Virulence Determinants of Pandemic A(H1N1)2009 Influenza Virus in a Mouse Model
Identifieur interne : 000509 ( Pmc/Checkpoint ); précédent : 000508; suivant : 000510Virulence Determinants of Pandemic A(H1N1)2009 Influenza Virus in a Mouse Model
Auteurs : Ryuta Uraki [Japon] ; Maki Kiso [Japon] ; Kyoko Shinya [Japon] ; Hideo Goto [Japon] ; Ryo Takano [Japon] ; Kiyoko Iwatsuki-Horimoto [Japon] ; Kazuo Takahashi [Japon] ; Rod S. Daniels [Royaume-Uni] ; Olav Hungnes [Norvège] ; Tokiko Watanabe [Japon, États-Unis] ; Yoshihiro Kawaoka [Japon, États-Unis]Source :
- Journal of Virology [ 0022-538X ] ; 2013.
Abstract
A novel swine-origin H1N1 influenza virus [A(H1N1)pdm09 virus] caused the 2009 influenza pandemic. Most patients exhibited mild symptoms similar to seasonal influenza, but some experienced severe clinical signs and, in the worst cases, died. Such differences in symptoms are generally associated with preexisting medical conditions, but recent reports indicate the possible involvement of viral factors in clinical severity. To better understand the mechanism of pathogenicity of the A(H1N1)pdm09 virus, here, we compared five viruses that are genetically similar but were isolated from patients with either severe or mild symptoms. In a mouse model, A/Norway/3487/2009 (Norway3487) virus exhibited greater pathogenicity than did A/Osaka/164/2009 (Osaka164) virus. By exploiting reassortant viruses between these two viruses, we found that viruses possessing the hemagglutinin (HA) gene of Norway3487 in the genetic background of Osaka164 were more pathogenic in mice than other reassortant viruses, indicating a role for HA in the high virulence of Norway3487 virus. Intriguingly, a virus possessing HA, NA, and NS derived from Norway3487 exhibited greater pathogenicity in mice in concert with PB2 and PB1 derived from Osaka164 than did the parental Norway3487 virus. These findings demonstrate that reassortment between A(H1N1)pdm09 viruses can lead to increased pathogenicity and highlight the need for continued surveillance of A(H1N1)pdm09 viruses.
Url:
DOI: 10.1128/JVI.01565-12
PubMed: 23221570
PubMed Central: 3571452
Affiliations:
- Japon, Norvège, Royaume-Uni, États-Unis
- Angleterre, Grand Londres, Région de Kantō, Wisconsin, Østlandet
- Londres, Madison (Wisconsin), Oslo, Tokyo
- Université de Tokyo, Université du Wisconsin à Madison
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nuts="2">Østlandet</region></placeName></affiliation></author><author><name sortKey="Watanabe, Tokiko" sort="Watanabe, Tokiko" uniqKey="Watanabe T" first="Tokiko" last="Watanabe">Tokiko Watanabe</name><affiliation wicri:level="1"><nlm:aff id="aff6">ERATO Infection-Induced Host Responses Project (JST), Saitama, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>ERATO Infection-Induced Host Responses Project (JST), Saitama</wicri:regionArea><wicri:noRegion>Saitama</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff7">Department of Pathobiological Sciences, University of Wisconsin—Madison, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathobiological Sciences, University of Wisconsin—Madison, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region><settlement type="city">Madison (Wisconsin)</settlement></placeName><orgName type="university">Université du Wisconsin à Madison</orgName></affiliation></author><author><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><affiliation wicri:level="4"><nlm:aff id="aff1">Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName><orgName type="university" n="3">Université du Wisconsin à Madison</orgName></affiliation><affiliation wicri:level="1"><nlm:aff 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sort="Uraki, Ryuta" uniqKey="Uraki R" first="Ryuta" last="Uraki">Ryuta Uraki</name><affiliation wicri:level="4"><nlm:aff id="aff1">Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Kiso, Maki" sort="Kiso, Maki" uniqKey="Kiso M" first="Maki" last="Kiso">Maki Kiso</name><affiliation wicri:level="4"><nlm:aff id="aff1">Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Shinya, Kyoko" sort="Shinya, Kyoko" uniqKey="Shinya K" first="Kyoko" last="Shinya">Kyoko Shinya</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Microbiology and Infectious Diseases, Kobe University, Hyogo, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Microbiology and Infectious Diseases, Kobe University, Hyogo</wicri:regionArea><wicri:noRegion>Hyogo</wicri:noRegion></affiliation></author><author><name sortKey="Goto, Hideo" sort="Goto, Hideo" uniqKey="Goto H" first="Hideo" last="Goto">Hideo Goto</name><affiliation wicri:level="4"><nlm:aff id="aff1">Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Takano, Ryo" sort="Takano, Ryo" uniqKey="Takano R" first="Ryo" last="Takano">Ryo Takano</name><affiliation wicri:level="4"><nlm:aff id="aff1">Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Iwatsuki Horimoto, Kiyoko" sort="Iwatsuki Horimoto, Kiyoko" uniqKey="Iwatsuki Horimoto K" first="Kiyoko" last="Iwatsuki-Horimoto">Kiyoko Iwatsuki-Horimoto</name><affiliation wicri:level="4"><nlm:aff id="aff1">Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Takahashi, Kazuo" sort="Takahashi, Kazuo" uniqKey="Takahashi K" first="Kazuo" last="Takahashi">Kazuo Takahashi</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Infectious Diseases, Osaka Prefectural Institute of Public Health, Osaka, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Infectious Diseases, Osaka Prefectural Institute of Public Health, Osaka</wicri:regionArea><wicri:noRegion>Osaka</wicri:noRegion></affiliation></author><author><name sortKey="Daniels, Rod S" sort="Daniels, Rod S" uniqKey="Daniels R" first="Rod S." last="Daniels">Rod S. Daniels</name><affiliation wicri:level="3"><nlm:aff id="aff4">Virology Division, MRC-National Institute for Medical Research, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Virology Division, MRC-National Institute for Medical Research, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Hungnes, Olav" sort="Hungnes, Olav" uniqKey="Hungnes O" first="Olav" last="Hungnes">Olav Hungnes</name><affiliation wicri:level="3"><nlm:aff id="aff5">Department of Virology, Norwegian Institute of Public Health, Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Department of Virology, Norwegian Institute of Public Health, Oslo</wicri:regionArea><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName></affiliation></author><author><name sortKey="Watanabe, Tokiko" sort="Watanabe, Tokiko" uniqKey="Watanabe T" first="Tokiko" last="Watanabe">Tokiko Watanabe</name><affiliation wicri:level="1"><nlm:aff id="aff6">ERATO Infection-Induced Host Responses Project (JST), Saitama, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>ERATO Infection-Induced Host Responses Project (JST), Saitama</wicri:regionArea><wicri:noRegion>Saitama</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff7">Department of Pathobiological Sciences, University of Wisconsin—Madison, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathobiological Sciences, University of Wisconsin—Madison, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region><settlement type="city">Madison (Wisconsin)</settlement></placeName><orgName type="university">Université du Wisconsin à Madison</orgName></affiliation></author><author><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><affiliation wicri:level="4"><nlm:aff id="aff1">Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName><orgName type="university" n="3">Université du Wisconsin à Madison</orgName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6">ERATO Infection-Induced Host Responses Project (JST), Saitama, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>ERATO Infection-Induced Host Responses Project (JST), Saitama</wicri:regionArea><wicri:noRegion>Saitama</wicri:noRegion><placeName><settlement type="city">Tokyo</settlement><region type="province">Région de Kantō</region></placeName><orgName type="university" n="3">Université de Tokyo</orgName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff7">Department of Pathobiological Sciences, University of Wisconsin—Madison, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathobiological Sciences, University of Wisconsin—Madison, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region><settlement type="city">Madison (Wisconsin)</settlement></placeName><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName><orgName type="university" n="3">Université du Wisconsin à Madison</orgName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff8">Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName><orgName type="university" n="3">Université du Wisconsin à Madison</orgName></affiliation></author></analytic><series><title level="j">Journal of Virology</title><idno type="ISSN">0022-538X</idno><idno type="eISSN">1098-5514</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>A novel swine-origin H1N1 influenza virus [A(H1N1)pdm09 virus] caused the 2009 influenza pandemic. Most patients exhibited mild symptoms similar to seasonal influenza, but some experienced severe clinical signs and, in the worst cases, died. Such differences in symptoms are generally associated with preexisting medical conditions, but recent reports indicate the possible involvement of viral factors in clinical severity. To better understand the mechanism of pathogenicity of the A(H1N1)pdm09 virus, here, we compared five viruses that are genetically similar but were isolated from patients with either severe or mild symptoms. In a mouse model, A/Norway/3487/2009 (Norway3487) virus exhibited greater pathogenicity than did A/Osaka/164/2009 (Osaka164) virus. By exploiting reassortant viruses between these two viruses, we found that viruses possessing the hemagglutinin (HA) gene of Norway3487 in the genetic background of Osaka164 were more pathogenic in mice than other reassortant viruses, indicating a role for HA in the high virulence of Norway3487 virus. Intriguingly, a virus possessing HA, NA, and NS derived from Norway3487 exhibited greater pathogenicity in mice in concert with PB2 and PB1 derived from Osaka164 than did the parental Norway3487 virus. These findings demonstrate that reassortment between A(H1N1)pdm09 viruses can lead to increased pathogenicity and highlight the need for continued surveillance of A(H1N1)pdm09 viruses.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Virol</journal-id><journal-id journal-id-type="iso-abbrev">J. Virol</journal-id><journal-id journal-id-type="hwp">jvi</journal-id><journal-id journal-id-type="pmc">jvi</journal-id><journal-id journal-id-type="publisher-id">JVI</journal-id><journal-title-group><journal-title>Journal of Virology</journal-title></journal-title-group><issn pub-type="ppub">0022-538X</issn><issn pub-type="epub">1098-5514</issn><publisher><publisher-name>American Society for Microbiology</publisher-name><publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23221570</article-id><article-id pub-id-type="pmc">3571452</article-id><article-id pub-id-type="publisher-id">01565-12</article-id><article-id pub-id-type="doi">10.1128/JVI.01565-12</article-id><article-categories><subj-group subj-group-type="heading"><subject>Pathogenesis and Immunity</subject></subj-group></article-categories><title-group><article-title>Virulence Determinants of Pandemic A(H1N1)2009 Influenza Virus in a Mouse Model</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Uraki</surname><given-names>Ryuta</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kiso</surname><given-names>Maki</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Shinya</surname><given-names>Kyoko</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Goto</surname><given-names>Hideo</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Takano</surname><given-names>Ryo</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Iwatsuki-Horimoto</surname><given-names>Kiyoko</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Takahashi</surname><given-names>Kazuo</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Daniels</surname><given-names>Rod S.</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hungnes</surname><given-names>Olav</given-names></name><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Watanabe</surname><given-names>Tokiko</given-names></name><xref ref-type="aff" rid="aff6"><sup>f</sup></xref><xref ref-type="aff" rid="aff7"><sup>g</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Kawaoka</surname><given-names>Yoshihiro</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff6"><sup>f</sup></xref><xref ref-type="aff" rid="aff7"><sup>g</sup></xref><xref ref-type="aff" rid="aff8"><sup>h</sup></xref></contrib><aff id="aff1"><label>a</label>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan</aff><aff id="aff2"><label>b</label>Department of Microbiology and Infectious Diseases, Kobe University, Hyogo, Japan</aff><aff id="aff3"><label>c</label>Department of Infectious Diseases, Osaka Prefectural Institute of Public Health, Osaka, Japan</aff><aff id="aff4"><label>d</label>Virology Division, MRC-National Institute for Medical Research, London, United Kingdom</aff><aff id="aff5"><label>e</label>Department of Virology, Norwegian Institute of Public Health, Oslo, Norway</aff><aff id="aff6"><label>f</label>ERATO Infection-Induced Host Responses Project (JST), Saitama, Japan</aff><aff id="aff7"><label>g</label>Department of Pathobiological Sciences, University of Wisconsin—Madison, Madison, Wisconsin, USA</aff><aff id="aff8"><label>h</label>Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan</aff></contrib-group><author-notes><corresp>Address correspondence to Tokiko Watanabe, <email>twatanabe@svm.vetmed.wisc.edu</email>, or Yoshihiro Kawaoka, <email>kawaoka@ims.u-tokyo.ac.jp</email>.</corresp></author-notes><pub-date pub-type="ppub"><month>2</month><year>2013</year></pub-date><volume>87</volume><issue>4</issue><fpage>2226</fpage><lpage>2233</lpage><history><date date-type="received"><day>20</day><month>6</month><year>2012</year></date><date date-type="accepted"><day>30</day><month>11</month><year>2012</year></date></history><permissions><copyright-statement>Copyright © 2013, American Society for Microbiology. All Rights Reserved.</copyright-statement><copyright-year>2013</copyright-year><copyright-holder>American Society for Microbiology</copyright-holder></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zjv00413002226.pdf"></self-uri><abstract><p>A novel swine-origin H1N1 influenza virus [A(H1N1)pdm09 virus] caused the 2009 influenza pandemic. Most patients exhibited mild symptoms similar to seasonal influenza, but some experienced severe clinical signs and, in the worst cases, died. Such differences in symptoms are generally associated with preexisting medical conditions, but recent reports indicate the possible involvement of viral factors in clinical severity. To better understand the mechanism of pathogenicity of the A(H1N1)pdm09 virus, here, we compared five viruses that are genetically similar but were isolated from patients with either severe or mild symptoms. In a mouse model, A/Norway/3487/2009 (Norway3487) virus exhibited greater pathogenicity than did A/Osaka/164/2009 (Osaka164) virus. By exploiting reassortant viruses between these two viruses, we found that viruses possessing the hemagglutinin (HA) gene of Norway3487 in the genetic background of Osaka164 were more pathogenic in mice than other reassortant viruses, indicating a role for HA in the high virulence of Norway3487 virus. Intriguingly, a virus possessing HA, NA, and NS derived from Norway3487 exhibited greater pathogenicity in mice in concert with PB2 and PB1 derived from Osaka164 than did the parental Norway3487 virus. These findings demonstrate that reassortment between A(H1N1)pdm09 viruses can lead to increased pathogenicity and highlight the need for continued surveillance of A(H1N1)pdm09 viruses.</p></abstract></article-meta></front></pmc><affiliations><list><country><li>Japon</li><li>Norvège</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Grand Londres</li><li>Région de Kantō</li><li>Wisconsin</li><li>Østlandet</li></region><settlement><li>Londres</li><li>Madison (Wisconsin)</li><li>Oslo</li><li>Tokyo</li></settlement><orgName><li>Université de Tokyo</li><li>Université du Wisconsin à Madison</li></orgName></list><tree><country name="Japon"><region name="Région de Kantō"><name sortKey="Uraki, Ryuta" sort="Uraki, Ryuta" uniqKey="Uraki R" first="Ryuta" last="Uraki">Ryuta Uraki</name></region><name sortKey="Goto, Hideo" sort="Goto, Hideo" uniqKey="Goto H" first="Hideo" last="Goto">Hideo Goto</name><name sortKey="Iwatsuki Horimoto, Kiyoko" sort="Iwatsuki Horimoto, Kiyoko" uniqKey="Iwatsuki Horimoto K" first="Kiyoko" last="Iwatsuki-Horimoto">Kiyoko Iwatsuki-Horimoto</name><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><name sortKey="Kiso, Maki" sort="Kiso, Maki" uniqKey="Kiso M" first="Maki" last="Kiso">Maki Kiso</name><name sortKey="Shinya, Kyoko" sort="Shinya, Kyoko" uniqKey="Shinya K" first="Kyoko" last="Shinya">Kyoko Shinya</name><name sortKey="Takahashi, Kazuo" sort="Takahashi, Kazuo" uniqKey="Takahashi K" first="Kazuo" last="Takahashi">Kazuo Takahashi</name><name sortKey="Takano, Ryo" sort="Takano, Ryo" uniqKey="Takano R" first="Ryo" last="Takano">Ryo Takano</name><name sortKey="Watanabe, Tokiko" sort="Watanabe, Tokiko" uniqKey="Watanabe T" first="Tokiko" last="Watanabe">Tokiko Watanabe</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Daniels, Rod S" sort="Daniels, Rod S" uniqKey="Daniels R" first="Rod S." last="Daniels">Rod S. Daniels</name></region></country><country name="Norvège"><region name="Østlandet"><name sortKey="Hungnes, Olav" sort="Hungnes, Olav" uniqKey="Hungnes O" first="Olav" last="Hungnes">Olav Hungnes</name></region></country><country name="États-Unis"><region name="Wisconsin"><name sortKey="Watanabe, Tokiko" sort="Watanabe, Tokiko" uniqKey="Watanabe T" first="Tokiko" last="Watanabe">Tokiko Watanabe</name></region><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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