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Multi-spectral fluorescent reporter influenza viruses (Color-flu) as powerful tools for in vivo studies

Identifieur interne : 000385 ( Pmc/Checkpoint ); précédent : 000384; suivant : 000386

Multi-spectral fluorescent reporter influenza viruses (Color-flu) as powerful tools for in vivo studies

Auteurs : Satoshi Fukuyama [Japon] ; Hiroaki Katsura [Japon] ; Dongming Zhao [Japon] ; Makoto Ozawa [Japon] ; Tomomi Ando [Japon] ; Jason E. Shoemaker [Japon] ; Izumi Ishikawa [Japon] ; Shinya Yamada [Japon] ; Gabriele Neumann [États-Unis] ; Shinji Watanabe [Japon] ; Hiroaki Kitano [Japon] ; Yoshihiro Kawaoka [Japon, États-Unis]

Source :

RBID : PMC:4389232

Abstract

Seasonal influenza A viruses cause annual epidemics of respiratory disease; highly pathogenic avian H5N1 and the recently emerged H7N9 viruses cause severe infections in humans, often with fatal outcomes. Although numerous studies have addressed the pathogenicity of influenza viruses, influenza pathogenesis remains incompletely understood. Here we generate influenza viruses expressing fluorescent proteins of different colours (‘Color-flu’ viruses) to facilitate the study of viral infection in in vivo models. On adaptation to mice, stable expression of the fluorescent proteins in infected animals allows their detection by different types of microscopy and by flow cytometry. We use this system to analyse the progression of viral spread in mouse lungs, for live imaging of virus-infected cells, and for differential gene expression studies in virus antigen-positive and virus antigen-negative live cells in the lungs of Color-flu-infected mice. Collectively, Color-flu viruses are powerful tools to analyse virus infections at the cellular level in vivo to better understand influenza pathogenesis.


Url:
DOI: 10.1038/ncomms7600
PubMed: 25807527
PubMed Central: 4389232


Affiliations:


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PMC:4389232

Le document en format XML

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<name sortKey="Ando, Tomomi" sort="Ando, Tomomi" uniqKey="Ando T" first="Tomomi" last="Ando">Tomomi Ando</name>
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<name sortKey="Yamada, Shinya" sort="Yamada, Shinya" uniqKey="Yamada S" first="Shinya" last="Yamada">Shinya Yamada</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author>
<name sortKey="Kitano, Hiroaki" sort="Kitano, Hiroaki" uniqKey="Kitano H" first="Hiroaki" last="Kitano">Hiroaki Kitano</name>
<affiliation wicri:level="1">
<nlm:aff id="a1">
<institution>Exploratory Research for Advanced Technology Infection-Induced Host Responses Project, Japan Science and Technology Agency (JST)</institution>
, Kawaguchi, Saitama 332-0012,
<country>Japan</country>
</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="a7">
<institution>The Systems Biology Institute</institution>
, Minato-ku, Tokyo 108-0071,
<country>Japan</country>
</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="a8">
<institution>Sony Computer Science Laboratories</institution>
, Shinagawa-ku, Tokyo 141-0022,
<country>Japan</country>
</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="a9">
<institution>Okinawa Institute of Science and Technology Graduate University</institution>
, Onna-son, Okinawa 904-0495,
<country>Japan</country>
</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name>
<affiliation wicri:level="1">
<nlm:aff id="a1">
<institution>Exploratory Research for Advanced Technology Infection-Induced Host Responses Project, Japan Science and Technology Agency (JST)</institution>
, Kawaguchi, Saitama 332-0012,
<country>Japan</country>
</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
<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="1">
<nlm:aff id="a2">
<institution>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo</institution>
, Minato-ku, Tokyo 108-8639,
<country>Japan</country>
</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
<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="1">
<nlm:aff id="a5">
<institution>Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison</institution>
, Madison, Wisconsin 53711,
<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
<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="a10">
<institution>Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo</institution>
, Minato-ku, Tokyo 108-8639,
<country>Japan</country>
</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
<placeName>
<settlement type="city">Tokyo</settlement>
<region type="province">Région de Kantō</region>
</placeName>
<orgName type="university" n="3">Université de Tokyo</orgName>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Nature Communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint>
<date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>Seasonal influenza A viruses cause annual epidemics of respiratory disease; highly pathogenic avian H5N1 and the recently emerged H7N9 viruses cause severe infections in humans, often with fatal outcomes. Although numerous studies have addressed the pathogenicity of influenza viruses, influenza pathogenesis remains incompletely understood. Here we generate influenza viruses expressing fluorescent proteins of different colours (‘Color-flu’ viruses) to facilitate the study of viral infection in
<italic>in vivo</italic>
models. On adaptation to mice, stable expression of the fluorescent proteins in infected animals allows their detection by different types of microscopy and by flow cytometry. We use this system to analyse the progression of viral spread in mouse lungs, for live imaging of virus-infected cells, and for differential gene expression studies in virus antigen-positive and virus antigen-negative live cells in the lungs of Color-flu-infected mice. Collectively, Color-flu viruses are powerful tools to analyse virus infections at the cellular level
<italic>in vivo</italic>
to better understand influenza pathogenesis.</p>
</div>
</front>
<back>
<div1 type="bibliography">
<listBibl>
<biblStruct>
<analytic>
<author>
<name sortKey="Wright, P F" uniqKey="Wright P">P. F. Wright</name>
</author>
<author>
<name sortKey="Neumann, G" uniqKey="Neumann G">G. Neumann</name>
</author>
<author>
<name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y. Kawaoka</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Watanabe, T" uniqKey="Watanabe T">T. Watanabe</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Zhang, Q" uniqKey="Zhang Q">Q. Zhang</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Yu, W C" uniqKey="Yu W">W. C. Yu</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Diebold, S S" uniqKey="Diebold S">S. S. Diebold</name>
</author>
<author>
<name sortKey="Kaisho, T" uniqKey="Kaisho T">T. Kaisho</name>
</author>
<author>
<name sortKey="Hemmi, H" uniqKey="Hemmi H">H. Hemmi</name>
</author>
<author>
<name sortKey="Akira, S" uniqKey="Akira S">S. Akira</name>
</author>
<author>
<name sortKey="Reis E Sousa, C" uniqKey="Reis E Sousa C">C. Reis e Sousa</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Pichlmair, A" uniqKey="Pichlmair A">A. Pichlmair</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Honda, K" uniqKey="Honda K">K. Honda</name>
</author>
<author>
<name sortKey="Taniguchi, T" uniqKey="Taniguchi T">T. Taniguchi</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Garcia Sastre, A" uniqKey="Garcia Sastre A">A. Garcia-Sastre</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Herold, S" uniqKey="Herold S">S. Herold</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Perrone, L A" uniqKey="Perrone L">L. A. Perrone</name>
</author>
<author>
<name sortKey="Plowden, J K" uniqKey="Plowden J">J. K. Plowden</name>
</author>
<author>
<name sortKey="Garcia Sastre, A" uniqKey="Garcia Sastre A">A. Garcia-Sastre</name>
</author>
<author>
<name sortKey="Katz, J M" uniqKey="Katz J">J. M. Katz</name>
</author>
<author>
<name sortKey="Tumpey, T M" uniqKey="Tumpey T">T. M. Tumpey</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Fukuyama, S" uniqKey="Fukuyama S">S. Fukuyama</name>
</author>
<author>
<name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y. Kawaoka</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Kittel, C" uniqKey="Kittel C">C. Kittel</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Shinya, K" uniqKey="Shinya K">K. Shinya</name>
</author>
<author>
<name sortKey="Fujii, Y" uniqKey="Fujii Y">Y. Fujii</name>
</author>
<author>
<name sortKey="Ito, H" uniqKey="Ito H">H. Ito</name>
</author>
<author>
<name sortKey="Ito, T" uniqKey="Ito T">T. Ito</name>
</author>
<author>
<name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y. Kawaoka</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Manicassamy, B" uniqKey="Manicassamy B">B. Manicassamy</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Helft, J" uniqKey="Helft J">J. Helft</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Nagai, T" uniqKey="Nagai T">T. Nagai</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Patterson, G" uniqKey="Patterson G">G. Patterson</name>
</author>
<author>
<name sortKey="Day, R N" uniqKey="Day R">R. N. Day</name>
</author>
<author>
<name sortKey="Piston, D" uniqKey="Piston D">D. Piston</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Shaner, N C" uniqKey="Shaner N">N. C. Shaner</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Go, J T" uniqKey="Go J">J. T. Go</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Zhao, D" uniqKey="Zhao D">D. Zhao</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Salomon, R" uniqKey="Salomon R">R. Salomon</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Hatta, M" uniqKey="Hatta M">M. Hatta</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Weissleder, R" uniqKey="Weissleder R">R. Weissleder</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Jobsis, F F" uniqKey="Jobsis F">F. F. Jobsis</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Tran, V" uniqKey="Tran V">V. Tran</name>
</author>
<author>
<name sortKey="Moser, L A" uniqKey="Moser L">L. A. Moser</name>
</author>
<author>
<name sortKey="Poole, D S" uniqKey="Poole D">D. S. Poole</name>
</author>
<author>
<name sortKey="Mehle, A" uniqKey="Mehle A">A. Mehle</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Pan, W" uniqKey="Pan W">W. Pan</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Heaton, N S" uniqKey="Heaton N">N. S. Heaton</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Ghaznavi, F" uniqKey="Ghaznavi F">F. Ghaznavi</name>
</author>
<author>
<name sortKey="Evans, A" uniqKey="Evans A">A. Evans</name>
</author>
<author>
<name sortKey="Madabhushi, A" uniqKey="Madabhushi A">A. Madabhushi</name>
</author>
<author>
<name sortKey="Feldman, M" uniqKey="Feldman M">M. Feldman</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Scholtissek, C" uniqKey="Scholtissek C">C. Scholtissek</name>
</author>
<author>
<name sortKey="Rohde, W" uniqKey="Rohde W">W. Rohde</name>
</author>
<author>
<name sortKey="Von Hoyningen, V" uniqKey="Von Hoyningen V">V. Von Hoyningen</name>
</author>
<author>
<name sortKey="Rott, R" uniqKey="Rott R">R. Rott</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y. Kawaoka</name>
</author>
<author>
<name sortKey="Krauss, S" uniqKey="Krauss S">S. Krauss</name>
</author>
<author>
<name sortKey="Webster, R G" uniqKey="Webster R">R. G. Webster</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Smith, G J" uniqKey="Smith G">G. J. Smith</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Itoh, Y" uniqKey="Itoh Y">Y. Itoh</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Gambotto, A" uniqKey="Gambotto A">A. Gambotto</name>
</author>
<author>
<name sortKey="Barratt Boyes, S M" uniqKey="Barratt Boyes S">S. M. Barratt-Boyes</name>
</author>
<author>
<name sortKey="De Jong, M D" uniqKey="De Jong M">M. D. de Jong</name>
</author>
<author>
<name sortKey="Neumann, G" uniqKey="Neumann G">G. Neumann</name>
</author>
<author>
<name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y. Kawaoka</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Shieh, W J" uniqKey="Shieh W">W. J. Shieh</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Basler, C F" uniqKey="Basler C">C. F. Basler</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Neumann, G" uniqKey="Neumann G">G. Neumann</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Smyth, G K" uniqKey="Smyth G">G. K. Smyth</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Kaimal, V" uniqKey="Kaimal V">V. Kaimal</name>
</author>
<author>
<name sortKey="Bardes, E E" uniqKey="Bardes E">E. E. Bardes</name>
</author>
<author>
<name sortKey="Tabar, S C" uniqKey="Tabar S">S. C. Tabar</name>
</author>
<author>
<name sortKey="Jegga, A G" uniqKey="Jegga A">A. G. Jegga</name>
</author>
<author>
<name sortKey="Aronow, B J" uniqKey="Aronow B">B. J. Aronow</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">Nat Commun</journal-id>
<journal-id journal-id-type="iso-abbrev">Nat Commun</journal-id>
<journal-title-group>
<journal-title>Nature Communications</journal-title>
</journal-title-group>
<issn pub-type="epub">2041-1723</issn>
<publisher>
<publisher-name>Nature Pub. Group</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">25807527</article-id>
<article-id pub-id-type="pmc">4389232</article-id>
<article-id pub-id-type="pii">ncomms7600</article-id>
<article-id pub-id-type="doi">10.1038/ncomms7600</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Multi-spectral fluorescent reporter influenza viruses (Color-flu) as powerful tools for
<italic>in vivo</italic>
studies</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Fukuyama</surname>
<given-names>Satoshi</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
<xref ref-type="author-notes" rid="n1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Katsura</surname>
<given-names>Hiroaki</given-names>
</name>
<xref ref-type="aff" rid="a2">2</xref>
<xref ref-type="author-notes" rid="n1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zhao</surname>
<given-names>Dongming</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
<xref ref-type="author-notes" rid="n1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ozawa</surname>
<given-names>Makoto</given-names>
</name>
<xref ref-type="aff" rid="a3">3</xref>
<xref ref-type="aff" rid="a4">4</xref>
<xref ref-type="author-notes" rid="n1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ando</surname>
<given-names>Tomomi</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Shoemaker</surname>
<given-names>Jason E.</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ishikawa</surname>
<given-names>Izumi</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yamada</surname>
<given-names>Shinya</given-names>
</name>
<xref ref-type="aff" rid="a2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Neumann</surname>
<given-names>Gabriele</given-names>
</name>
<xref ref-type="aff" rid="a5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Watanabe</surname>
<given-names>Shinji</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kitano</surname>
<given-names>Hiroaki</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a7">7</xref>
<xref ref-type="aff" rid="a8">8</xref>
<xref ref-type="aff" rid="a9">9</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kawaoka</surname>
<given-names>Yoshihiro</given-names>
</name>
<xref ref-type="corresp" rid="c1">a</xref>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
<xref ref-type="aff" rid="a5">5</xref>
<xref ref-type="aff" rid="a10">10</xref>
</contrib>
<aff id="a1">
<label>1</label>
<institution>Exploratory Research for Advanced Technology Infection-Induced Host Responses Project, Japan Science and Technology Agency (JST)</institution>
, Kawaguchi, Saitama 332-0012,
<country>Japan</country>
</aff>
<aff id="a2">
<label>2</label>
<institution>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo</institution>
, Minato-ku, Tokyo 108-8639,
<country>Japan</country>
</aff>
<aff id="a3">
<label>3</label>
<institution>Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University</institution>
, Kagoshima 890-0065,
<country>Japan</country>
</aff>
<aff id="a4">
<label>4</label>
<institution>Transboundary Animal Distance Center, Joint Faculty of Veterinary Medicine, Kagoshima University</institution>
, Kagoshima 890-0065,
<country>Japan</country>
</aff>
<aff id="a5">
<label>5</label>
<institution>Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison</institution>
, Madison, Wisconsin 53711,
<country>USA</country>
</aff>
<aff id="a6">
<label>6</label>
<institution>Laboratory of Veterinary Microbiology, Department of Veterinary Sciences, University of Miyazaki</institution>
, Miyazaki 889-2192,
<country>Japan</country>
</aff>
<aff id="a7">
<label>7</label>
<institution>The Systems Biology Institute</institution>
, Minato-ku, Tokyo 108-0071,
<country>Japan</country>
</aff>
<aff id="a8">
<label>8</label>
<institution>Sony Computer Science Laboratories</institution>
, Shinagawa-ku, Tokyo 141-0022,
<country>Japan</country>
</aff>
<aff id="a9">
<label>9</label>
<institution>Okinawa Institute of Science and Technology Graduate University</institution>
, Onna-son, Okinawa 904-0495,
<country>Japan</country>
</aff>
<aff id="a10">
<label>10</label>
<institution>Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo</institution>
, Minato-ku, Tokyo 108-8639,
<country>Japan</country>
</aff>
</contrib-group>
<author-notes>
<corresp id="c1">
<label>a</label>
<email>kawaoka@ims.u-tokyo.ac.jp</email>
</corresp>
<fn id="n1">
<label>*</label>
<p>These authors contributed equally to this work</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>25</day>
<month>03</month>
<year>2015</year>
</pub-date>
<volume>6</volume>
<elocation-id>6600</elocation-id>
<history>
<date date-type="received">
<day>23</day>
<month>08</month>
<year>2014</year>
</date>
<date date-type="accepted">
<day>10</day>
<month>02</month>
<year>2015</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</copyright-statement>
<copyright-year>2015</copyright-year>
<copyright-holder>Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/">
<pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
</license-p>
</license>
</permissions>
<abstract>
<p>Seasonal influenza A viruses cause annual epidemics of respiratory disease; highly pathogenic avian H5N1 and the recently emerged H7N9 viruses cause severe infections in humans, often with fatal outcomes. Although numerous studies have addressed the pathogenicity of influenza viruses, influenza pathogenesis remains incompletely understood. Here we generate influenza viruses expressing fluorescent proteins of different colours (‘Color-flu’ viruses) to facilitate the study of viral infection in
<italic>in vivo</italic>
models. On adaptation to mice, stable expression of the fluorescent proteins in infected animals allows their detection by different types of microscopy and by flow cytometry. We use this system to analyse the progression of viral spread in mouse lungs, for live imaging of virus-infected cells, and for differential gene expression studies in virus antigen-positive and virus antigen-negative live cells in the lungs of Color-flu-infected mice. Collectively, Color-flu viruses are powerful tools to analyse virus infections at the cellular level
<italic>in vivo</italic>
to better understand influenza pathogenesis.</p>
</abstract>
<abstract abstract-type="web-summary">
<p>
<inline-graphic id="i1" xlink:href="ncomms7600-i1.jpg"></inline-graphic>
Animal models are important to study organismal immune responses to infection with influenza viruses. Here, Fukuyama
<italic>et al.</italic>
report a new generation of fluorescently labelled influenza viruses that facilitate the study of viral infections in animal models at cellular level.</p>
</abstract>
</article-meta>
</front>
<floats-group>
<fig id="f1">
<label>Figure 1</label>
<caption>
<title>Characteristics of mouse-adapted Venus-PR8 in mice.</title>
<p>Four B6 mice per group were intranasally inoculated with WT-PR8, WT-Venus-PR8 or MA-Venus-PR8. Body weight and survival of mice were monitored for 14 days.</p>
</caption>
<graphic xlink:href="ncomms7600-f1"></graphic>
</fig>
<fig id="f2">
<label>Figure 2</label>
<caption>
<title>Distribution of Color-flu viruses in lungs.</title>
<p>(
<bold>a</bold>
) Lung tissues were harvested from B6 mice at days 3 and 5 p.i. with Color-flu viruses (10
<sup>5</sup>
PFU of MA-eCFP, eGFP, Venus and mCherry-PR8). Whole-mount images of transparent lung tissues were obtained by using a fluorescent stereomicroscope. Scale bar, 5 mm. (
<bold>b</bold>
,
<bold>c</bold>
) B6 mice were intranasally inoculated with a mixture of MA-eCFP, eGFP, Venus and mCherry-PR8 (2.5 × 10
<sup>4</sup>
PFU per strain). (
<bold>b</bold>
) The sections of lungs at days 2 and 5 p.i. were analysed by using an inverted fluorescence microscope with a Nuance FX multispectral imaging system with inForm software. Scale bar, 100 μm. (
<bold>c</bold>
) Enlarged images of the indicated area in (
<bold>b</bold>
) were unmixed and separated into autofluorescence (AF), eCFP, eGFP, Venus and mCherry fluorescence. Arrows in the merged image indicate cells infected with different colour variants of Color-flu viruses.</p>
</caption>
<graphic xlink:href="ncomms7600-f2"></graphic>
</fig>
<fig id="f3">
<label>Figure 3</label>
<caption>
<title>Analysis of lung macrophages.</title>
<p>(
<bold>a</bold>
) Analysis of macrophage infiltration. Fixed lung sections of PBS-inoculated mice (mock) or mice infected with 10
<sup>5</sup>
PFU of MA-Venus-PR8 at day 2 p.i. were incubated with an PE-anti-Mac3 antibody (red) and Hoechst dye (blue). The Venus fluorescent signal is shown in green. Scale bar, 200 μm. (
<bold>b</bold>
) Kinetics of the interactions between virus-infected cells and lung macrophages. Images of eGFP-positive cells (green) and CD11b+ macrophages (red) in lung tissue from naive B6 mice (upper left panel) and B6 mice on day 3 p.i. with 10
<sup>5</sup>
PFU of MA-eGFP-PR8 (upper right panel) were obtained by using a two-photon microscope. The tracks of individual macrophages are indicated as coloured lines. Sequential images in the lower panel (1–4) show an enlarged view of the box in the upper right panel. Arrowheads indicate the blebbing of eGFP-positive cells. Scale bar, 40 μm. (
<bold>c</bold>
) Infection of macrophages by influenza viruses. Single-cell suspensions were obtained from lungs of PBS-inoculated (mock) mice or mice infected with 10
<sup>5</sup>
PFU of MA-Venus-PR8 at day 3 p.i., The FACS analysis shows Venus expression from cells gated on F4/80 and CD45 expression levels. (
<bold>d</bold>
,
<bold>e</bold>
) Gene expression analysis. Total RNA was isolated from sorted macrophages of PBS-inoculated (naive) mice, and from sorted Venus-positive (Venus(+)) and Venus-negative (Venus(−)) macrophages of mice inoculated with 10
<sup>5</sup>
PFU of MA-Venus-PR8 at day 3 p.i. (9 mice per treatment), and microarray analysis was performed. (
<bold>d</bold>
) Differentially expressed (DE) transcripts were identified by comparing gene expression levels in naive macrophages with those in Venus(+) and Venus(−) macrophages from infected mice. A heat map of the clustered transcripts for each condition is displayed, with enriched annotations and the enrichment scores for each cluster. A shift of the blue line in the heat map to the left or right indicates that the DE transcript is more highly expressed in Venus(+) or Venus(−) macrophages, respectively. (
<bold>e</bold>
) Heat map comparing expression levels of type I interferons (IFNs) between Venus(+) and Venus(−) macrophages. NS denotes not statistically significant between Venus(−) cells from infected animals and naive macrophages from uninfected animals.</p>
</caption>
<graphic xlink:href="ncomms7600-f3"></graphic>
</fig>
<fig id="f4">
<label>Figure 4</label>
<caption>
<title>Characterization of MA-Venus-HPAI virus.</title>
<p>(
<bold>a</bold>
) Four B6 mice per group were intranasally inoculated with MA-Venus-HPAI virus. Mouse body weight and survival were monitored for 14 days. (
<bold>b</bold>
) Lungs, spleens, kidneys and brains were harvested from B6 mice at day 3 p.i. with 10
<sup>5</sup>
PFU of MA-Venus-HPAI virus. Virus titres of tissue homogenates were determined by use of plaque assays in MDCK cells. Each data point represents the mean±s.d. (
<italic>n</italic>
=3). (
<bold>c</bold>
,
<bold>d</bold>
) Lung tissues were harvested from B6 mice at day 1 and 2 p.i. with 10
<sup>5</sup>
PFU of MA-Venus-HPAI and PR8. Images of transparent lung tissues with Venus-positive cells in the bronchus (red) and alveolar area (green) were obtained by using a two-photon microscope. Each data point represents the mean±s.d. (
<italic>n</italic>
=3). Statistical significance was calculated by using the Student’s
<italic>t</italic>
-test. (
<bold>d</bold>
) The distribution of Venus-positive cells was evaluated via volume analysis of the Venus-positive bronchus and alveolar area by using 3D images of the transparent lung tissues. (
<bold>e</bold>
,
<bold>f</bold>
) Cells were collected from lungs of B6 mice at days 1, 2, 3 and 4 p.i. with 10
<sup>5</sup>
PFU of MA-Venus-PR8 or MA-Venus-HPAI virus, and stained for CD45, CD11b and F4/80. Venus expression in CD45-negative cells, and the Venus versus F4/80 staining profile gated on CD45-positive cells were analysed by flow cytometry. (
<bold>e</bold>
) A representative dot plot from day 2 p.i. is shown with the percentage of Venus-positive cells.</p>
</caption>
<graphic xlink:href="ncomms7600-f4"></graphic>
</fig>
<table-wrap position="float" id="t1">
<label>Table 1</label>
<caption>
<title>Replication and virulence of Color-flu in mice
<xref ref-type="fn" rid="t1-fn1">*</xref>
.</title>
</caption>
<table frame="hsides" rules="groups" border="1">
<colgroup>
<col align="left"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
<col align="center"></col>
</colgroup>
<thead valign="bottom">
<tr>
<th align="left" valign="top" charoff="50">
<bold>Virus</bold>
</th>
<th colspan="3" align="center" valign="top" char="±" charoff="50">
<bold>Mean virus titer (log</bold>
<sub>
<bold>10</bold>
</sub>
<bold>PFU/g±s.d.) in the mouse lung on the indicated day p.i.</bold>
<hr></hr>
</th>
<th align="center" valign="top" charoff="50">
<bold>MLD</bold>
<sub>
<bold>50</bold>
</sub>
<bold>(PFU)</bold>
</th>
</tr>
<tr>
<th align="left" valign="top" charoff="50"> </th>
<th align="center" valign="top" char="±" charoff="50">
<bold>Day 3 p.i.</bold>
</th>
<th align="center" valign="top" char="±" charoff="50">
<bold>Day 5 p.i.</bold>
</th>
<th align="center" valign="top" char="±" charoff="50">
<bold>Day 7 p.i.</bold>
</th>
<th align="center" valign="top" charoff="50"> </th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left" valign="top" charoff="50">MA-eCFP-PR8</td>
<td align="char" valign="top" char="±" charoff="50">8.1±0.2
<xref ref-type="fn" rid="t1-fn2"></xref>
</td>
<td align="char" valign="top" char="±" charoff="50">8.0±0.1</td>
<td align="char" valign="top" char="±" charoff="50">6.3±0.1</td>
<td align="center" valign="top" charoff="50">10
<sup>3.0</sup>
</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">MA-eGFP-PR8</td>
<td align="char" valign="top" char="±" charoff="50">8.6±0.1</td>
<td align="char" valign="top" char="±" charoff="50">8.3±0.1</td>
<td align="char" valign="top" char="±" charoff="50">6.3±0.1</td>
<td align="center" valign="top" charoff="50">10
<sup>3.5</sup>
</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">MA-Venus-PR8</td>
<td align="char" valign="top" char="±" charoff="50">8.6±0.2</td>
<td align="char" valign="top" char="±" charoff="50">8.4±0.1</td>
<td align="char" valign="top" char="±" charoff="50">6.5±0.3</td>
<td align="center" valign="top" charoff="50">10
<sup>3.3</sup>
</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">MA-mCherry-PR8</td>
<td align="char" valign="top" char="±" charoff="50">7.7±0.3
<xref ref-type="fn" rid="t1-fn2"></xref>
</td>
<td align="char" valign="top" char="±" charoff="50">7.5±0.7</td>
<td align="char" valign="top" char="±" charoff="50">6.1±0.4</td>
<td align="center" valign="top" charoff="50">10
<sup>2.7</sup>
</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">WT-Venus-PR8</td>
<td align="char" valign="top" char="±" charoff="50">5.6±0.3
<xref ref-type="fn" rid="t1-fn2"></xref>
</td>
<td align="char" valign="top" char="±" charoff="50">5.3±0.3
<xref ref-type="fn" rid="t1-fn2"></xref>
</td>
<td align="char" valign="top" char="±" charoff="50">5.2±0.2
<xref ref-type="fn" rid="t1-fn2"></xref>
</td>
<td align="center" valign="top" charoff="50">>10
<sup>4.3</sup>
</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">WT-PR8</td>
<td align="char" valign="top" char="±" charoff="50">8.8±0.1</td>
<td align="char" valign="top" char="±" charoff="50">8.2±0.5</td>
<td align="char" valign="top" char="±" charoff="50">6.9±0.2</td>
<td align="center" valign="top" charoff="50">10
<sup>2.5</sup>
</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">MA-PR8</td>
<td align="char" valign="top" char="±" charoff="50">8.9±0.1</td>
<td align="char" valign="top" char="±" charoff="50">9.0±0.0</td>
<td align="char" valign="top" char="±" charoff="50">7.9±0.2
<xref ref-type="fn" rid="t1-fn2"></xref>
</td>
<td align="center" valign="top" charoff="50">10
<sup>2.3</sup>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="t1-fn1">
<p>
<sup>*</sup>
B6 mice were inoculated intranasally with 10
<sup>4</sup>
PFU of each virus in a 50 μl volume. Three mice from each group were killed on days 3, 5 and 7 p.i., and virus titres in the lungs were determined in MDCK cells.</p>
</fn>
<fn id="t1-fn2">
<p>
<sup></sup>
Statistical significance was calculated by using the Student’s
<italic>t</italic>
-test; the
<italic>P</italic>
value was <0.01 compared with the titres in the lungs of mice infected with WT-PR8 virus.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
<affiliations>
<list>
<country>
<li>Japon</li>
<li>États-Unis</li>
</country>
<region>
<li>Région de Kantō</li>
<li>Wisconsin</li>
</region>
<settlement>
<li>Madison (Wisconsin)</li>
<li>Tokyo</li>
</settlement>
<orgName>
<li>Université de Tokyo</li>
<li>Université du Wisconsin à Madison</li>
</orgName>
</list>
<tree>
<country name="Japon">
<noRegion>
<name sortKey="Fukuyama, Satoshi" sort="Fukuyama, Satoshi" uniqKey="Fukuyama S" first="Satoshi" last="Fukuyama">Satoshi Fukuyama</name>
</noRegion>
<name sortKey="Ando, Tomomi" sort="Ando, Tomomi" uniqKey="Ando T" first="Tomomi" last="Ando">Tomomi Ando</name>
<name sortKey="Ando, Tomomi" sort="Ando, Tomomi" uniqKey="Ando T" first="Tomomi" last="Ando">Tomomi Ando</name>
<name sortKey="Fukuyama, Satoshi" sort="Fukuyama, Satoshi" uniqKey="Fukuyama S" first="Satoshi" last="Fukuyama">Satoshi Fukuyama</name>
<name sortKey="Ishikawa, Izumi" sort="Ishikawa, Izumi" uniqKey="Ishikawa I" first="Izumi" last="Ishikawa">Izumi Ishikawa</name>
<name sortKey="Ishikawa, Izumi" sort="Ishikawa, Izumi" uniqKey="Ishikawa I" first="Izumi" last="Ishikawa">Izumi Ishikawa</name>
<name sortKey="Katsura, Hiroaki" sort="Katsura, Hiroaki" uniqKey="Katsura H" first="Hiroaki" last="Katsura">Hiroaki Katsura</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="Kitano, Hiroaki" sort="Kitano, Hiroaki" uniqKey="Kitano H" first="Hiroaki" last="Kitano">Hiroaki Kitano</name>
<name sortKey="Kitano, Hiroaki" sort="Kitano, Hiroaki" uniqKey="Kitano H" first="Hiroaki" last="Kitano">Hiroaki Kitano</name>
<name sortKey="Kitano, Hiroaki" sort="Kitano, Hiroaki" uniqKey="Kitano H" first="Hiroaki" last="Kitano">Hiroaki Kitano</name>
<name sortKey="Kitano, Hiroaki" sort="Kitano, Hiroaki" uniqKey="Kitano H" first="Hiroaki" last="Kitano">Hiroaki Kitano</name>
<name sortKey="Ozawa, Makoto" sort="Ozawa, Makoto" uniqKey="Ozawa M" first="Makoto" last="Ozawa">Makoto Ozawa</name>
<name sortKey="Ozawa, Makoto" sort="Ozawa, Makoto" uniqKey="Ozawa M" first="Makoto" last="Ozawa">Makoto Ozawa</name>
<name sortKey="Shoemaker, Jason E" sort="Shoemaker, Jason E" uniqKey="Shoemaker J" first="Jason E." last="Shoemaker">Jason E. Shoemaker</name>
<name sortKey="Shoemaker, Jason E" sort="Shoemaker, Jason E" uniqKey="Shoemaker J" first="Jason E." last="Shoemaker">Jason E. Shoemaker</name>
<name sortKey="Watanabe, Shinji" sort="Watanabe, Shinji" uniqKey="Watanabe S" first="Shinji" last="Watanabe">Shinji Watanabe</name>
<name sortKey="Watanabe, Shinji" sort="Watanabe, Shinji" uniqKey="Watanabe S" first="Shinji" last="Watanabe">Shinji Watanabe</name>
<name sortKey="Yamada, Shinya" sort="Yamada, Shinya" uniqKey="Yamada S" first="Shinya" last="Yamada">Shinya Yamada</name>
<name sortKey="Zhao, Dongming" sort="Zhao, Dongming" uniqKey="Zhao D" first="Dongming" last="Zhao">Dongming Zhao</name>
<name sortKey="Zhao, Dongming" sort="Zhao, Dongming" uniqKey="Zhao D" first="Dongming" last="Zhao">Dongming Zhao</name>
</country>
<country name="États-Unis">
<noRegion>
<name sortKey="Neumann, Gabriele" sort="Neumann, Gabriele" uniqKey="Neumann G" first="Gabriele" last="Neumann">Gabriele Neumann</name>
</noRegion>
<name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name>
</country>
</tree>
</affiliations>
</record>

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