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<title xml:lang="en">Global Host Immune Response: Pathogenesis and Transcriptional Profiling of Type A Influenza Viruses Expressing the Hemagglutinin and Neuraminidase Genes from the 1918 Pandemic Virus</title>
<author>
<name sortKey="Kash, John C" sort="Kash, John C" uniqKey="Kash J" first="John C." last="Kash">John C. Kash</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
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<author>
<name sortKey="Basler, Christopher F" sort="Basler, Christopher F" uniqKey="Basler C" first="Christopher F." last="Basler">Christopher F. Basler</name>
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<author>
<name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name>
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<name sortKey="Carter, Victoria" sort="Carter, Victoria" uniqKey="Carter V" first="Victoria" last="Carter">Victoria Carter</name>
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<name sortKey="Billharz, Rosalind" sort="Billharz, Rosalind" uniqKey="Billharz R" first="Rosalind" last="Billharz">Rosalind Billharz</name>
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<name sortKey="Swayne, David E" sort="Swayne, David E" uniqKey="Swayne D" first="David E." last="Swayne">David E. Swayne</name>
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<name sortKey="Przygodzki, Ronald M" sort="Przygodzki, Ronald M" uniqKey="Przygodzki R" first="Ronald M." last="Przygodzki">Ronald M. Przygodzki</name>
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<name sortKey="Taubenberger, Jeffery K" sort="Taubenberger, Jeffery K" uniqKey="Taubenberger J" first="Jeffery K." last="Taubenberger">Jeffery K. Taubenberger</name>
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<name sortKey="Katze, Michael G" sort="Katze, Michael G" uniqKey="Katze M" first="Michael G." last="Katze">Michael G. Katze</name>
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<name sortKey="Tumpey, Terrence M" sort="Tumpey, Terrence M" uniqKey="Tumpey T" first="Terrence M." last="Tumpey">Terrence M. Tumpey</name>
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<idno type="doi">10.1128/JVI.78.17.9499-9511.2004</idno>
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<title xml:lang="en" level="a" type="main">Global Host Immune Response: Pathogenesis and Transcriptional Profiling of Type A Influenza Viruses Expressing the Hemagglutinin and Neuraminidase Genes from the 1918 Pandemic Virus</title>
<author>
<name sortKey="Kash, John C" sort="Kash, John C" uniqKey="Kash J" first="John C." last="Kash">John C. Kash</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Basler, Christopher F" sort="Basler, Christopher F" uniqKey="Basler C" first="Christopher F." last="Basler">Christopher F. Basler</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Carter, Victoria" sort="Carter, Victoria" uniqKey="Carter V" first="Victoria" last="Carter">Victoria Carter</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Billharz, Rosalind" sort="Billharz, Rosalind" uniqKey="Billharz R" first="Rosalind" last="Billharz">Rosalind Billharz</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Swayne, David E" sort="Swayne, David E" uniqKey="Swayne D" first="David E." last="Swayne">David E. Swayne</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
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<author>
<name sortKey="Przygodzki, Ronald M" sort="Przygodzki, Ronald M" uniqKey="Przygodzki R" first="Ronald M." last="Przygodzki">Ronald M. Przygodzki</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Taubenberger, Jeffery K" sort="Taubenberger, Jeffery K" uniqKey="Taubenberger J" first="Jeffery K." last="Taubenberger">Jeffery K. Taubenberger</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Katze, Michael G" sort="Katze, Michael G" uniqKey="Katze M" first="Michael G." last="Katze">Michael G. Katze</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Tumpey, Terrence M" sort="Tumpey, Terrence M" uniqKey="Tumpey T" first="Terrence M." last="Tumpey">Terrence M. Tumpey</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
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<series>
<title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
<idno type="eISSN">1098-5514</idno>
<imprint>
<date when="2004">2004</date>
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<front>
<div type="abstract" xml:lang="en">
<p>To understand more fully the molecular events associated with highly virulent or attenuated influenza virus infections, we have studied the effects of expression of the 1918 hemagglutinin (HA) and neuraminidase (NA) genes during viral infection in mice under biosafety level 3 (agricultural) conditions. Using histopathology and cDNA microarrays, we examined the consequences of expression of the HA and NA genes of the 1918 pandemic virus in a recombinant influenza A/WSN/33 virus compared to parental A/WSN/33 virus and to an attenuated virus expressing the HA and NA genes from A/New Caledonia/20/99. The 1918 HA/NA:WSN and WSN recombinant viruses were highly lethal for mice and displayed severe lung pathology in comparison to the nonlethal New Caledonia HA/NA:WSN recombinant virus. Expression microarray analysis performed on lung tissues isolated from the infected animals showed activation of many genes involved in the inflammatory response, including cytokine, apoptosis, and lymphocyte genes that were common to all three infection groups. However, consistent with the histopathology studies, the WSN and 1918 HA/NA:WSN recombinant viruses showed increased up-regulation of genes associated with activated T cells and macrophages, as well as genes involved in apoptosis, tissue injury, and oxidative damage that were not observed in the New Caledonia HA/NA:WSN recombinant virus-infected mice. These studies document clear differences in gene expression profiles that were correlated with pulmonary disease pathology induced by virulent and attenuated influenza virus infections.</p>
</div>
</front>
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<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="publisher-id">jvi</journal-id>
<journal-title>Journal of Virology</journal-title>
<issn pub-type="ppub">0022-538X</issn>
<issn pub-type="epub">1098-5514</issn>
<publisher>
<publisher-name>American Society for Microbiology</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">15308742</article-id>
<article-id pub-id-type="pmc">506954</article-id>
<article-id pub-id-type="publisher-id">2358-03</article-id>
<article-id pub-id-type="doi">10.1128/JVI.78.17.9499-9511.2004</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Virus-Cell Interactions</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Global Host Immune Response: Pathogenesis and Transcriptional Profiling of Type A Influenza Viruses Expressing the Hemagglutinin and Neuraminidase Genes from the 1918 Pandemic Virus</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Kash</surname>
<given-names>John C.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Basler</surname>
<given-names>Christopher F.</given-names>
</name>
<xref ref-type="aff" rid="aff1">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>García-Sastre</surname>
<given-names>Adolfo</given-names>
</name>
<xref ref-type="aff" rid="aff1">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Carter</surname>
<given-names>Victoria</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Billharz</surname>
<given-names>Rosalind</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Swayne</surname>
<given-names>David E.</given-names>
</name>
<xref ref-type="aff" rid="aff1">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Przygodzki</surname>
<given-names>Ronald M.</given-names>
</name>
<xref ref-type="aff" rid="aff1">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Taubenberger</surname>
<given-names>Jeffery K.</given-names>
</name>
<xref ref-type="aff" rid="aff1">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Katze</surname>
<given-names>Michael G.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff1">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tumpey</surname>
<given-names>Terrence M.</given-names>
</name>
<xref ref-type="aff" rid="aff1">3</xref>
<xref ref-type="fn" rid="fn1"></xref>
</contrib>
</contrib-group>
<aff id="aff1">Department of Microbiology, School of Medicine,
<label>1</label>
Washington National Primate Research Center, University of Washington, Seattle, Washington,
<label>5</label>
Department of Microbiology, Mount Sinai School of Medicine, New York, New York,
<label>2</label>
Southeast Poultry Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Athens, Georgia,
<label>3</label>
Division of Molecular Pathology, Department of Cellular Pathology and Genetics, Armed Forces Institute of Pathology, Washington, D.C.
<label>4</label>
</aff>
<author-notes>
<fn id="cor1">
<label>*</label>
<p>Corresponding author. Mailing address: Department of Microbiology, University of Washington School of Medicine, Box 358070, Seattle, WA 98195-8070. Phone: (206) 732-6158. Fax: (206) 732-6055. E-mail:
<email>jkash@u.washington.edu</email>
.</p>
</fn>
<fn id="fn1">
<label></label>
<p>Present address: Influenza Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub">
<month>9</month>
<year>2004</year>
</pub-date>
<volume>78</volume>
<issue>17</issue>
<fpage>9499</fpage>
<lpage>9511</lpage>
<history>
<date date-type="received">
<day>10</day>
<month>11</month>
<year>2003</year>
</date>
<date date-type="accepted">
<day>2</day>
<month>4</month>
<year>2004</year>
</date>
</history>
<copyright-statement>Copyright © 2004, American Society for Microbiology</copyright-statement>
<copyright-year>2004</copyright-year>
<abstract>
<p>To understand more fully the molecular events associated with highly virulent or attenuated influenza virus infections, we have studied the effects of expression of the 1918 hemagglutinin (HA) and neuraminidase (NA) genes during viral infection in mice under biosafety level 3 (agricultural) conditions. Using histopathology and cDNA microarrays, we examined the consequences of expression of the HA and NA genes of the 1918 pandemic virus in a recombinant influenza A/WSN/33 virus compared to parental A/WSN/33 virus and to an attenuated virus expressing the HA and NA genes from A/New Caledonia/20/99. The 1918 HA/NA:WSN and WSN recombinant viruses were highly lethal for mice and displayed severe lung pathology in comparison to the nonlethal New Caledonia HA/NA:WSN recombinant virus. Expression microarray analysis performed on lung tissues isolated from the infected animals showed activation of many genes involved in the inflammatory response, including cytokine, apoptosis, and lymphocyte genes that were common to all three infection groups. However, consistent with the histopathology studies, the WSN and 1918 HA/NA:WSN recombinant viruses showed increased up-regulation of genes associated with activated T cells and macrophages, as well as genes involved in apoptosis, tissue injury, and oxidative damage that were not observed in the New Caledonia HA/NA:WSN recombinant virus-infected mice. These studies document clear differences in gene expression profiles that were correlated with pulmonary disease pathology induced by virulent and attenuated influenza virus infections.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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