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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 |
Appears in Collections: | Elements Staff Publications |
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