Genetic Compatibility and Virulence of Reassortants Derived from Contemporary Avian H5N1 and Human H3N2 Influenza A Viruses
Identifieur interne : 000B98 ( Pmc/Curation ); précédent : 000B97; suivant : 000B99Genetic Compatibility and Virulence of Reassortants Derived from Contemporary Avian H5N1 and Human H3N2 Influenza A Viruses
Auteurs : Li-Mei Chen ; C. Todd Davis ; Hong Zhou ; Nancy J. Cox ; Ruben O. DonisSource :
- PLoS Pathogens [ 1553-7366 ] ; 2008.
Abstract
The segmented structure of the influenza virus genome plays a pivotal role in its adaptation to new hosts and the emergence of pandemics. Despite concerns about the pandemic threat posed by highly pathogenic avian influenza H5N1 viruses, little is known about the biological properties of H5N1 viruses that may emerge following reassortment with contemporary human influenza viruses. In this study, we used reverse genetics to generate the 63 possible virus reassortants derived from H5N1 and H3N2 viruses, containing the H5N1 surface protein genes, and analyzed their viability, replication efficiency, and mouse virulence. Specific constellations of avian–human viral genes proved deleterious for viral replication in cell culture, possibly due to disruption of molecular interaction networks. In particular, striking phenotypes were noted with heterologous polymerase subunits, as well as NP and M, or NS. However, nearly one-half of the reassortants replicated with high efficiency
Url:
DOI: 10.1371/journal.ppat.1000072
PubMed: 18497857
PubMed Central: 2374906
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genetic Compatibility and Virulence of Reassortants Derived from Contemporary Avian H5N1 and Human H3N2 Influenza A Viruses</title><author><name sortKey="Chen, Li Mei" sort="Chen, Li Mei" uniqKey="Chen L" first="Li-Mei" last="Chen">Li-Mei Chen</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Davis, C Todd" sort="Davis, C Todd" uniqKey="Davis C" first="C. Todd" last="Davis">C. Todd Davis</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Zhou, Hong" sort="Zhou, Hong" uniqKey="Zhou H" first="Hong" last="Zhou">Hong Zhou</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Cox, Nancy J" sort="Cox, Nancy J" uniqKey="Cox N" first="Nancy J." last="Cox">Nancy J. Cox</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Donis, Ruben O" sort="Donis, Ruben O" uniqKey="Donis R" first="Ruben O." last="Donis">Ruben O. Donis</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">18497857</idno><idno type="pmc">2374906</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374906</idno><idno type="RBID">PMC:2374906</idno><idno type="doi">10.1371/journal.ppat.1000072</idno><date when="2008">2008</date><idno type="wicri:Area/Pmc/Corpus">000B98</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000B98</idno><idno type="wicri:Area/Pmc/Curation">000B98</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000B98</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genetic Compatibility and Virulence of Reassortants Derived from Contemporary Avian H5N1 and Human H3N2 Influenza A Viruses</title><author><name sortKey="Chen, Li Mei" sort="Chen, Li Mei" uniqKey="Chen L" first="Li-Mei" last="Chen">Li-Mei Chen</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Davis, C Todd" sort="Davis, C Todd" uniqKey="Davis C" first="C. Todd" last="Davis">C. Todd Davis</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Zhou, Hong" sort="Zhou, Hong" uniqKey="Zhou H" first="Hong" last="Zhou">Hong Zhou</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Cox, Nancy J" sort="Cox, Nancy J" uniqKey="Cox N" first="Nancy J." last="Cox">Nancy J. Cox</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Donis, Ruben O" sort="Donis, Ruben O" uniqKey="Donis R" first="Ruben O." last="Donis">Ruben O. Donis</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">PLoS Pathogens</title><idno type="ISSN">1553-7366</idno><idno type="eISSN">1553-7374</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The segmented structure of the influenza virus genome plays a pivotal role in its adaptation to new hosts and the emergence of pandemics. Despite concerns about the pandemic threat posed by highly pathogenic avian influenza H5N1 viruses, little is known about the biological properties of H5N1 viruses that may emerge following reassortment with contemporary human influenza viruses. In this study, we used reverse genetics to generate the 63 possible virus reassortants derived from H5N1 and H3N2 viruses, containing the H5N1 surface protein genes, and analyzed their viability, replication efficiency, and mouse virulence. Specific constellations of avian–human viral genes proved deleterious for viral replication in cell culture, possibly due to disruption of molecular interaction networks. In particular, striking phenotypes were noted with heterologous polymerase subunits, as well as NP and M, or NS. However, nearly one-half of the reassortants replicated with high efficiency <italic>in vitro</italic>, revealing a high degree of compatibility between avian and human virus genes. Thirteen reassortants displayed virulent phenotypes in mice and may pose the greatest threat for mammalian hosts. Interestingly, one of the most pathogenic reassortants contained avian PB1, resembling the 1957 and 1968 pandemic viruses. Our results reveal the broad spectrum of phenotypes associated with H5N1/H3N2 reassortment and a possible role for the avian PB1 in the emergence of pandemic influenza. These observations have important implications for risk assessment of H5N1 reassortant viruses detected in surveillance programs.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Taubenberger, Jk" uniqKey="Taubenberger J">JK Taubenberger</name></author><author><name sortKey="Reid, Ah" uniqKey="Reid A">AH Reid</name></author><author><name sortKey="Lourens, Rm" uniqKey="Lourens R">RM Lourens</name></author><author><name sortKey="Wang, R" uniqKey="Wang R">R Wang</name></author><author><name sortKey="Jin, G" uniqKey="Jin G">G Jin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reid, Ah" uniqKey="Reid A">AH Reid</name></author><author><name sortKey="Taubenberger, Jk" uniqKey="Taubenberger J">JK Taubenberger</name></author><author><name sortKey="Fanning, Tg" uniqKey="Fanning T">TG Fanning</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kawaoka, Y" uniqKey="Kawaoka 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Pathog</journal-id><journal-id journal-id-type="iso-abbrev">PLoS Pathog</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plospath</journal-id><journal-title-group><journal-title>PLoS Pathogens</journal-title></journal-title-group><issn pub-type="ppub">1553-7366</issn><issn pub-type="epub">1553-7374</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">18497857</article-id><article-id pub-id-type="pmc">2374906</article-id><article-id pub-id-type="publisher-id">08-PLPA-RA-0168R2</article-id><article-id pub-id-type="doi">10.1371/journal.ppat.1000072</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline"><subject>Virology/Animal Models of Infection</subject><subject>Virology/Emerging Viral Diseases</subject><subject>Virology/Virus Evolution and Symbiosis</subject></subj-group></article-categories><title-group><article-title>Genetic Compatibility and Virulence of Reassortants Derived from Contemporary Avian H5N1 and Human H3N2 Influenza A Viruses</article-title><alt-title alt-title-type="running-head">H5N1 Reassortant Influenza Viruses</alt-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Chen</surname><given-names>Li-Mei</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Davis</surname><given-names>C. Todd</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Zhou</surname><given-names>Hong</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Cox</surname><given-names>Nancy J.</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Donis</surname><given-names>Ruben O.</given-names></name><xref ref-type="aff" rid="aff1"></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><addr-line>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Garcia-Sastre</surname><given-names>Adolfo</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1">Mount Sinai School of Medicine, United States of America</aff><author-notes><corresp id="cor1">* E-mail: <email>rvd6@cdc.gov</email></corresp><fn fn-type="con"><p>Conceived and designed the experiments: LC CD NC RD. Performed the experiments: LC CD. Analyzed the data: LC CD HZ RD. Contributed reagents/materials/analysis tools: LC. Wrote the paper: LC CD HZ RD.</p></fn></author-notes><pub-date pub-type="collection"><month>5</month><year>2008</year></pub-date><pub-date pub-type="epub"><day>23</day><month>5</month><year>2008</year></pub-date><volume>4</volume><issue>5</issue><elocation-id>e1000072</elocation-id><history><date date-type="received"><day>21</day><month>2</month><year>2008</year></date><date date-type="accepted"><day>15</day><month>4</month><year>2008</year></date></history><permissions><copyright-statement>This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.</copyright-statement><copyright-year>2008</copyright-year><license xlink:href="https://creativecommons.org/publicdomain/zero/1.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.</license-p></license></permissions><abstract><p>The segmented structure of the influenza virus genome plays a pivotal role in its adaptation to new hosts and the emergence of pandemics. Despite concerns about the pandemic threat posed by highly pathogenic avian influenza H5N1 viruses, little is known about the biological properties of H5N1 viruses that may emerge following reassortment with contemporary human influenza viruses. In this study, we used reverse genetics to generate the 63 possible virus reassortants derived from H5N1 and H3N2 viruses, containing the H5N1 surface protein genes, and analyzed their viability, replication efficiency, and mouse virulence. Specific constellations of avian–human viral genes proved deleterious for viral replication in cell culture, possibly due to disruption of molecular interaction networks. In particular, striking phenotypes were noted with heterologous polymerase subunits, as well as NP and M, or NS. However, nearly one-half of the reassortants replicated with high efficiency <italic>in vitro</italic>, revealing a high degree of compatibility between avian and human virus genes. Thirteen reassortants displayed virulent phenotypes in mice and may pose the greatest threat for mammalian hosts. Interestingly, one of the most pathogenic reassortants contained avian PB1, resembling the 1957 and 1968 pandemic viruses. Our results reveal the broad spectrum of phenotypes associated with H5N1/H3N2 reassortment and a possible role for the avian PB1 in the emergence of pandemic influenza. These observations have important implications for risk assessment of H5N1 reassortant viruses detected in surveillance programs.</p></abstract><abstract abstract-type="summary"><title>Author Summary</title><p>The influenza pandemics of 1957 and 1968 were caused by hybrid viruses consisting of a mixture of human and avian influenza genes. The introduction of avian genes resulted in a sudden change of the virus surface antigens, allowing its worldwide spread due to lack of immunity in the population. The highly pathogenic avian influenza H5N1 virus has continued its spread in domestic and wild birds in Asia, Europe, and Africa. Although H5N1 infection in humans is rare and person-to-person transmission is very inefficient, the steady accumulation of human cases has raised concern over the possible reassortment between H5N1 and human seasonal influenza resulting in a virus with new surface antigens and pandemic potential. In this study, we used recombinant DNA technology to generate a systematic collection of hybrid viruses (with genes from human and avian viruses) bearing H5N1 surface antigens and analyzed their properties in cell culture and in mice. The H5N1 hybrid viruses revealed a broad range of viability and multiplication capacity in cell cultures. In addition, several H5N1 hybrid viruses were highly virulent in mice. Results from this systematic analysis provide important insight to support risk assessment of reassortant H5N1 avian influenza viruses.</p></abstract><counts><page-count count="11"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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