Influenza A H1N1 Pandemic Strain Evolution – Divergence and the Potential for Antigenic Drift Variants
Identifieur interne : 000D75 ( Pmc/Curation ); précédent : 000D74; suivant : 000D76Influenza A H1N1 Pandemic Strain Evolution – Divergence and the Potential for Antigenic Drift Variants
Auteurs : Eili Y. Klein [États-Unis] ; Adrian W. R. Serohijos [États-Unis] ; Jeong-Mo Choi [États-Unis] ; Eugene I. Shakhnovich [États-Unis] ; Andrew Pekosz [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2014.
Abstract
The emergence of a novel A(H1N1) strain in 2009 was the first influenza pandemic of the genomic age, and unprecedented surveillance of the virus provides the opportunity to better understand the evolution of influenza. We examined changes in the nucleotide coding regions and the amino acid sequences of the hemagglutinin (HA), neuraminidase (NA), and nucleoprotein (NP) segments of the A(H1N1)pdm09 strain using publicly available data. We calculated the nucleotide and amino acid hamming distance from the vaccine strain A/California/07/2009 for each sequence. We also estimated
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DOI: 10.1371/journal.pone.0093632
PubMed: 24699432
PubMed Central: 3974778
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<front><div type="abstract" xml:lang="en"><p>The emergence of a novel A(H1N1) strain in 2009 was the first influenza pandemic of the genomic age, and unprecedented surveillance of the virus provides the opportunity to better understand the evolution of influenza. We examined changes in the nucleotide coding regions and the amino acid sequences of the hemagglutinin (HA), neuraminidase (NA), and nucleoprotein (NP) segments of the A(H1N1)pdm09 strain using publicly available data. We calculated the nucleotide and amino acid hamming distance from the vaccine strain A/California/07/2009 for each sequence. We also estimated <italic>P<sub>epitope</sub>
</italic>
–a measure of antigenic diversity based on changes in the epitope regions–for each isolate. Finally, we compared our results to A(H3N2) strains collected over the same period. Our analysis found that the mean hamming distance for the HA protein of the A(H1N1)pdm09 strain increased from 3.6 (standard deviation [SD]: 1.3) in 2009 to 11.7 (SD: 1.0) in 2013, while the mean hamming distance in the coding region increased from 7.4 (SD: 2.2) in 2009 to 28.3 (SD: 2.1) in 2013. These trends are broadly similar to the rate of mutation in H3N2 over the same time period. However, in contrast to H3N2 strains, the rate of mutation accumulation has slowed in recent years. Our results are notable because, over the course of the study, mutation rates in H3N2 similar to that seen with A(H1N1)pdm09 led to the emergence of two antigenic drift variants. However, while there has been an H1N1 epidemic in North America this season, evidence to date indicates the vaccine is still effective, suggesting the epidemic is not due to the emergence of an antigenic drift variant. Our results suggest that more research is needed to understand how viral mutations are related to vaccine effectiveness so that future vaccine choices and development can be more predictive.</p>
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<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline-v2"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Evolutionary Biology</subject>
<subj-group><subject>Organismal Evolution</subject>
<subj-group><subject>Microbial Evolution</subject>
<subj-group><subject>Viral Evolution</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group><subject>Microbiology</subject>
<subj-group><subject>Virology</subject>
<subj-group><subject>Viral Vaccines</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v2"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Infectious Diseases</subject>
<subj-group><subject>Viral Diseases</subject>
<subj-group><subject>Influenza</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Influenza A H1N1 Pandemic Strain Evolution – Divergence and the Potential for Antigenic Drift Variants</article-title>
<alt-title alt-title-type="running-head">Influenza A(H1N1) Evolutionary Divergence</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Klein</surname>
<given-names>Eili Y.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>*</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Serohijos</surname>
<given-names>Adrian W. R.</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Choi</surname>
<given-names>Jeong-Mo</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Shakhnovich</surname>
<given-names>Eugene I.</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pekosz</surname>
<given-names>Andrew</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label>
<addr-line>Center for Advanced Modeling in the Social, Behavioral, and Health Sciences, Department of Emergency Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America</addr-line>
</aff>
<aff id="aff2"><label>2</label>
<addr-line>Center for Disease Dynamics, Economics, and Policy, Washington, DC, United States of America</addr-line>
</aff>
<aff id="aff3"><label>3</label>
<addr-line>Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States of America</addr-line>
</aff>
<aff id="aff4"><label>4</label>
<addr-line>W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland, United States of America</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Viboud</surname>
<given-names>Cécile</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1"><addr-line>National Institutes of Health, United States of America</addr-line>
</aff>
<author-notes><corresp id="cor1">* E-mail: <email>eklein@jhu.edu</email>
</corresp>
<fn fn-type="COI-statement"><p><bold>Competing Interests: </bold>
AP is an associate editor at PLOS Pathogens. This does not alter adherence to all PLOS policies on sharing data and materials. All other authors have declared that no competing interests exist.</p>
</fn>
<fn fn-type="con"><p>Conceived and designed the experiments: EYK JMC AWRS. Performed the experiments: EYK JMC AWRS. Analyzed the data: EYK JMC AWRS. Wrote the paper: EYK JMC AWRS EIS AP.</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><year>2014</year>
</pub-date>
<pub-date pub-type="epub"><day>3</day>
<month>4</month>
<year>2014</year>
</pub-date>
<volume>9</volume>
<issue>4</issue>
<elocation-id>e93632</elocation-id>
<history><date date-type="received"><day>7</day>
<month>1</month>
<year>2014</year>
</date>
<date date-type="accepted"><day>4</day>
<month>3</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>© 2014 Klein et al</copyright-statement>
<copyright-year>2014</copyright-year>
<copyright-holder>Klein et al</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>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.</license-p>
</license>
</permissions>
<abstract><p>The emergence of a novel A(H1N1) strain in 2009 was the first influenza pandemic of the genomic age, and unprecedented surveillance of the virus provides the opportunity to better understand the evolution of influenza. We examined changes in the nucleotide coding regions and the amino acid sequences of the hemagglutinin (HA), neuraminidase (NA), and nucleoprotein (NP) segments of the A(H1N1)pdm09 strain using publicly available data. We calculated the nucleotide and amino acid hamming distance from the vaccine strain A/California/07/2009 for each sequence. We also estimated <italic>P<sub>epitope</sub>
</italic>
–a measure of antigenic diversity based on changes in the epitope regions–for each isolate. Finally, we compared our results to A(H3N2) strains collected over the same period. Our analysis found that the mean hamming distance for the HA protein of the A(H1N1)pdm09 strain increased from 3.6 (standard deviation [SD]: 1.3) in 2009 to 11.7 (SD: 1.0) in 2013, while the mean hamming distance in the coding region increased from 7.4 (SD: 2.2) in 2009 to 28.3 (SD: 2.1) in 2013. These trends are broadly similar to the rate of mutation in H3N2 over the same time period. However, in contrast to H3N2 strains, the rate of mutation accumulation has slowed in recent years. Our results are notable because, over the course of the study, mutation rates in H3N2 similar to that seen with A(H1N1)pdm09 led to the emergence of two antigenic drift variants. However, while there has been an H1N1 epidemic in North America this season, evidence to date indicates the vaccine is still effective, suggesting the epidemic is not due to the emergence of an antigenic drift variant. Our results suggest that more research is needed to understand how viral mutations are related to vaccine effectiveness so that future vaccine choices and development can be more predictive.</p>
</abstract>
<funding-group><funding-statement>Funding was provided by the Defense Advanced Research Projects Agency through grant HR0011-11-C-0093 and by the Models of Infectious Disease Agent Study (MIDAS), under Award Number U01GM070708 from the National Institutes of General Medical Sciences, as well as a National Institutes of Health Pioneer Award (DP1OD003874). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Office of Naval Research or the official policy or position of the Department of Defense or the U.S. government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement>
</funding-group>
<counts><page-count count="10"></page-count>
</counts>
</article-meta>
</front>
</pmc>
</record>
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