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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock</title><author><name sortKey="Rudd, Penny A" sort="Rudd, Penny A" uniqKey="Rudd P" first="Penny A." last="Rudd">Penny A. Rudd</name><affiliation><nlm:aff id="aff1">Queensland Institute of Medical Research, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Australian Infectious Diseases Research Centre, School of Chemistry & Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Wilson, Jane" sort="Wilson, Jane" uniqKey="Wilson J" first="Jane" last="Wilson">Jane Wilson</name><affiliation><nlm:aff id="aff1">Queensland Institute of Medical Research, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">School of Medicine, University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Gardner, Joy" sort="Gardner, Joy" uniqKey="Gardner J" first="Joy" last="Gardner">Joy Gardner</name><affiliation><nlm:aff id="aff1">Queensland Institute of Medical Research, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Larcher, Thibaut" sort="Larcher, Thibaut" uniqKey="Larcher T" first="Thibaut" last="Larcher">Thibaut Larcher</name><affiliation><nlm:aff id="aff4">Institut National de Recherche Agronomique, Unité Mixte de Recherche 703, Ecole Nationale Vétérinaire, Nantes, France</nlm:aff></affiliation></author><author><name sortKey="Babarit, Candice" sort="Babarit, Candice" uniqKey="Babarit C" first="Candice" last="Babarit">Candice Babarit</name><affiliation><nlm:aff id="aff4">Institut National de Recherche Agronomique, Unité Mixte de Recherche 703, Ecole Nationale Vétérinaire, Nantes, France</nlm:aff></affiliation></author><author><name sortKey="Le, Thuy T" sort="Le, Thuy T" uniqKey="Le T" first="Thuy T." last="Le">Thuy T. Le</name><affiliation><nlm:aff id="aff1">Queensland Institute of Medical Research, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Anraku, Itaru" sort="Anraku, Itaru" uniqKey="Anraku I" first="Itaru" last="Anraku">Itaru Anraku</name><affiliation><nlm:aff id="aff1">Queensland Institute of Medical Research, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Kumagai, Yutaro" sort="Kumagai, Yutaro" uniqKey="Kumagai Y" first="Yutaro" last="Kumagai">Yutaro Kumagai</name><affiliation><nlm:aff id="aff5">Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan</nlm:aff></affiliation></author><author><name sortKey="Loo, Yueh Ming" sort="Loo, Yueh Ming" uniqKey="Loo Y" first="Yueh-Ming" last="Loo">Yueh-Ming Loo</name><affiliation><nlm:aff id="aff6">Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA</nlm:aff></affiliation></author><author><name sortKey="Gale, Michael" sort="Gale, Michael" uniqKey="Gale M" first="Michael" last="Gale">Michael Gale</name><affiliation><nlm:aff id="aff6">Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA</nlm:aff></affiliation></author><author><name sortKey="Akira, Shizuo" sort="Akira, Shizuo" uniqKey="Akira S" first="Shizuo" last="Akira">Shizuo Akira</name><affiliation><nlm:aff id="aff5">Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan</nlm:aff></affiliation></author><author><name sortKey="Khromykh, Alexander A" sort="Khromykh, Alexander A" uniqKey="Khromykh A" first="Alexander A." last="Khromykh">Alexander A. Khromykh</name><affiliation><nlm:aff id="aff2">Australian Infectious Diseases Research Centre, School of Chemistry & Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Suhrbier, Andreas" sort="Suhrbier, Andreas" uniqKey="Suhrbier A" first="Andreas" last="Suhrbier">Andreas Suhrbier</name><affiliation><nlm:aff id="aff1">Queensland Institute of Medical Research, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Australian Infectious Diseases Research Centre, School of Chemistry & Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22761364</idno><idno type="pmc">3446587</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446587</idno><idno type="RBID">PMC:3446587</idno><idno type="doi">10.1128/JVI.00956-12</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">001A11</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001A11</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock</title><author><name sortKey="Rudd, Penny A" sort="Rudd, Penny A" uniqKey="Rudd P" first="Penny A." last="Rudd">Penny A. Rudd</name><affiliation><nlm:aff id="aff1">Queensland Institute of Medical Research, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Australian Infectious Diseases Research Centre, School of Chemistry & Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Wilson, Jane" sort="Wilson, Jane" uniqKey="Wilson J" first="Jane" last="Wilson">Jane Wilson</name><affiliation><nlm:aff id="aff1">Queensland Institute of Medical Research, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">School of Medicine, University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Gardner, Joy" sort="Gardner, Joy" uniqKey="Gardner J" first="Joy" last="Gardner">Joy Gardner</name><affiliation><nlm:aff id="aff1">Queensland Institute of Medical Research, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Larcher, Thibaut" sort="Larcher, Thibaut" uniqKey="Larcher T" first="Thibaut" last="Larcher">Thibaut Larcher</name><affiliation><nlm:aff id="aff4">Institut National de Recherche Agronomique, Unité Mixte de Recherche 703, Ecole Nationale Vétérinaire, Nantes, France</nlm:aff></affiliation></author><author><name sortKey="Babarit, Candice" sort="Babarit, Candice" uniqKey="Babarit C" first="Candice" last="Babarit">Candice Babarit</name><affiliation><nlm:aff id="aff4">Institut National de Recherche Agronomique, Unité Mixte de Recherche 703, Ecole Nationale Vétérinaire, Nantes, France</nlm:aff></affiliation></author><author><name sortKey="Le, Thuy T" sort="Le, Thuy T" uniqKey="Le T" first="Thuy T." last="Le">Thuy T. Le</name><affiliation><nlm:aff id="aff1">Queensland Institute of Medical Research, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Anraku, Itaru" sort="Anraku, Itaru" uniqKey="Anraku I" first="Itaru" last="Anraku">Itaru Anraku</name><affiliation><nlm:aff id="aff1">Queensland Institute of Medical Research, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Kumagai, Yutaro" sort="Kumagai, Yutaro" uniqKey="Kumagai Y" first="Yutaro" last="Kumagai">Yutaro Kumagai</name><affiliation><nlm:aff id="aff5">Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan</nlm:aff></affiliation></author><author><name sortKey="Loo, Yueh Ming" sort="Loo, Yueh Ming" uniqKey="Loo Y" first="Yueh-Ming" last="Loo">Yueh-Ming Loo</name><affiliation><nlm:aff id="aff6">Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA</nlm:aff></affiliation></author><author><name sortKey="Gale, Michael" sort="Gale, Michael" uniqKey="Gale M" first="Michael" last="Gale">Michael Gale</name><affiliation><nlm:aff id="aff6">Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA</nlm:aff></affiliation></author><author><name sortKey="Akira, Shizuo" sort="Akira, Shizuo" uniqKey="Akira S" first="Shizuo" last="Akira">Shizuo Akira</name><affiliation><nlm:aff id="aff5">Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan</nlm:aff></affiliation></author><author><name sortKey="Khromykh, Alexander A" sort="Khromykh, Alexander A" uniqKey="Khromykh A" first="Alexander A." last="Khromykh">Alexander A. Khromykh</name><affiliation><nlm:aff id="aff2">Australian Infectious Diseases Research Centre, School of Chemistry & Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Suhrbier, Andreas" sort="Suhrbier, Andreas" uniqKey="Suhrbier A" first="Andreas" last="Suhrbier">Andreas Suhrbier</name><affiliation><nlm:aff id="aff1">Queensland Institute of Medical Research, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Australian Infectious Diseases Research Centre, School of Chemistry & Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia</nlm:aff></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="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Chikungunya virus (CHIKV) infections can produce severe disease and mortality. Here we show that CHIKV infection of adult mice deficient in interferon response factors 3 and 7 (IRF3/7<sup>−/−</sup>) is lethal. Mortality was associated with undetectable levels of alpha/beta interferon (IFN-α/β) in serum, ∼50- and ∼10-fold increases in levels of IFN-γ and tumor necrosis factor (TNF), respectively, increased virus replication, edema, vasculitis, hemorrhage, fever followed by hypothermia, oliguria, thrombocytopenia, and raised hematocrits. These features are consistent with hemorrhagic shock and were also evident in infected IFN-α/β receptor-deficient mice. <italic>In situ</italic> hybridization suggested CHIKV infection of endothelium, fibroblasts, skeletal muscle, mononuclear cells, chondrocytes, and keratinocytes in IRF3/7<sup>−/−</sup> mice; all but the latter two stained positive in wild-type mice. Vaccination protected IRF3/7<sup>−/−</sup> mice, suggesting that defective antibody responses were not responsible for mortality. IPS-1- and TRIF-dependent pathways were primarily responsible for IFN-α/β induction, with IRF7 being upregulated >100-fold in infected wild-type mice. These studies suggest that inadequate IFN-α/β responses following virus infection can be sufficient to induce hemorrhagic fever and shock, a finding with implications for understanding severe CHIKV disease and dengue hemorrhagic fever/dengue shock syndrome.</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">22761364</article-id><article-id pub-id-type="pmc">3446587</article-id><article-id pub-id-type="publisher-id">00956-12</article-id><article-id pub-id-type="doi">10.1128/JVI.00956-12</article-id><article-categories><subj-group subj-group-type="heading"><subject>Pathogenesis and Immunity</subject></subj-group></article-categories><title-group><article-title>Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Rudd</surname><given-names>Penny A.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wilson</surname><given-names>Jane</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gardner</surname><given-names>Joy</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Larcher</surname><given-names>Thibaut</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Babarit</surname><given-names>Candice</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Le</surname><given-names>Thuy T.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Anraku</surname><given-names>Itaru</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kumagai</surname><given-names>Yutaro</given-names></name><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Loo</surname><given-names>Yueh-Ming</given-names></name><xref ref-type="aff" rid="aff6"><sup>f</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gale</surname><given-names>Michael</given-names><suffix>Jr.</suffix></name><xref ref-type="aff" rid="aff6"><sup>f</sup></xref></contrib><contrib contrib-type="author"><name><surname>Akira</surname><given-names>Shizuo</given-names></name><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Khromykh</surname><given-names>Alexander A.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Suhrbier</surname><given-names>Andreas</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><aff id="aff1"><label>a</label>Queensland Institute of Medical Research, Brisbane, Queensland, Australia</aff><aff id="aff2"><label>b</label>Australian Infectious Diseases Research Centre, School of Chemistry & Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia</aff><aff id="aff3"><label>c</label>School of Medicine, University of Queensland, Brisbane, Queensland, Australia</aff><aff id="aff4"><label>d</label>Institut National de Recherche Agronomique, Unité Mixte de Recherche 703, Ecole Nationale Vétérinaire, Nantes, France</aff><aff id="aff5"><label>e</label>Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan</aff><aff id="aff6"><label>f</label>Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA</aff></contrib-group><author-notes><corresp>Address correspondence to Andreas Suhrbier, <email>andreasS@qimr.edu.au</email>.</corresp></author-notes><pub-date pub-type="ppub"><month>9</month><year>2012</year></pub-date><volume>86</volume><issue>18</issue><fpage>9888</fpage><lpage>9898</lpage><history><date date-type="received"><day>18</day><month>4</month><year>2012</year></date><date date-type="accepted"><day>25</day><month>6</month><year>2012</year></date></history><permissions><copyright-statement>Copyright © 2012, American Society for Microbiology. All Rights Reserved.</copyright-statement><copyright-year>2012</copyright-year><copyright-holder>American Society for Microbiology</copyright-holder></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zjv01812009888.pdf"></self-uri><abstract><p>Chikungunya virus (CHIKV) infections can produce severe disease and mortality. Here we show that CHIKV infection of adult mice deficient in interferon response factors 3 and 7 (IRF3/7<sup>−/−</sup>) is lethal. Mortality was associated with undetectable levels of alpha/beta interferon (IFN-α/β) in serum, ∼50- and ∼10-fold increases in levels of IFN-γ and tumor necrosis factor (TNF), respectively, increased virus replication, edema, vasculitis, hemorrhage, fever followed by hypothermia, oliguria, thrombocytopenia, and raised hematocrits. These features are consistent with hemorrhagic shock and were also evident in infected IFN-α/β receptor-deficient mice. <italic>In situ</italic> hybridization suggested CHIKV infection of endothelium, fibroblasts, skeletal muscle, mononuclear cells, chondrocytes, and keratinocytes in IRF3/7<sup>−/−</sup> mice; all but the latter two stained positive in wild-type mice. Vaccination protected IRF3/7<sup>−/−</sup> mice, suggesting that defective antibody responses were not responsible for mortality. IPS-1- and TRIF-dependent pathways were primarily responsible for IFN-α/β induction, with IRF7 being upregulated >100-fold in infected wild-type mice. These studies suggest that inadequate IFN-α/β responses following virus infection can be sufficient to induce hemorrhagic fever and shock, a finding with implications for understanding severe CHIKV disease and dengue hemorrhagic fever/dengue shock syndrome.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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