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.
MDCK-SIAT1 cells show improved isolation rates for recent human influenza viruses compared to conventinal MDCK cells
- Oh, Ding, Barr, Ian, Mosse, Jennifer, Laurie, Karen
- Authors: Oh, Ding , Barr, Ian , Mosse, Jennifer , Laurie, Karen
- Date: 2008
- Type: Text , Journal article
- Relation: Journal of Clinical Microbiology Vol. 46, no. 7 (2008), p. 2189-2194
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- Description: The ability to isolate and propagate influenza virus is an essential tool for the yearly surveillance of circulating virus strains and to ensure accurate clinical diagnosis for appropriate treatment. The suitability of MDCK-SIAT1 cells, engineered to express increased levels of alpha-2,6-linked sialic acid receptors, as an alternative to conventional MDCK cells for isolation of circulating influenza virus was assessed. A greater number of influenza A (H1N1 and H3N2) and B viruses from stored human clinical specimens collected between 2005 and 2007 were isolated following inoculation in MDCK-SIAT1 cells than in MDCK cells. In addition, a higher titer of virus was recovered following culture in MDCK-SIAT1 cells. All A(H1N1) viruses recovered from MDCK-SIAT1 cells were able to agglutinate both turkey and guinea pig red blood cells (RBC), while half of the A(H3N2) viruses recovered after passage in MDCK-SIAT1 cells lost the ability to agglutinate turkey RBC. Importantly, the HA-1 domain of the hemagglutinin gene was genetically stable after passaging in MDCK-SIAT1 cells, a feature not always seen following MDCK cell or embryonated chicken egg passage of human influenza virus. These data indicate that the MDCK-SIAT1 cell line is superior to conventional MDCK cells for isolation of human influenza virus from clinical specimens and may be used routinely for the isolation and propagation of current human influenza viruses for surveillance, diagnostic, and research purposes.
- Authors: Oh, Ding , Barr, Ian , Mosse, Jennifer , Laurie, Karen
- Date: 2008
- Type: Text , Journal article
- Relation: Journal of Clinical Microbiology Vol. 46, no. 7 (2008), p. 2189-2194
- Full Text:
- Reviewed:
- Description: The ability to isolate and propagate influenza virus is an essential tool for the yearly surveillance of circulating virus strains and to ensure accurate clinical diagnosis for appropriate treatment. The suitability of MDCK-SIAT1 cells, engineered to express increased levels of alpha-2,6-linked sialic acid receptors, as an alternative to conventional MDCK cells for isolation of circulating influenza virus was assessed. A greater number of influenza A (H1N1 and H3N2) and B viruses from stored human clinical specimens collected between 2005 and 2007 were isolated following inoculation in MDCK-SIAT1 cells than in MDCK cells. In addition, a higher titer of virus was recovered following culture in MDCK-SIAT1 cells. All A(H1N1) viruses recovered from MDCK-SIAT1 cells were able to agglutinate both turkey and guinea pig red blood cells (RBC), while half of the A(H3N2) viruses recovered after passage in MDCK-SIAT1 cells lost the ability to agglutinate turkey RBC. Importantly, the HA-1 domain of the hemagglutinin gene was genetically stable after passaging in MDCK-SIAT1 cells, a feature not always seen following MDCK cell or embryonated chicken egg passage of human influenza virus. These data indicate that the MDCK-SIAT1 cell line is superior to conventional MDCK cells for isolation of human influenza virus from clinical specimens and may be used routinely for the isolation and propagation of current human influenza viruses for surveillance, diagnostic, and research purposes.
Zanamivir-resistant influenza viruses with Q136K or Q136R neuraminidase residue mutations can arise during MDCK cell culture creating challenges for antiviral susceptibility monitoring
- Little, Karen, Leang, Sookkwan, Butler, Jeff, Baas, Chantal, Harrower, Bruce, Mosse, Jennifer, Barr, Ian, Hurt, Aeron
- Authors: Little, Karen , Leang, Sookkwan , Butler, Jeff , Baas, Chantal , Harrower, Bruce , Mosse, Jennifer , Barr, Ian , Hurt, Aeron
- Date: 2015
- Type: Text , Journal article
- Relation: Eurosurveillance Vol. 20, no. 45 (2015), p.
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- Description: Surveillance of circulating influenza strains for antiviral susceptibility is important to ensure patient treatment guidelines remain appropriate. Influenza A(H3N2) and A(H1N1)pdm09 virus isolates containing mutations at the Q136 residue of the neuraminidase (NA) that conferred reduced susceptibility to the NA inhibitor (NAI) zanamivir were detected during antiviral susceptibility monitoring. Interestingly, the mutations were not detectable in the viruses from respective clinical specimens, only in the cultured isolates. We showed that variant viruses containing the Q136K and Q136R NA mutations were preferentially selected in Madin-Darby canine kidney epithelial (MDCK) cells, but were less well supported in MDCK-SIAT1 cells and embryonated eggs. The effect of Q136K, Q136R, Q136H and Q136L substitutions in NA subtypes N1 and N2 on NAI susceptibility and in vitro viral fitness was assessed. This study highlights the challenges that cell culture derived mutations can pose to the NAI susceptibility analysis and interpretation and reaffirms the need to sequence viruses from respective clinical specimens to avoid misdiagnosis. However, we also demonstrate that NA mutations at residue136 can confer reduced zanamivir, peramivir or laninamivir susceptibility, and therefore close monitoring of viruses for mutations at this site from patients being treated with these antivirals is important.
- Authors: Little, Karen , Leang, Sookkwan , Butler, Jeff , Baas, Chantal , Harrower, Bruce , Mosse, Jennifer , Barr, Ian , Hurt, Aeron
- Date: 2015
- Type: Text , Journal article
- Relation: Eurosurveillance Vol. 20, no. 45 (2015), p.
- Full Text:
- Reviewed:
- Description: Surveillance of circulating influenza strains for antiviral susceptibility is important to ensure patient treatment guidelines remain appropriate. Influenza A(H3N2) and A(H1N1)pdm09 virus isolates containing mutations at the Q136 residue of the neuraminidase (NA) that conferred reduced susceptibility to the NA inhibitor (NAI) zanamivir were detected during antiviral susceptibility monitoring. Interestingly, the mutations were not detectable in the viruses from respective clinical specimens, only in the cultured isolates. We showed that variant viruses containing the Q136K and Q136R NA mutations were preferentially selected in Madin-Darby canine kidney epithelial (MDCK) cells, but were less well supported in MDCK-SIAT1 cells and embryonated eggs. The effect of Q136K, Q136R, Q136H and Q136L substitutions in NA subtypes N1 and N2 on NAI susceptibility and in vitro viral fitness was assessed. This study highlights the challenges that cell culture derived mutations can pose to the NAI susceptibility analysis and interpretation and reaffirms the need to sequence viruses from respective clinical specimens to avoid misdiagnosis. However, we also demonstrate that NA mutations at residue136 can confer reduced zanamivir, peramivir or laninamivir susceptibility, and therefore close monitoring of viruses for mutations at this site from patients being treated with these antivirals is important.
Influenza A(H5N1) viruses with A(H9N2) single gene (matrix or PB1) reassortment isolated from Cambodian live bird markets
- Suttie, Annika, Karlsson, Erik, Deng, Yi-Mo, Horm, Srey, Yann, Sokhoun, Tok, Songha, Sorn, San, Holl, Davun, Tum, Sothyra, Hurt, Aeron, Greenhill, Andrew, Barr, Ian, Horwood, Paul, Dussart, Philippe
- Authors: Suttie, Annika , Karlsson, Erik , Deng, Yi-Mo , Horm, Srey , Yann, Sokhoun , Tok, Songha , Sorn, San , Holl, Davun , Tum, Sothyra , Hurt, Aeron , Greenhill, Andrew , Barr, Ian , Horwood, Paul , Dussart, Philippe
- Date: 2018
- Type: Text , Journal article
- Relation: Virology Vol. 523, no. (2018), p. 22-26
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- Description: Live bird market surveillance for avian influenza viruses in Cambodia in 2015 has led to the detection of two 7:1 reassortant influenza A(H5N1) clade 2.3.2.1c viruses. These reassortant strains, designated A/duck/Cambodia/Z564W35M1/2015 and A/chicken/Cambodia/Z850W49M1/2015, both contained a single gene (PB1 and matrix gene, respectively) from concurrently circulating A(H9N2) influenza viruses. All other viral genes from both isolates clustered with A(H5N1) clade 2.3.2.1 viruses. Continued and prolonged co-circulation of influenza A(H5N1) and A(H9N2) viruses in Cambodian live bird markets may present a risk for the emergence of novel influenza reassortant viruses with negative agricultural and/or public health implications. © 2018
- Authors: Suttie, Annika , Karlsson, Erik , Deng, Yi-Mo , Horm, Srey , Yann, Sokhoun , Tok, Songha , Sorn, San , Holl, Davun , Tum, Sothyra , Hurt, Aeron , Greenhill, Andrew , Barr, Ian , Horwood, Paul , Dussart, Philippe
- Date: 2018
- Type: Text , Journal article
- Relation: Virology Vol. 523, no. (2018), p. 22-26
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- Reviewed:
- Description: Live bird market surveillance for avian influenza viruses in Cambodia in 2015 has led to the detection of two 7:1 reassortant influenza A(H5N1) clade 2.3.2.1c viruses. These reassortant strains, designated A/duck/Cambodia/Z564W35M1/2015 and A/chicken/Cambodia/Z850W49M1/2015, both contained a single gene (PB1 and matrix gene, respectively) from concurrently circulating A(H9N2) influenza viruses. All other viral genes from both isolates clustered with A(H5N1) clade 2.3.2.1 viruses. Continued and prolonged co-circulation of influenza A(H5N1) and A(H9N2) viruses in Cambodian live bird markets may present a risk for the emergence of novel influenza reassortant viruses with negative agricultural and/or public health implications. © 2018
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.
SARS-CoV-2 does not replicate in embryonated hen's eggs or in MDCK cell lines
- Barr, Ian, Rynehart, Cleve, Whitney, Paul, Druce, Julian
- Authors: Barr, Ian , Rynehart, Cleve , Whitney, Paul , Druce, Julian
- Date: 2020
- Type: Text , Journal article
- Relation: Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin Vol. 25, no. 25 (2020), p.
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- Description: The advent of COVID-19, has posed a risk that human respiratory samples containing human influenza viruses may also contain SARS-CoV-2. This potential risk may lead to SARS-CoV-2 contaminating conventional influenza vaccine production platforms as respiratory samples are used to directly inoculate embryonated hen's eggs and continuous cell lines that are used to isolate and produce influenza vaccines. We investigated the ability of these substrates to propagate SARS-CoV-2 and found that neither could support SARS-CoV-2 replication.
- Authors: Barr, Ian , Rynehart, Cleve , Whitney, Paul , Druce, Julian
- Date: 2020
- Type: Text , Journal article
- Relation: Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin Vol. 25, no. 25 (2020), p.
- Full Text:
- Reviewed:
- Description: The advent of COVID-19, has posed a risk that human respiratory samples containing human influenza viruses may also contain SARS-CoV-2. This potential risk may lead to SARS-CoV-2 contaminating conventional influenza vaccine production platforms as respiratory samples are used to directly inoculate embryonated hen's eggs and continuous cell lines that are used to isolate and produce influenza vaccines. We investigated the ability of these substrates to propagate SARS-CoV-2 and found that neither could support SARS-CoV-2 replication.
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