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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Reassortment between avian H5N1 and human H3N2 influenza viruses creates hybrid viruses with substantial virulence</title><author><name sortKey="Li, Chengjun" sort="Li, Chengjun" uniqKey="Li C" first="Chengjun" last="Li">Chengjun Li</name><affiliation><nlm:aff id="aff1">Influenza Research Institute, School of Veterinary Medicine,<institution>University of Wisconsin-Madison</institution>, Madison, WI 53711;</nlm:aff></affiliation></author><author><name sortKey="Hatta, Masato" sort="Hatta, Masato" uniqKey="Hatta M" first="Masato" last="Hatta">Masato Hatta</name><affiliation><nlm:aff id="aff1">Influenza Research Institute, School of Veterinary Medicine,<institution>University of Wisconsin-Madison</institution>, Madison, WI 53711;</nlm:aff></affiliation></author><author><name sortKey="Nidom, Chairul A" sort="Nidom, Chairul A" uniqKey="Nidom C" first="Chairul A." last="Nidom">Chairul A. Nidom</name><affiliation><nlm:aff wicri:cut=" and" id="aff2">Faculty of Veterinary Medicine</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Collaborating Research Center-Emerging and Reemerging Infectious Diseases, Tropical Disease Centre,<institution>Airlangga University</institution>, Surabaya 60115,<country>Indonesia</country>;</nlm:aff></affiliation></author><author><name sortKey="Muramoto, Yukiko" sort="Muramoto, Yukiko" uniqKey="Muramoto Y" first="Yukiko" last="Muramoto">Yukiko Muramoto</name><affiliation><nlm:aff wicri:cut=" and" id="aff4">Division of Virology, Department of Microbiology and Immunology</nlm:aff></affiliation></author><author><name sortKey="Watanabe, Shinji" sort="Watanabe, Shinji" uniqKey="Watanabe S" first="Shinji" last="Watanabe">Shinji Watanabe</name><affiliation><nlm:aff id="aff1">Influenza Research Institute, School of Veterinary Medicine,<institution>University of Wisconsin-Madison</institution>, Madison, WI 53711;</nlm:aff></affiliation></author><author><name sortKey="Neumann, Gabriele" sort="Neumann, Gabriele" uniqKey="Neumann G" first="Gabriele" last="Neumann">Gabriele Neumann</name><affiliation><nlm:aff id="aff1">Influenza Research Institute, School of Veterinary Medicine,<institution>University of Wisconsin-Madison</institution>, Madison, WI 53711;</nlm:aff></affiliation></author><author><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><affiliation><nlm:aff id="aff1">Influenza Research Institute, School of Veterinary Medicine,<institution>University of Wisconsin-Madison</institution>, Madison, WI 53711;</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="aff4">Division of Virology, Department of Microbiology and Immunology</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff5">International Research Center for Infectious Diseases, Institute of Medical Science,<institution>University of Tokyo</institution>, Tokyo 108-8639,<country>Japan</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff6">Infection-Induced Host Responses Project,<institution>Exploratory Research for Advanced Technology</institution>, Saitama 332-0012,<country>Japan</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20176961</idno><idno type="pmc">2842136</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842136</idno><idno type="RBID">PMC:2842136</idno><idno type="doi">10.1073/pnas.0912807107</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000749</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000749</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Reassortment between avian H5N1 and human H3N2 influenza viruses creates hybrid viruses with substantial virulence</title><author><name sortKey="Li, Chengjun" sort="Li, Chengjun" uniqKey="Li C" first="Chengjun" last="Li">Chengjun Li</name><affiliation><nlm:aff id="aff1">Influenza Research Institute, School of Veterinary Medicine,<institution>University of Wisconsin-Madison</institution>, Madison, WI 53711;</nlm:aff></affiliation></author><author><name sortKey="Hatta, Masato" sort="Hatta, Masato" uniqKey="Hatta M" first="Masato" last="Hatta">Masato Hatta</name><affiliation><nlm:aff id="aff1">Influenza Research Institute, School of Veterinary Medicine,<institution>University of Wisconsin-Madison</institution>, Madison, WI 53711;</nlm:aff></affiliation></author><author><name sortKey="Nidom, Chairul A" sort="Nidom, Chairul A" uniqKey="Nidom C" first="Chairul A." last="Nidom">Chairul A. Nidom</name><affiliation><nlm:aff wicri:cut=" and" id="aff2">Faculty of Veterinary Medicine</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Collaborating Research Center-Emerging and Reemerging Infectious Diseases, Tropical Disease Centre,<institution>Airlangga University</institution>, Surabaya 60115,<country>Indonesia</country>;</nlm:aff></affiliation></author><author><name sortKey="Muramoto, Yukiko" sort="Muramoto, Yukiko" uniqKey="Muramoto Y" first="Yukiko" last="Muramoto">Yukiko Muramoto</name><affiliation><nlm:aff wicri:cut=" and" id="aff4">Division of Virology, Department of Microbiology and Immunology</nlm:aff></affiliation></author><author><name sortKey="Watanabe, Shinji" sort="Watanabe, Shinji" uniqKey="Watanabe S" first="Shinji" last="Watanabe">Shinji Watanabe</name><affiliation><nlm:aff id="aff1">Influenza Research Institute, School of Veterinary Medicine,<institution>University of Wisconsin-Madison</institution>, Madison, WI 53711;</nlm:aff></affiliation></author><author><name sortKey="Neumann, Gabriele" sort="Neumann, Gabriele" uniqKey="Neumann G" first="Gabriele" last="Neumann">Gabriele Neumann</name><affiliation><nlm:aff id="aff1">Influenza Research Institute, School of Veterinary Medicine,<institution>University of Wisconsin-Madison</institution>, Madison, WI 53711;</nlm:aff></affiliation></author><author><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><affiliation><nlm:aff id="aff1">Influenza Research Institute, School of Veterinary Medicine,<institution>University of Wisconsin-Madison</institution>, Madison, WI 53711;</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="aff4">Division of Virology, Department of Microbiology and Immunology</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff5">International Research Center for Infectious Diseases, Institute of Medical Science,<institution>University of Tokyo</institution>, Tokyo 108-8639,<country>Japan</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff6">Infection-Induced Host Responses Project,<institution>Exploratory Research for Advanced Technology</institution>, Saitama 332-0012,<country>Japan</country></nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The spread of avian H5N1 influenza viruses around the globe has become a worldwide public health concern. To evaluate the pathogenic potential of reassortant viruses between currently cocirculating avian H5N1 and human H3N2 influenza viruses, we generated all the 254 combinations of reassortant viruses between A/chicken/South Kalimantan/UT6028/06 (SK06, H5N1) and A/Tokyo/Ut-Sk-1/07 (Tok07, H3N2) influenza viruses by reverse genetics. We found that the presence of Tok07 PB2 protein in the ribonucleoprotein (RNP) complex allowed efficient viral RNA transcription in a minigenome assay and that RNP activity played an essential role in the viability and replicative ability of the reassortant viruses. When the pathogenicity of 75 reassortant H5 viruses was tested in mice, 22 were more pathogenic than the parental SK06 virus, and three were extremely virulent. Strikingly, all 22 of these viruses obtained their <italic>PB2</italic> segment from Tok07 virus. Further analysis showed that Tok07 <italic>PB1</italic> alone lacked the ability to enhance the pathogenicity of the reassortant viruses but could do so by cooperating with Tok07 <italic>PB2</italic>. Our data demonstrate that reassortment between an avian H5N1 virus with low pathogenicity in mice and a human virus could result in highly pathogenic viruses and that the human virus <italic>PB2</italic> segment functions in the background of an avian H5N1 virus, enhancing its virulence. Our findings highlight the importance of surveillance programs to monitor the emergence of human H5 reassortant viruses, especially those containing a <italic>PB2</italic> segment of human origin.</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">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="hwp">pnas</journal-id><journal-id journal-id-type="pmc">pnas</journal-id><journal-id journal-id-type="publisher-id">PNAS</journal-id><journal-title-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title></journal-title-group><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">20176961</article-id><article-id pub-id-type="pmc">2842136</article-id><article-id pub-id-type="publisher-id">200912807</article-id><article-id pub-id-type="doi">10.1073/pnas.0912807107</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Microbiology</subject></subj-group></subj-group></article-categories><title-group><article-title>Reassortment between avian H5N1 and human H3N2 influenza viruses creates hybrid viruses with substantial virulence</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Li</surname><given-names>Chengjun</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hatta</surname><given-names>Masato</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nidom</surname><given-names>Chairul A.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Muramoto</surname><given-names>Yukiko</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Watanabe</surname><given-names>Shinji</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Neumann</surname><given-names>Gabriele</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><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="aff4"><sup>d</sup></xref><xref ref-type="aff" rid="aff5"><sup>e</sup></xref><xref ref-type="aff" rid="aff6"><sup>f</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><aff id="aff1"><sup>a</sup>Influenza Research Institute, School of Veterinary Medicine,<institution>University of Wisconsin-Madison</institution>, Madison, WI 53711;</aff><aff id="aff2"><sup>b</sup>Faculty of Veterinary Medicine and</aff><aff id="aff3"><sup>c</sup>Collaborating Research Center-Emerging and Reemerging Infectious Diseases, Tropical Disease Centre,<institution>Airlangga University</institution>, Surabaya 60115,<country>Indonesia</country>;</aff><aff id="aff4"><sup>d</sup>Division of Virology, Department of Microbiology and Immunology and</aff><aff id="aff5"><sup>e</sup>International Research Center for Infectious Diseases, Institute of Medical Science,<institution>University of Tokyo</institution>, Tokyo 108-8639,<country>Japan</country>; and</aff><aff id="aff6"><sup>f</sup>Infection-Induced Host Responses Project,<institution>Exploratory Research for Advanced Technology</institution>, Saitama 332-0012,<country>Japan</country></aff></contrib-group><author-notes><corresp id="cor1"><sup>1</sup>To whom correspondence may be addressed at: Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, 575 Science Drive, Madison, WI 53711. E-mail: <email>kawaokay@svm.vetmed.wisc.edu</email> or <email>mhatta@facstaff.wisc.edu</email>.</corresp><fn fn-type="edited-by"><p>Edited by Robert G. Webster, St. Jude Children’s Research Hospital, Memphis, TN, and approved December 14, 2009 (received for review November 5, 2009)</p></fn><fn fn-type="con"><p>Author contributions: C.L., M.H., S.W., G.N., and Y.K. designed research; C.L., M.H., C.A.N., Y.M., and S.W. performed research; C.L., M.H., S.W., G.N., and Y.K. analyzed data; and C.L., M.H., and Y.K. wrote the paper.</p></fn><fn fn-type="conflict"><p>The authors declare no conflict of interest.</p></fn></author-notes><pub-date pub-type="ppub"><day>9</day><month>3</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>22</day><month>2</month><year>2010</year></pub-date><volume>107</volume><issue>10</issue><fpage>4687</fpage><lpage>4692</lpage><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="pnas.200912807.pdf"></self-uri><abstract><p>The spread of avian H5N1 influenza viruses around the globe has become a worldwide public health concern. To evaluate the pathogenic potential of reassortant viruses between currently cocirculating avian H5N1 and human H3N2 influenza viruses, we generated all the 254 combinations of reassortant viruses between A/chicken/South Kalimantan/UT6028/06 (SK06, H5N1) and A/Tokyo/Ut-Sk-1/07 (Tok07, H3N2) influenza viruses by reverse genetics. We found that the presence of Tok07 PB2 protein in the ribonucleoprotein (RNP) complex allowed efficient viral RNA transcription in a minigenome assay and that RNP activity played an essential role in the viability and replicative ability of the reassortant viruses. When the pathogenicity of 75 reassortant H5 viruses was tested in mice, 22 were more pathogenic than the parental SK06 virus, and three were extremely virulent. Strikingly, all 22 of these viruses obtained their <italic>PB2</italic> segment from Tok07 virus. Further analysis showed that Tok07 <italic>PB1</italic> alone lacked the ability to enhance the pathogenicity of the reassortant viruses but could do so by cooperating with Tok07 <italic>PB2</italic>. Our data demonstrate that reassortment between an avian H5N1 virus with low pathogenicity in mice and a human virus could result in highly pathogenic viruses and that the human virus <italic>PB2</italic> segment functions in the background of an avian H5N1 virus, enhancing its virulence. Our findings highlight the importance of surveillance programs to monitor the emergence of human H5 reassortant viruses, especially those containing a <italic>PB2</italic> segment of human origin.</p></abstract><kwd-group><kwd>influenza reassortants</kwd><kwd>pathogenicity</kwd><kwd>pandemic</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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