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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Inhibition of NF-κB-Mediated Inflammation in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice Increases Survival</title><author><name sortKey="Dediego, Marta L" sort="Dediego, Marta L" uniqKey="Dediego M" first="Marta L." last="Dediego">Marta L. Dediego</name><affiliation><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Nieto Torres, Jose L" sort="Nieto Torres, Jose L" uniqKey="Nieto Torres J" first="Jose L." last="Nieto-Torres">Jose L. Nieto-Torres</name><affiliation><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Regla Nava, Jose A" sort="Regla Nava, Jose A" uniqKey="Regla Nava J" first="Jose A." last="Regla-Nava">Jose A. Regla-Nava</name><affiliation><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Jimenez Guarde O, Jose M" sort="Jimenez Guarde O, Jose M" uniqKey="Jimenez Guarde O J" first="Jose M." last="Jimenez-Guarde O">Jose M. Jimenez-Guarde O</name><affiliation><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Fernandez Delgado, Raul" sort="Fernandez Delgado, Raul" uniqKey="Fernandez Delgado R" first="Raul" last="Fernandez-Delgado">Raul Fernandez-Delgado</name><affiliation><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Fett, Craig" sort="Fett, Craig" uniqKey="Fett C" first="Craig" last="Fett">Craig Fett</name><affiliation><nlm:aff id="aff2">Department of Microbiology, University of Iowa, Iowa City, Iowa, USA</nlm:aff></affiliation></author><author><name sortKey="Casta O Rodriguez, Carlos" sort="Casta O Rodriguez, Carlos" uniqKey="Casta O Rodriguez C" first="Carlos" last="Casta O-Rodriguez">Carlos Casta O-Rodriguez</name><affiliation><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation><nlm:aff id="aff2">Department of Microbiology, University of Iowa, Iowa City, Iowa, USA</nlm:aff></affiliation></author><author><name sortKey="Enjuanes, Luis" sort="Enjuanes, Luis" uniqKey="Enjuanes L" first="Luis" last="Enjuanes">Luis Enjuanes</name><affiliation><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24198408</idno><idno type="pmc">3911641</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3911641</idno><idno type="RBID">PMC:3911641</idno><idno type="doi">10.1128/JVI.02576-13</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000C80</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000C80</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Inhibition of NF-κB-Mediated Inflammation in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice Increases Survival</title><author><name sortKey="Dediego, Marta L" sort="Dediego, Marta L" uniqKey="Dediego M" first="Marta L." last="Dediego">Marta L. Dediego</name><affiliation><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Nieto Torres, Jose L" sort="Nieto Torres, Jose L" uniqKey="Nieto Torres J" first="Jose L." last="Nieto-Torres">Jose L. Nieto-Torres</name><affiliation><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Regla Nava, Jose A" sort="Regla Nava, Jose A" uniqKey="Regla Nava J" first="Jose A." last="Regla-Nava">Jose A. Regla-Nava</name><affiliation><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Jimenez Guarde O, Jose M" sort="Jimenez Guarde O, Jose M" uniqKey="Jimenez Guarde O J" first="Jose M." last="Jimenez-Guarde O">Jose M. Jimenez-Guarde O</name><affiliation><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Fernandez Delgado, Raul" sort="Fernandez Delgado, Raul" uniqKey="Fernandez Delgado R" first="Raul" last="Fernandez-Delgado">Raul Fernandez-Delgado</name><affiliation><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Fett, Craig" sort="Fett, Craig" uniqKey="Fett C" first="Craig" last="Fett">Craig Fett</name><affiliation><nlm:aff id="aff2">Department of Microbiology, University of Iowa, Iowa City, Iowa, USA</nlm:aff></affiliation></author><author><name sortKey="Casta O Rodriguez, Carlos" sort="Casta O Rodriguez, Carlos" uniqKey="Casta O Rodriguez C" first="Carlos" last="Casta O-Rodriguez">Carlos Casta O-Rodriguez</name><affiliation><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation><nlm:aff id="aff2">Department of Microbiology, University of Iowa, Iowa City, Iowa, USA</nlm:aff></affiliation></author><author><name sortKey="Enjuanes, Luis" sort="Enjuanes, Luis" uniqKey="Enjuanes L" first="Luis" last="Enjuanes">Luis Enjuanes</name><affiliation><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</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="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of a respiratory disease that has a 10% mortality rate. We previously showed that SARS-CoV lacking the E gene (SARS-CoV-ΔE) is attenuated in several animal model systems. Here, we show that absence of the E protein resulted in reduced expression of proinflammatory cytokines, decreased numbers of neutrophils in lung infiltrates, diminished lung pathology, and increased mouse survival, suggesting that lung inflammation contributed to SARS-CoV virulence. Further, infection with SARS-CoV-ΔE resulted in decreased activation of NF-κB compared to levels for the wild-type virus. Most important, treatment with drugs that inhibited NF-κB activation led to a reduction in inflammation and lung pathology in both SARS-CoV-infected cultured cells and mice and significantly increased mouse survival after SARS-CoV infection. These data indicated that activation of the NF-κB signaling pathway represents a major contribution to the inflammation induced after SARS-CoV infection and that NF-κB inhibitors are promising antivirals in infections caused by SARS-CoV and potentially other pathogenic human coronaviruses.</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">24198408</article-id><article-id pub-id-type="pmc">3911641</article-id><article-id pub-id-type="publisher-id">02576-13</article-id><article-id pub-id-type="doi">10.1128/JVI.02576-13</article-id><article-categories><subj-group subj-group-type="heading"><subject>Pathogenesis and Immunity</subject></subj-group></article-categories><title-group><article-title>Inhibition of NF-κB-Mediated Inflammation in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice Increases Survival</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>DeDiego</surname><given-names>Marta L.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nieto-Torres</surname><given-names>Jose L.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Regla-Nava</surname><given-names>Jose A.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jimenez-Guardeño</surname><given-names>Jose M.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fernandez-Delgado</surname><given-names>Raul</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fett</surname><given-names>Craig</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Castaño-Rodriguez</surname><given-names>Carlos</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Perlman</surname><given-names>Stanley</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Enjuanes</surname><given-names>Luis</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><aff id="aff1"><label>a</label>Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</aff><aff id="aff2"><label>b</label>Department of Microbiology, University of Iowa, Iowa City, Iowa, USA</aff></contrib-group><author-notes><corresp id="cor1">Address correspondence to Luis Enjuanes, <email>L.Enjuanes@cnb.csic.es</email>.</corresp></author-notes><pub-date pub-type="ppub"><month>1</month><year>2014</year></pub-date><volume>88</volume><issue>2</issue><fpage>913</fpage><lpage>924</lpage><history><date date-type="received"><day>5</day><month>9</month><year>2013</year></date><date date-type="accepted"><day>29</day><month>10</month><year>2013</year></date></history><permissions><copyright-statement>Copyright © 2014, American Society for Microbiology. All Rights Reserved.</copyright-statement><copyright-year>2014</copyright-year><copyright-holder>American Society for Microbiology</copyright-holder></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zjv00214000913.pdf"></self-uri><abstract><p>Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of a respiratory disease that has a 10% mortality rate. We previously showed that SARS-CoV lacking the E gene (SARS-CoV-ΔE) is attenuated in several animal model systems. Here, we show that absence of the E protein resulted in reduced expression of proinflammatory cytokines, decreased numbers of neutrophils in lung infiltrates, diminished lung pathology, and increased mouse survival, suggesting that lung inflammation contributed to SARS-CoV virulence. Further, infection with SARS-CoV-ΔE resulted in decreased activation of NF-κB compared to levels for the wild-type virus. Most important, treatment with drugs that inhibited NF-κB activation led to a reduction in inflammation and lung pathology in both SARS-CoV-infected cultured cells and mice and significantly increased mouse survival after SARS-CoV infection. These data indicated that activation of the NF-κB signaling pathway represents a major contribution to the inflammation induced after SARS-CoV infection and that NF-κB inhibitors are promising antivirals in infections caused by SARS-CoV and potentially other pathogenic human coronaviruses.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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