
/ genetics
Hydrogen-Ion Concentration
Influenza A Virus, H3N2 Subtype
/ physiology
Mutation
Orthomyxoviridae Infections
/ transmission
Untranslated Regions
Virus Replication
hemagglutinin
influenza virus
pH
transmission
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
21 04 2021
21 04 2021
Historique:
received:
09
03
2021
revised:
11
04
2021
accepted:
14
04
2021
entrez:
30
4
2021
pubmed:
1
5
2021
medline:
18
8
2021
Statut:
epublish
Résumé
Airborne transmission of seasonal and pandemic influenza viruses is the reason for their epidemiological success and public health burden in humans. Efficient airborne transmission of the H1N1 influenza virus relies on the receptor specificity and pH of fusion of the surface glycoprotein hemagglutinin (HA). In this study, we examined the role of HA pH of fusion on transmissibility of a cell-culture-adapted H3N2 virus. Mutations in the HA head at positions 78 and 212 of A/Perth/16/2009 (H3N2), which were selected after cell culture adaptation, decreased the acid stability of the virus from pH 5.5 (WT) to pH 5.8 (mutant). In addition, the mutant H3N2 virus replicated to higher titers in cell culture but had reduced airborne transmission in the ferret model. These data demonstrate that, like H1N1 HA, the pH of fusion for H3N2 HA is a determinant of efficient airborne transmission. Surprisingly, noncoding regions of the NA segment can impact the pH of fusion of mutant viruses. Taken together, our data confirm that HA acid stability is an important characteristic of epidemiologically successful human influenza viruses and is influenced by HA/NA balance.
Identifiants
pubmed: 33919124
pii: v13050719
doi: 10.3390/v13050719
pmc: PMC8143181
pii:
doi:
Substances chimiques
Hemagglutinin Glycoproteins, Influenza Virus
0
Untranslated Regions
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
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI139063
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201400007C
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI127893
Pays : United States
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