Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.ppat.1003354
Title: Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model
Authors: Guarnaccia T.
Carolan L.A.
Maurer-Stroh S. 
Lee R.T.C.
Job E.
Reading P.C.
Petrie S.
McCaw J.M.
McVernon J.
Hurt A.C.
Kelso A.
Mosse J.
Barr I.G.
Laurie K.L.
Keywords: complementary DNA
glycan
2009 H1N1 influenza
amino acid substitution
animal experiment
animal model
animal tissue
antigenicity
article
cloning
controlled study
disease surveillance
female
ferret
flow cytometry
gene sequence
genetic analysis
genetic drift
genetic variability
hemagglutination inhibition test
male
nonhuman
nucleotide sequence
pyrosequencing
real time polymerase chain reaction
reverse transcription polymerase chain reaction
virus infection
virus transmission
Amino Acid Substitution
Animals
Antigens, Viral
Chick Embryo
Disease Models, Animal
Dogs
Female
Ferrets
Genetic Drift
Humans
Influenza A Virus, H1N1 Subtype
Influenza, Human
Madin Darby Canine Kidney Cells
Male
Mutation, Missense
Pandemics
Mustela
Orthomyxoviridae
Issue Date: 2013
Citation: Guarnaccia T., Carolan L.A., Maurer-Stroh S., Lee R.T.C., Job E., Reading P.C., Petrie S., McCaw J.M., McVernon J., Hurt A.C., Kelso A., Mosse J., Barr I.G., Laurie K.L. (2013). Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model. PLoS Pathogens 9 (5) : e1003354. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.ppat.1003354
Rights: Attribution 4.0 International
Abstract: Surveillance data indicate that most circulating A(H1N1)pdm09 influenza viruses have remained antigenically similar since they emerged in humans in 2009. However, antigenic drift is likely to occur in the future in response to increasing population immunity induced by infection or vaccination. In this study, sequential passaging of A(H1N1)pdm09 virus by contact transmission through two independent series of suboptimally vaccinated ferrets resulted in selection of variant viruses with an amino acid substitution (N156K, H1 numbering without signal peptide; N159K, H3 numbering without signal peptide; N173K, H1 numbering from first methionine) in a known antigenic site of the viral HA. The N156K HA variant replicated and transmitted efficiently between naïve ferrets and outgrew wildtype virus in vivo in ferrets in the presence and absence of immune pressure. In vitro, in a range of cell culture systems, the N156K variant rapidly adapted, acquiring additional mutations in the viral HA that also potentially affected antigenic properties. The N156K escape mutant was antigenically distinct from wildtype virus as shown by binding of HA-specific antibodies. Glycan binding assays demonstrated the N156K escape mutant had altered receptor binding preferences compared to wildtype virus, which was supported by computational modeling predictions. The N156K substitution, and culture adaptations, have been detected in human A(H1N1)pdm09 viruses with N156K preferentially reported in sequences from original clinical samples rather than cultured isolates. This study demonstrates the ability of the A(H1N1)pdm09 virus to undergo rapid antigenic change to evade a low level vaccine response, while remaining fit in a ferret transmission model of immunization and infection. Furthermore, the potential changes in receptor binding properties that accompany antigenic changes highlight the importance of routine characterization of clinical samples in human A(H1N1)pdm09 influenza surveillance. © 2013 Guarnaccia et al.
Source Title: PLoS Pathogens
URI: https://scholarbank.nus.edu.sg/handle/10635/161622
ISSN: 15537366
DOI: 10.1371/journal.ppat.1003354
Rights: Attribution 4.0 International
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