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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Macaque Proteome Response to Highly Pathogenic Avian Influenza and 1918 Reassortant Influenza Virus Infections<xref ref-type="fn" rid="fn4">▿</xref>
<xref ref-type="fn" rid="fn1">†</xref>
</title>
<author><name sortKey="Brown, Joseph N" sort="Brown, Joseph N" uniqKey="Brown J" first="Joseph N." last="Brown">Joseph N. Brown</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Palermo, Robert E" sort="Palermo, Robert E" uniqKey="Palermo R" first="Robert E." last="Palermo">Robert E. Palermo</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Baskin, Carole R" sort="Baskin, Carole R" uniqKey="Baskin C" first="Carole R." last="Baskin">Carole R. Baskin</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gritsenko, Marina" sort="Gritsenko, Marina" uniqKey="Gritsenko M" first="Marina" last="Gritsenko">Marina Gritsenko</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sabourin, Patrick J" sort="Sabourin, Patrick J" uniqKey="Sabourin P" first="Patrick J." last="Sabourin">Patrick J. Sabourin</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Long, James P" sort="Long, James P" uniqKey="Long J" first="James P." last="Long">James P. Long</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sabourin, Carol L" sort="Sabourin, Carol L" uniqKey="Sabourin C" first="Carol L." last="Sabourin">Carol L. Sabourin</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bielefeldt Ohmann, Helle" sort="Bielefeldt Ohmann, Helle" uniqKey="Bielefeldt Ohmann H" first="Helle" last="Bielefeldt-Ohmann">Helle Bielefeldt-Ohmann</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>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Albrecht, Randy" sort="Albrecht, Randy" uniqKey="Albrecht R" first="Randy" last="Albrecht">Randy Albrecht</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>
<author><name sortKey="Jacobs, Jon M" sort="Jacobs, Jon M" uniqKey="Jacobs J" first="Jon M." last="Jacobs">Jon M. Jacobs</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Smith, Richard D" sort="Smith, Richard D" uniqKey="Smith R" first="Richard D." last="Smith">Richard D. Smith</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>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">20844032</idno>
<idno type="pmc">2977874</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2977874</idno>
<idno type="RBID">PMC:2977874</idno>
<idno type="doi">10.1128/JVI.01129-10</idno>
<date when="2010">2010</date>
<idno type="wicri:Area/Pmc/Corpus">000723</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000723</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Macaque Proteome Response to Highly Pathogenic Avian Influenza and 1918 Reassortant Influenza Virus Infections<xref ref-type="fn" rid="fn4">▿</xref>
<xref ref-type="fn" rid="fn1">†</xref>
</title>
<author><name sortKey="Brown, Joseph N" sort="Brown, Joseph N" uniqKey="Brown J" first="Joseph N." last="Brown">Joseph N. Brown</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Palermo, Robert E" sort="Palermo, Robert E" uniqKey="Palermo R" first="Robert E." last="Palermo">Robert E. Palermo</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Baskin, Carole R" sort="Baskin, Carole R" uniqKey="Baskin C" first="Carole R." last="Baskin">Carole R. Baskin</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gritsenko, Marina" sort="Gritsenko, Marina" uniqKey="Gritsenko M" first="Marina" last="Gritsenko">Marina Gritsenko</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sabourin, Patrick J" sort="Sabourin, Patrick J" uniqKey="Sabourin P" first="Patrick J." last="Sabourin">Patrick J. Sabourin</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Long, James P" sort="Long, James P" uniqKey="Long J" first="James P." last="Long">James P. Long</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sabourin, Carol L" sort="Sabourin, Carol L" uniqKey="Sabourin C" first="Carol L." last="Sabourin">Carol L. Sabourin</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bielefeldt Ohmann, Helle" sort="Bielefeldt Ohmann, Helle" uniqKey="Bielefeldt Ohmann H" first="Helle" last="Bielefeldt-Ohmann">Helle Bielefeldt-Ohmann</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>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Albrecht, Randy" sort="Albrecht, Randy" uniqKey="Albrecht R" first="Randy" last="Albrecht">Randy Albrecht</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>
<author><name sortKey="Jacobs, Jon M" sort="Jacobs, Jon M" uniqKey="Jacobs J" first="Jon M." last="Jacobs">Jon M. Jacobs</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Smith, Richard D" sort="Smith, Richard D" uniqKey="Smith R" first="Richard D." last="Smith">Richard D. Smith</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>
</analytic>
<series><title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
<idno type="eISSN">1098-5514</idno>
<imprint><date when="2010">2010</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
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<profileDesc><textClass></textClass>
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</teiHeader>
<front><div type="abstract" xml:lang="en"><p>The host proteome response and molecular mechanisms that drive disease <italic>in vivo</italic>
during infection by a human isolate of the highly pathogenic avian influenza virus (HPAI) and 1918 pandemic influenza virus remain poorly understood. This study presents a comprehensive characterization of the proteome response in cynomolgus macaque (<italic>Macaca fascicularis</italic>
) lung tissue over 7 days of infection with HPAI (the most virulent), a reassortant virus containing 1918 hemagglutinin and neuraminidase surface proteins (intermediate virulence), or a human seasonal strain (least virulent). A high-sensitivity two-dimensional liquid chromatography-tandem mass spectroscopy strategy and functional network analysis were implemented to gain insight into response pathways activated in macaques during influenza virus infection. A macaque protein database was assembled and used in the identification of 35,239 unique peptide sequences corresponding to approximately 4,259 proteins. Quantitative analysis identified an increase in expression of 400 proteins during viral infection. The abundance levels of a subset of these 400 proteins produced strong correlations with disease progression observed in the macaques, distinguishing a “core” response to viral infection from a “high” response specific to severe disease. Proteome expression profiles revealed distinct temporal response kinetics between viral strains, with HPAI inducing the most rapid response. While proteins involved in the immune response, metabolism, and transport were increased rapidly in the lung by HPAI, the other viruses produced a delayed response, characterized by an increase in proteins involved in oxidative phosphorylation, RNA processing, and translation. Proteomic results were integrated with previous genomic and pathological analysis to characterize the dynamic nature of the influenza virus infection process.</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="publisher-id">jvirol</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 (ASM)</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">20844032</article-id>
<article-id pub-id-type="pmc">2977874</article-id>
<article-id pub-id-type="publisher-id">1129-10</article-id>
<article-id pub-id-type="doi">10.1128/JVI.01129-10</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Pathogenesis and Immunity</subject>
</subj-group>
</article-categories>
<title-group><article-title>Macaque Proteome Response to Highly Pathogenic Avian Influenza and 1918 Reassortant Influenza Virus Infections<xref ref-type="fn" rid="fn4">▿</xref>
<xref ref-type="fn" rid="fn1">†</xref>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Brown</surname>
<given-names>Joseph N.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Palermo</surname>
<given-names>Robert E.</given-names>
</name>
<xref ref-type="aff" rid="aff1">2</xref>
<xref ref-type="aff" rid="aff1">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Baskin</surname>
<given-names>Carole R.</given-names>
</name>
<xref ref-type="aff" rid="aff1">2</xref>
<xref ref-type="aff" rid="aff1">3</xref>
<xref ref-type="fn" rid="fn2">‡</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gritsenko</surname>
<given-names>Marina</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sabourin</surname>
<given-names>Patrick J.</given-names>
</name>
<xref ref-type="aff" rid="aff1">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Long</surname>
<given-names>James P.</given-names>
</name>
<xref ref-type="aff" rid="aff1">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sabourin</surname>
<given-names>Carol L.</given-names>
</name>
<xref ref-type="aff" rid="aff1">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bielefeldt-Ohmann</surname>
<given-names>Helle</given-names>
</name>
<xref ref-type="aff" rid="aff1">5</xref>
<xref ref-type="fn" rid="fn3">§</xref>
</contrib>
<contrib contrib-type="author"><name><surname>García-Sastre</surname>
<given-names>Adolfo</given-names>
</name>
<xref ref-type="aff" rid="aff1">6</xref>
<xref ref-type="aff" rid="aff1">7</xref>
<xref ref-type="aff" rid="aff1">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Albrecht</surname>
<given-names>Randy</given-names>
</name>
<xref ref-type="aff" rid="aff1">6</xref>
<xref ref-type="aff" rid="aff1">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tumpey</surname>
<given-names>Terrence M.</given-names>
</name>
<xref ref-type="aff" rid="aff1">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jacobs</surname>
<given-names>Jon M.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Smith</surname>
<given-names>Richard D.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Katze</surname>
<given-names>Michael G.</given-names>
</name>
<xref ref-type="aff" rid="aff1">2</xref>
<xref ref-type="aff" rid="aff1">3</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
</contrib-group>
<aff id="aff1">Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratories, Richland, Washington 99352,<label>1</label>
Department of Microbiology,<label>2</label>
Washington National Primate Research Center, University of Washington, Seattle, Washington 98195,<label>3</label>
Battelle Biomedical Research Center, West Jefferson, Ohio 43201,<label>4</label>
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado 80523,<label>5</label>
Departments of Microbiology,<label>6</label>
Medicine, Division of Infectious Diseases,<label>7</label>
Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, New York 10029,<label>8</label>
Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia 30333<label>9</label>
</aff>
<author-notes><corresp id="cor1"><label>*</label>
Corresponding author. Mailing address: Department of Microbiology, Washington National Primate Research Center, Box 358070, Seattle, WA 98195. Phone: (206) 732-6135. Fax: (206) 732-6056. E-mail: <email>honey@u.washington.edu</email>
</corresp>
<fn id="fn2"><label>‡</label>
<p>Present address: Science Foundation Arizona, 400 East Van Buren Street, Phoenix, AZ 85004.</p>
</fn>
<fn id="fn3"><label>§</label>
<p>Present address: University of Queensland, St. Lucia, Queensland 4072, Australia.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>11</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="epub"><day>15</day>
<month>9</month>
<year>2010</year>
</pub-date>
<volume>84</volume>
<issue>22</issue>
<fpage>12058</fpage>
<lpage>12068</lpage>
<history><date date-type="received"><day>26</day>
<month>5</month>
<year>2010</year>
</date>
<date date-type="accepted"><day>3</day>
<month>9</month>
<year>2010</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2010, American Society for Microbiology</copyright-statement>
<copyright-year>2010</copyright-year>
</permissions>
<self-uri xlink:title="pdf" xlink:href="zjv02210012058.pdf"></self-uri>
<abstract><p>The host proteome response and molecular mechanisms that drive disease <italic>in vivo</italic>
during infection by a human isolate of the highly pathogenic avian influenza virus (HPAI) and 1918 pandemic influenza virus remain poorly understood. This study presents a comprehensive characterization of the proteome response in cynomolgus macaque (<italic>Macaca fascicularis</italic>
) lung tissue over 7 days of infection with HPAI (the most virulent), a reassortant virus containing 1918 hemagglutinin and neuraminidase surface proteins (intermediate virulence), or a human seasonal strain (least virulent). A high-sensitivity two-dimensional liquid chromatography-tandem mass spectroscopy strategy and functional network analysis were implemented to gain insight into response pathways activated in macaques during influenza virus infection. A macaque protein database was assembled and used in the identification of 35,239 unique peptide sequences corresponding to approximately 4,259 proteins. Quantitative analysis identified an increase in expression of 400 proteins during viral infection. The abundance levels of a subset of these 400 proteins produced strong correlations with disease progression observed in the macaques, distinguishing a “core” response to viral infection from a “high” response specific to severe disease. Proteome expression profiles revealed distinct temporal response kinetics between viral strains, with HPAI inducing the most rapid response. While proteins involved in the immune response, metabolism, and transport were increased rapidly in the lung by HPAI, the other viruses produced a delayed response, characterized by an increase in proteins involved in oxidative phosphorylation, RNA processing, and translation. Proteomic results were integrated with previous genomic and pathological analysis to characterize the dynamic nature of the influenza virus infection process.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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