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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Naturally Occurring Swine Influenza A Virus PB1-F2 Phenotypes That Contribute to Superinfection with Gram-Positive Respiratory Pathogens</title>
<author><name sortKey="Weeks Gorospe, Jenni N" sort="Weeks Gorospe, Jenni N" uniqKey="Weeks Gorospe J" first="Jenni N." last="Weeks-Gorospe">Jenni N. Weeks-Gorospe</name>
<affiliation><nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hurtig, Heather R" sort="Hurtig, Heather R" uniqKey="Hurtig H" first="Heather R." last="Hurtig">Heather R. Hurtig</name>
<affiliation><nlm:aff id="aff2">Division of Basic Biomedical Sciences, University of South Dakota, Vermillion, South Dakota, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Iverson, Amy R" sort="Iverson, Amy R" uniqKey="Iverson A" first="Amy R." last="Iverson">Amy R. Iverson</name>
<affiliation><nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schuneman, Margaret J" sort="Schuneman, Margaret J" uniqKey="Schuneman M" first="Margaret J." last="Schuneman">Margaret J. Schuneman</name>
<affiliation><nlm:aff id="aff2">Division of Basic Biomedical Sciences, University of South Dakota, Vermillion, South Dakota, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Webby, Richard J" sort="Webby, Richard J" uniqKey="Webby R" first="Richard J." last="Webby">Richard J. Webby</name>
<affiliation><nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mccullers, Jonathan A" sort="Mccullers, Jonathan A" uniqKey="Mccullers J" first="Jonathan A." last="Mccullers">Jonathan A. Mccullers</name>
<affiliation><nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Huber, Victor C" sort="Huber, Victor C" uniqKey="Huber V" first="Victor C." last="Huber">Victor C. Huber</name>
<affiliation><nlm:aff id="aff2">Division of Basic Biomedical Sciences, University of South Dakota, Vermillion, South Dakota, USA</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">22674997</idno>
<idno type="pmc">3416121</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3416121</idno>
<idno type="RBID">PMC:3416121</idno>
<idno type="doi">10.1128/JVI.00369-12</idno>
<date when="2012">2012</date>
<idno type="wicri:Area/Pmc/Corpus">000651</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000651</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Naturally Occurring Swine Influenza A Virus PB1-F2 Phenotypes That Contribute to Superinfection with Gram-Positive Respiratory Pathogens</title>
<author><name sortKey="Weeks Gorospe, Jenni N" sort="Weeks Gorospe, Jenni N" uniqKey="Weeks Gorospe J" first="Jenni N." last="Weeks-Gorospe">Jenni N. Weeks-Gorospe</name>
<affiliation><nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hurtig, Heather R" sort="Hurtig, Heather R" uniqKey="Hurtig H" first="Heather R." last="Hurtig">Heather R. Hurtig</name>
<affiliation><nlm:aff id="aff2">Division of Basic Biomedical Sciences, University of South Dakota, Vermillion, South Dakota, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Iverson, Amy R" sort="Iverson, Amy R" uniqKey="Iverson A" first="Amy R." last="Iverson">Amy R. Iverson</name>
<affiliation><nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schuneman, Margaret J" sort="Schuneman, Margaret J" uniqKey="Schuneman M" first="Margaret J." last="Schuneman">Margaret J. Schuneman</name>
<affiliation><nlm:aff id="aff2">Division of Basic Biomedical Sciences, University of South Dakota, Vermillion, South Dakota, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Webby, Richard J" sort="Webby, Richard J" uniqKey="Webby R" first="Richard J." last="Webby">Richard J. Webby</name>
<affiliation><nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mccullers, Jonathan A" sort="Mccullers, Jonathan A" uniqKey="Mccullers J" first="Jonathan A." last="Mccullers">Jonathan A. Mccullers</name>
<affiliation><nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Huber, Victor C" sort="Huber, Victor C" uniqKey="Huber V" first="Victor C." last="Huber">Victor C. Huber</name>
<affiliation><nlm:aff id="aff2">Division of Basic Biomedical Sciences, University of South Dakota, Vermillion, South Dakota, USA</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>A combination of viral, bacterial, and host factors contributes to the severity and overall mortality associated with influenza virus-bacterium superinfections. To date, the virulence associated with the recently identified influenza virus protein PB1-F2 has been largely defined using models of primary influenza virus infection, with only limited assessment in models of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
superinfection. Specifically, these studies have incorporated isogenic viruses that differ in the PB1-F2 expressed, but there is still knowledge to be gained from evaluation of natural variants derived from a nonhuman host species (swine). Using this rationale, we developed the hypothesis that naturally occurring viruses expressing variants of genes, like the PB1-F2 gene, can be associated with the severity of secondary bacterial infections. To test this hypothesis, we selected viruses expressing variants in PB1-F2 and evaluated outcomes from superinfection with three distinct Gram-positive respiratory pathogens: <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
, <named-content content-type="genus-species">Staphylococcus aureus</named-content>
, and <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
. Our results demonstrate that the amino acid residues 62L, 66S, 75R, 79R, and 82L, previously proposed as molecular signatures of PB1-F2 virulence for influenza viruses in the setting of bacterial superinfection, are broadly associated with enhanced pathogenicity in swine in a bacterium-specific manner. Furthermore, truncated PB1-F2 proteins can preferentially increase mortality when associated with <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
superinfection. These findings support efforts to increase influenza virus surveillance to consider viral genotypes that could be used to predict increased severity of superinfections with specific Gram-positive respiratory pathogens.</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">22674997</article-id>
<article-id pub-id-type="pmc">3416121</article-id>
<article-id pub-id-type="publisher-id">00369-12</article-id>
<article-id pub-id-type="doi">10.1128/JVI.00369-12</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Pathogenesis and Immunity</subject>
</subj-group>
</article-categories>
<title-group><article-title>Naturally Occurring Swine Influenza A Virus PB1-F2 Phenotypes That Contribute to Superinfection with Gram-Positive Respiratory Pathogens</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Weeks-Gorospe</surname>
<given-names>Jenni N.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hurtig</surname>
<given-names>Heather R.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Iverson</surname>
<given-names>Amy R.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schuneman</surname>
<given-names>Margaret J.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Webby</surname>
<given-names>Richard J.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>McCullers</surname>
<given-names>Jonathan A.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Huber</surname>
<given-names>Victor C.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<aff id="aff1"><label>a</label>
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</aff>
<aff id="aff2"><label>b</label>
Division of Basic Biomedical Sciences, University of South Dakota, Vermillion, South Dakota, USA</aff>
</contrib-group>
<author-notes><corresp>Address correspondence to Victor C. Huber, <email>victor.huber@usd.edu</email>
.</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>9</month>
<year>2012</year>
</pub-date>
<volume>86</volume>
<issue>17</issue>
<fpage>9035</fpage>
<lpage>9043</lpage>
<history><date date-type="received"><day>13</day>
<month>2</month>
<year>2012</year>
</date>
<date date-type="accepted"><day>30</day>
<month>5</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="zjv01712009035.pdf"></self-uri>
<abstract><p>A combination of viral, bacterial, and host factors contributes to the severity and overall mortality associated with influenza virus-bacterium superinfections. To date, the virulence associated with the recently identified influenza virus protein PB1-F2 has been largely defined using models of primary influenza virus infection, with only limited assessment in models of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
superinfection. Specifically, these studies have incorporated isogenic viruses that differ in the PB1-F2 expressed, but there is still knowledge to be gained from evaluation of natural variants derived from a nonhuman host species (swine). Using this rationale, we developed the hypothesis that naturally occurring viruses expressing variants of genes, like the PB1-F2 gene, can be associated with the severity of secondary bacterial infections. To test this hypothesis, we selected viruses expressing variants in PB1-F2 and evaluated outcomes from superinfection with three distinct Gram-positive respiratory pathogens: <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
, <named-content content-type="genus-species">Staphylococcus aureus</named-content>
, and <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
. Our results demonstrate that the amino acid residues 62L, 66S, 75R, 79R, and 82L, previously proposed as molecular signatures of PB1-F2 virulence for influenza viruses in the setting of bacterial superinfection, are broadly associated with enhanced pathogenicity in swine in a bacterium-specific manner. Furthermore, truncated PB1-F2 proteins can preferentially increase mortality when associated with <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
superinfection. These findings support efforts to increase influenza virus surveillance to consider viral genotypes that could be used to predict increased severity of superinfections with specific Gram-positive respiratory pathogens.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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