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PLoS ONE. Preexisting CD4+ T-Cell Immunity in Human Population to Avian Influenza H7N9 Virus: Whole Proteome-Wide Immunoinformatics Analyses
[Source: PLoS ONE, full page: (LINK). Abstract, edited.]
Open Access / Peer-Reviewed / Research Article
Preexisting CD4+ T-Cell Immunity in Human Population to Avian Influenza H7N9 Virus: Whole Proteome-Wide Immunoinformatics Analyses
Venkata R. Duvvuri, Bhargavi Duvvuri, Christilda Alice, Gillian E. Wu, Jonathan B. Gubbay, Jianhong Wu
Published: March 07, 2014 / DOI: 10.1371/journal.pone.0091273
Abstract
In 2013, a novel avian influenza H7N9 virus was identified in human in China. The antigenically distinct H7N9 surface glycoproteins raised concerns about lack of cross-protective neutralizing antibodies. Epitope-specific preexisting T-cell immunity was one of the protective mechanisms in pandemic 2009 H1N1 even in the absence of cross-protective antibodies. Hence, the assessment of preexisting CD4+ T-cell immunity to conserved epitopes shared between H7N9 and human influenza A viruses (IAV) is critical. A comparative whole proteome-wide immunoinformatics analysis was performed to predict the CD4+ T-cell epitopes that are commonly conserved within the proteome of H7N9 in reference to IAV subtypes (H1N1, H2N2, and H3N2). The CD4+ T-cell epitopes that are commonly conserved (~556) were further screened against the Immune Epitope Database (IEDB) to validate their immunogenic potential. This analysis revealed that 45.5% (253 of 556) epitopes are experimentally proven to induce CD4+ T-cell memory responses. In addition, we also found that 23.3% of CD4+ T-cell epitopes have ≥90% of sequence homology with experimentally defined CD8+ T-cell epitopes. We also conducted the population coverage analysis across different ethnicities using commonly conserved CD4+ T-cell epitopes and corresponding HLA-DRB1 alleles. Interestingly, the indigenous populations from Canada, United States, Mexico and Australia exhibited low coverage (28.65% to 45.62%) when compared with other ethnicities (57.77% to 94.84%). In summary, the present analysis demonstrate an evidence on the likely presence of preexisting T-cell immunity in human population and also shed light to understand the potential risk of H7N9 virus among indigenous populations, given their high susceptibility during previous pandemic influenza events. This information is crucial for public health policy, in targeting priority groups for immunization programs.
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Citation: Duvvuri VR, Duvvuri B, Alice C, Wu GE, Gubbay JB, et al. (2014) Preexisting CD4+ T-Cell Immunity in Human Population to Avian Influenza H7N9 Virus: Whole Proteome-Wide Immunoinformatics Analyses. PLoS ONE 9(3): e91273. doi:10.1371/journal.pone.0091273
Editor: Paul G. Thomas, St. Jude Children's Research Hospital, United States of America
Received: October 28, 2013; Accepted: February 9, 2014; Published: March 7, 2014
Copyright: ? 2014 Duvvuri et al. 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 credited.
Funding: This work was supported by the Canada Research Chairs program, The Natural Sciences and Engineering Research Council of Canada and International Development Research Centre. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: JBG has received research grants from GlaxoSmithKline Inc. and Hoffman-La Roche Ltd to study antiviral resistance in influenza; however, these activities are not relevant to this study. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. All the other authors declared that they have no competing interests.
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Open Access / Peer-Reviewed / Research Article
Preexisting CD4+ T-Cell Immunity in Human Population to Avian Influenza H7N9 Virus: Whole Proteome-Wide Immunoinformatics Analyses
Venkata R. Duvvuri, Bhargavi Duvvuri, Christilda Alice, Gillian E. Wu, Jonathan B. Gubbay, Jianhong Wu
Published: March 07, 2014 / DOI: 10.1371/journal.pone.0091273
Abstract
In 2013, a novel avian influenza H7N9 virus was identified in human in China. The antigenically distinct H7N9 surface glycoproteins raised concerns about lack of cross-protective neutralizing antibodies. Epitope-specific preexisting T-cell immunity was one of the protective mechanisms in pandemic 2009 H1N1 even in the absence of cross-protective antibodies. Hence, the assessment of preexisting CD4+ T-cell immunity to conserved epitopes shared between H7N9 and human influenza A viruses (IAV) is critical. A comparative whole proteome-wide immunoinformatics analysis was performed to predict the CD4+ T-cell epitopes that are commonly conserved within the proteome of H7N9 in reference to IAV subtypes (H1N1, H2N2, and H3N2). The CD4+ T-cell epitopes that are commonly conserved (~556) were further screened against the Immune Epitope Database (IEDB) to validate their immunogenic potential. This analysis revealed that 45.5% (253 of 556) epitopes are experimentally proven to induce CD4+ T-cell memory responses. In addition, we also found that 23.3% of CD4+ T-cell epitopes have ≥90% of sequence homology with experimentally defined CD8+ T-cell epitopes. We also conducted the population coverage analysis across different ethnicities using commonly conserved CD4+ T-cell epitopes and corresponding HLA-DRB1 alleles. Interestingly, the indigenous populations from Canada, United States, Mexico and Australia exhibited low coverage (28.65% to 45.62%) when compared with other ethnicities (57.77% to 94.84%). In summary, the present analysis demonstrate an evidence on the likely presence of preexisting T-cell immunity in human population and also shed light to understand the potential risk of H7N9 virus among indigenous populations, given their high susceptibility during previous pandemic influenza events. This information is crucial for public health policy, in targeting priority groups for immunization programs.
_____
Citation: Duvvuri VR, Duvvuri B, Alice C, Wu GE, Gubbay JB, et al. (2014) Preexisting CD4+ T-Cell Immunity in Human Population to Avian Influenza H7N9 Virus: Whole Proteome-Wide Immunoinformatics Analyses. PLoS ONE 9(3): e91273. doi:10.1371/journal.pone.0091273
Editor: Paul G. Thomas, St. Jude Children's Research Hospital, United States of America
Received: October 28, 2013; Accepted: February 9, 2014; Published: March 7, 2014
Copyright: ? 2014 Duvvuri et al. 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 credited.
Funding: This work was supported by the Canada Research Chairs program, The Natural Sciences and Engineering Research Council of Canada and International Development Research Centre. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: JBG has received research grants from GlaxoSmithKline Inc. and Hoffman-La Roche Ltd to study antiviral resistance in influenza; however, these activities are not relevant to this study. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. All the other authors declared that they have no competing interests.
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