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Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model
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 th...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649996/ https://www.ncbi.nlm.nih.gov/pubmed/23671418 http://dx.doi.org/10.1371/journal.ppat.1003354 |
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author | Guarnaccia, Teagan Carolan, Louise A. Maurer-Stroh, Sebastian Lee, Raphael T. C. Job, Emma Reading, Patrick C. Petrie, Stephen McCaw, James M. McVernon, Jodie Hurt, Aeron C. Kelso, Anne Mosse, Jennifer Barr, Ian G. Laurie, Karen L. |
author_facet | Guarnaccia, Teagan Carolan, Louise A. Maurer-Stroh, Sebastian Lee, Raphael T. C. Job, Emma Reading, Patrick C. Petrie, Stephen McCaw, James M. McVernon, Jodie Hurt, Aeron C. Kelso, Anne Mosse, Jennifer Barr, Ian G. Laurie, Karen L. |
author_sort | Guarnaccia, Teagan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3649996 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36499962013-05-13 Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model Guarnaccia, Teagan Carolan, Louise A. Maurer-Stroh, Sebastian Lee, Raphael T. C. Job, Emma Reading, Patrick C. Petrie, Stephen McCaw, James M. McVernon, Jodie Hurt, Aeron C. Kelso, Anne Mosse, Jennifer Barr, Ian G. Laurie, Karen L. PLoS Pathog Research Article 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. Public Library of Science 2013-05-09 /pmc/articles/PMC3649996/ /pubmed/23671418 http://dx.doi.org/10.1371/journal.ppat.1003354 Text en © 2013 Guarnaccia et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Guarnaccia, Teagan Carolan, Louise A. Maurer-Stroh, Sebastian Lee, Raphael T. C. Job, Emma Reading, Patrick C. Petrie, Stephen McCaw, James M. McVernon, Jodie Hurt, Aeron C. Kelso, Anne Mosse, Jennifer Barr, Ian G. Laurie, Karen L. Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model |
title | Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model |
title_full | Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model |
title_fullStr | Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model |
title_full_unstemmed | Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model |
title_short | Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model |
title_sort | antigenic drift of the pandemic 2009 a(h1n1) influenza virus in a ferret model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649996/ https://www.ncbi.nlm.nih.gov/pubmed/23671418 http://dx.doi.org/10.1371/journal.ppat.1003354 |
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