A new look at an old virus: patterns of mutation accumulation in the human H1N1 influenza virus since 1918
Identifieur interne : 000204 ( Pmc/Curation ); précédent : 000203; suivant : 000205A new look at an old virus: patterns of mutation accumulation in the human H1N1 influenza virus since 1918
Auteurs : Robert W. Carter [États-Unis] ; John C. Sanford [États-Unis]Source :
- Theoretical Biology & Medical Modelling [ 1742-4682 ] ; 2012.
Abstract
The H1N1 influenza A virus has been circulating in the human population for over 95 years, first manifesting itself in the pandemic of 1917–1918. Initial mortality was extremely high, but dropped exponentially over time. Influenza viruses have high mutation rates, and H1N1 has undergone significant genetic changes since 1918. The exact nature of H1N1 mutation accumulation over time has not been fully explored.
We have made a comprehensive historical analysis of mutational changes within H1N1 by examining over 4100 fully-sequenced H1N1 genomes. This has allowed us to examine the genetic changes arising within H1N1 from 1918 to the present.
We document multiple extinction events, including the previously known extinction of the human H1N1 lineage in the 1950s, and an apparent second extinction of the human H1N1 lineage in 2009. These extinctions appear to be due to a continuous accumulation of mutations. At the time of its disappearance in 2009, the human H1N1 lineage had accumulated over 1400 point mutations (more than 10% of the genome), including approximately 330 non-synonymous changes (7.4% of all codons). The accumulation of both point mutations and non-synonymous amino acid changes occurred at constant rates (μ = 14.4 and 2.4 new mutations/year, respectively), and mutations accumulated uniformly across the entire influenza genome. We observed a continuous erosion over time of codon-specificity in H1N1, including a shift away from host (human, swine, and bird [duck]) codon preference patterns.
While there have been numerous adaptations within the H1N1 genome, most of the genetic changes we document here appear to be non-adaptive, and much of the change appears to be degenerative. We suggest H1N1 has been undergoing natural genetic attenuation, and that significant attenuation may even occur during a single pandemic. This process may play a role in natural pandemic cessation and has apparently contributed to the exponential decline in mortality rates over time, as seen in all major human influenza strains. These findings may be relevant to the development of strategies for managing influenza pandemics and strain evolution.
The online version of this article (doi:10.1186/1742-4682-9-42) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/1742-4682-9-42
PubMed: 23062055
PubMed Central: 3507676
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A new look at an old virus: patterns of mutation accumulation in the human H1N1 influenza virus since 1918</title><author><name sortKey="Carter, Robert W" sort="Carter, Robert W" uniqKey="Carter R" first="Robert W" last="Carter">Robert W. Carter</name><affiliation wicri:level="2"><nlm:aff id="Aff1">FMS Foundation, 877 Marshall Rd, 13165 Waterloo, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>FMS Foundation, 877 Marshall Rd, 13165 Waterloo</wicri:cityArea></affiliation></author><author><name sortKey="Sanford, John C" sort="Sanford, John C" uniqKey="Sanford J" first="John C" last="Sanford">John C. Sanford</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.5386.8</institution-id><institution-id institution-id-type="ISNI">000000041936877X</institution-id><institution>Horticulture Dept, NYSAES,</institution><institution>Cornell University,</institution></institution-wrap>14456 Geneva, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>14456 Geneva</wicri:cityArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23062055</idno><idno type="pmc">3507676</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507676</idno><idno type="RBID">PMC:3507676</idno><idno type="doi">10.1186/1742-4682-9-42</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000204</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000204</idno><idno type="wicri:Area/Pmc/Curation">000204</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000204</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A new look at an old virus: patterns of mutation accumulation in the human H1N1 influenza virus since 1918</title><author><name sortKey="Carter, Robert W" sort="Carter, Robert W" uniqKey="Carter R" first="Robert W" last="Carter">Robert W. Carter</name><affiliation wicri:level="2"><nlm:aff id="Aff1">FMS Foundation, 877 Marshall Rd, 13165 Waterloo, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>FMS Foundation, 877 Marshall Rd, 13165 Waterloo</wicri:cityArea></affiliation></author><author><name sortKey="Sanford, John C" sort="Sanford, John C" uniqKey="Sanford J" first="John C" last="Sanford">John C. Sanford</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.5386.8</institution-id><institution-id institution-id-type="ISNI">000000041936877X</institution-id><institution>Horticulture Dept, NYSAES,</institution><institution>Cornell University,</institution></institution-wrap>14456 Geneva, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>14456 Geneva</wicri:cityArea></affiliation></author></analytic><series><title level="j">Theoretical Biology & Medical Modelling</title><idno type="eISSN">1742-4682</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>The H1N1 influenza A virus has been circulating in the human population for over 95 years, first manifesting itself in the pandemic of 1917–1918. Initial mortality was extremely high, but dropped exponentially over time. Influenza viruses have high mutation rates, and H1N1 has undergone significant genetic changes since 1918. The exact nature of H1N1 mutation accumulation over time has not been fully explored.</p></sec><sec><title>Methods</title><p>We have made a comprehensive historical analysis of mutational changes within H1N1 by examining over 4100 fully-sequenced H1N1 genomes. This has allowed us to examine the genetic changes arising within H1N1 from 1918 to the present.</p></sec><sec><title>Results</title><p>We document multiple extinction events, including the previously known extinction of the human H1N1 lineage in the 1950s, and an apparent second extinction of the human H1N1 lineage in 2009. These extinctions appear to be due to a continuous accumulation of mutations. At the time of its disappearance in 2009, the human H1N1 lineage had accumulated over 1400 point mutations (more than 10% of the genome), including approximately 330 non-synonymous changes (7.4% of all codons). The accumulation of both point mutations and non-synonymous amino acid changes occurred at constant rates (μ = 14.4 and 2.4 new mutations/year, respectively), and mutations accumulated uniformly across the entire influenza genome. We observed a continuous erosion over time of codon-specificity in H1N1, including a shift away from host (human, swine, and bird [duck]) codon preference patterns.</p></sec><sec><title>Conclusions</title><p>While there have been numerous adaptations within the H1N1 genome, most of the genetic changes we document here appear to be non-adaptive, and much of the change appears to be degenerative. We suggest H1N1 has been undergoing natural genetic attenuation, and that significant attenuation may even occur during a single pandemic. This process may play a role in natural pandemic cessation and has apparently contributed to the exponential decline in mortality rates over time, as seen in all major human influenza strains. These findings may be relevant to the development of strategies for managing influenza pandemics and strain evolution.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1186/1742-4682-9-42) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Taubenberger, Jk" uniqKey="Taubenberger J">JK Taubenberger</name></author><author><name sortKey="Morens, Dm" uniqKey="Morens D">DM Morens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simonsen, L" uniqKey="Simonsen L">L Simonsen</name></author><author><name sortKey="Clarke, Mj" uniqKey="Clarke M">MJ Clarke</name></author><author><name sortKey="Schonberger, Lb" uniqKey="Schonberger L">LB Schonberger</name></author><author><name sortKey="Arden, Nh" uniqKey="Arden N">NH Arden</name></author><author><name sortKey="Cox, Nj" 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Jk" uniqKey="Taubenberger J">JK Taubenberger</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Theor Biol Med Model</journal-id><journal-id journal-id-type="iso-abbrev">Theor Biol Med Model</journal-id><journal-title-group><journal-title>Theoretical Biology & Medical Modelling</journal-title></journal-title-group><issn pub-type="epub">1742-4682</issn><publisher><publisher-name>BioMed Central</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23062055</article-id><article-id pub-id-type="pmc">3507676</article-id><article-id pub-id-type="publisher-id">355</article-id><article-id pub-id-type="doi">10.1186/1742-4682-9-42</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research</subject></subj-group></article-categories><title-group><article-title>A new look at an old virus: patterns of mutation accumulation in the human H1N1 influenza virus since 1918</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Carter</surname><given-names>Robert W</given-names></name><address><email>r.carter@fmsfound.org</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Sanford</surname><given-names>John C</given-names></name><address><email>jcs21@cornell.edu</email></address><xref ref-type="aff" rid="Aff2">2</xref></contrib><aff id="Aff1"><label>1</label>FMS Foundation, 877 Marshall Rd, 13165 Waterloo, NY USA</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="GRID">grid.5386.8</institution-id><institution-id institution-id-type="ISNI">000000041936877X</institution-id><institution>Horticulture Dept, NYSAES,</institution><institution>Cornell University,</institution></institution-wrap>14456 Geneva, NY USA</aff></contrib-group><pub-date pub-type="epub"><day>12</day><month>10</month><year>2012</year></pub-date><pub-date pub-type="pmc-release"><day>12</day><month>10</month><year>2012</year></pub-date><pub-date pub-type="collection"><year>2012</year></pub-date><volume>9</volume><elocation-id>42</elocation-id><history><date date-type="received"><day>6</day><month>7</month><year>2012</year></date><date date-type="accepted"><day>4</day><month>10</month><year>2012</year></date></history><permissions><copyright-statement>© Carter and Sanford; licensee BioMed Central Ltd. 2012</copyright-statement><license license-type="OpenAccess"><license-p>This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/2.0">http://creativecommons.org/licenses/by/2.0</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract id="Abs1"><sec><title>Background</title><p>The H1N1 influenza A virus has been circulating in the human population for over 95 years, first manifesting itself in the pandemic of 1917–1918. Initial mortality was extremely high, but dropped exponentially over time. Influenza viruses have high mutation rates, and H1N1 has undergone significant genetic changes since 1918. The exact nature of H1N1 mutation accumulation over time has not been fully explored.</p></sec><sec><title>Methods</title><p>We have made a comprehensive historical analysis of mutational changes within H1N1 by examining over 4100 fully-sequenced H1N1 genomes. This has allowed us to examine the genetic changes arising within H1N1 from 1918 to the present.</p></sec><sec><title>Results</title><p>We document multiple extinction events, including the previously known extinction of the human H1N1 lineage in the 1950s, and an apparent second extinction of the human H1N1 lineage in 2009. These extinctions appear to be due to a continuous accumulation of mutations. At the time of its disappearance in 2009, the human H1N1 lineage had accumulated over 1400 point mutations (more than 10% of the genome), including approximately 330 non-synonymous changes (7.4% of all codons). The accumulation of both point mutations and non-synonymous amino acid changes occurred at constant rates (μ = 14.4 and 2.4 new mutations/year, respectively), and mutations accumulated uniformly across the entire influenza genome. We observed a continuous erosion over time of codon-specificity in H1N1, including a shift away from host (human, swine, and bird [duck]) codon preference patterns.</p></sec><sec><title>Conclusions</title><p>While there have been numerous adaptations within the H1N1 genome, most of the genetic changes we document here appear to be non-adaptive, and much of the change appears to be degenerative. We suggest H1N1 has been undergoing natural genetic attenuation, and that significant attenuation may even occur during a single pandemic. This process may play a role in natural pandemic cessation and has apparently contributed to the exponential decline in mortality rates over time, as seen in all major human influenza strains. These findings may be relevant to the development of strategies for managing influenza pandemics and strain evolution.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1186/1742-4682-9-42) contains supplementary material, which is available to authorized users.</p></sec></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd>Influenza</kwd><kwd>H1N1</kwd><kwd>Swine flu</kwd><kwd>Mutation accumulation</kwd><kwd>Pandemic</kwd><kwd>Evolution</kwd><kwd>Error catastrophe</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2012</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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