Antigenic drift of the pandemic 2009 A(H1N1) influenza virus in a ferret model
- Guarnaccia, Teagan, Carolan, Louise, Maurer-Stroh, Sebastian, Lee, Raphael, Job, Emma, Reading, Patrick, Petrie, Stephen, McCaw, James, McVernon, Jodie, Hurt, Aeron, Kelso, Anne, Mosse, Jennifer, Barr, Ian, Laurie, Karen
- Authors: Guarnaccia, Teagan , Carolan, Louise , Maurer-Stroh, Sebastian , Lee, Raphael , Job, Emma , Reading, Patrick , Petrie, Stephen , McCaw, James , McVernon, Jodie , Hurt, Aeron , Kelso, Anne , Mosse, Jennifer , Barr, Ian , Laurie, Karen
- Date: 2013
- Type: Text , Journal article
- Relation: PLoS Pathogens Vol. 9, no. 5 (2013), p. 1-18
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- 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.
- Authors: Guarnaccia, Teagan , Carolan, Louise , Maurer-Stroh, Sebastian , Lee, Raphael , Job, Emma , Reading, Patrick , Petrie, Stephen , McCaw, James , McVernon, Jodie , Hurt, Aeron , Kelso, Anne , Mosse, Jennifer , Barr, Ian , Laurie, Karen
- Date: 2013
- Type: Text , Journal article
- Relation: PLoS Pathogens Vol. 9, no. 5 (2013), p. 1-18
- Full Text:
- Reviewed:
- 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.
Interval between infections and viral hierarchy are determinants of viral interference following influenza virus infection in a ferret model
- Laurie, Karen, Guarnaccia, Teagan, Carolan, Louise, Yan, Aada, Aban, Malet, Petrie, Stephen, Cao, Pengxing, Heffernan, Jane, McVernon, Jodie, Mosse, Jennifer, Kelso, Anne, McCaw, James, Barr, Ian
- Authors: Laurie, Karen , Guarnaccia, Teagan , Carolan, Louise , Yan, Aada , Aban, Malet , Petrie, Stephen , Cao, Pengxing , Heffernan, Jane , McVernon, Jodie , Mosse, Jennifer , Kelso, Anne , McCaw, James , Barr, Ian
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of Infectious Diseases Vol. 212, no. 10 (2015), p. 1701-1710
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- Description: Background. Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference. Methods. Ferrets were first infected then challenged 1-14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010. Results. Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was <1 week. This effect was virus specific and occurred between antigenically related and unrelated viruses. Coinfections occurred when 1 or 3 days separated infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. Conclusions. The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season.
- Authors: Laurie, Karen , Guarnaccia, Teagan , Carolan, Louise , Yan, Aada , Aban, Malet , Petrie, Stephen , Cao, Pengxing , Heffernan, Jane , McVernon, Jodie , Mosse, Jennifer , Kelso, Anne , McCaw, James , Barr, Ian
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of Infectious Diseases Vol. 212, no. 10 (2015), p. 1701-1710
- Full Text:
- Reviewed:
- Description: Background. Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference. Methods. Ferrets were first infected then challenged 1-14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010. Results. Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was <1 week. This effect was virus specific and occurred between antigenically related and unrelated viruses. Coinfections occurred when 1 or 3 days separated infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. Conclusions. The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season.
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