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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Strain-dependent effects of PB1-F2 of triple-reassortant H3N2 influenza viruses in swine</title>
<author><name sortKey="Pena, Lindomar" sort="Pena, Lindomar" uniqKey="Pena L" first="Lindomar" last="Pena">Lindomar Pena</name>
<affiliation><nlm:aff id="aff1">Department of Veterinary Medicine, University of Maryland, College Park, MD, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Virginia–Maryland Regional College of Veterinary Medicine, College Park, MD, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vincent, Amy L" sort="Vincent, Amy L" uniqKey="Vincent A" first="Amy L." last="Vincent">Amy L. Vincent</name>
<affiliation><nlm:aff id="aff3">Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Loving, Crystal L" sort="Loving, Crystal L" uniqKey="Loving C" first="Crystal L." last="Loving">Crystal L. Loving</name>
<affiliation><nlm:aff id="aff3">Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Henningson, Jamie N" sort="Henningson, Jamie N" uniqKey="Henningson J" first="Jamie N." last="Henningson">Jamie N. Henningson</name>
<affiliation><nlm:aff id="aff3">Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lager, Kelly M" sort="Lager, Kelly M" uniqKey="Lager K" first="Kelly M." last="Lager">Kelly M. Lager</name>
<affiliation><nlm:aff id="aff3">Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Li, Weizhong" sort="Li, Weizhong" uniqKey="Li W" first="Weizhong" last="Li">Weizhong Li</name>
<affiliation><nlm:aff id="aff1">Department of Veterinary Medicine, University of Maryland, College Park, MD, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Virginia–Maryland Regional College of Veterinary Medicine, College Park, MD, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Perez, Daniel R" sort="Perez, Daniel R" uniqKey="Perez D" first="Daniel R." last="Perez">Daniel R. Perez</name>
<affiliation><nlm:aff id="aff1">Department of Veterinary Medicine, University of Maryland, College Park, MD, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Virginia–Maryland Regional College of Veterinary Medicine, College Park, MD, USA</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">22815274</idno>
<idno type="pmc">3541787</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541787</idno>
<idno type="RBID">PMC:3541787</idno>
<idno type="doi">10.1099/vir.0.045005-0</idno>
<date when="2012">2012</date>
<idno type="wicri:Area/Pmc/Corpus">000626</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Strain-dependent effects of PB1-F2 of triple-reassortant H3N2 influenza viruses in swine</title>
<author><name sortKey="Pena, Lindomar" sort="Pena, Lindomar" uniqKey="Pena L" first="Lindomar" last="Pena">Lindomar Pena</name>
<affiliation><nlm:aff id="aff1">Department of Veterinary Medicine, University of Maryland, College Park, MD, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Virginia–Maryland Regional College of Veterinary Medicine, College Park, MD, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vincent, Amy L" sort="Vincent, Amy L" uniqKey="Vincent A" first="Amy L." last="Vincent">Amy L. Vincent</name>
<affiliation><nlm:aff id="aff3">Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Loving, Crystal L" sort="Loving, Crystal L" uniqKey="Loving C" first="Crystal L." last="Loving">Crystal L. Loving</name>
<affiliation><nlm:aff id="aff3">Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Henningson, Jamie N" sort="Henningson, Jamie N" uniqKey="Henningson J" first="Jamie N." last="Henningson">Jamie N. Henningson</name>
<affiliation><nlm:aff id="aff3">Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lager, Kelly M" sort="Lager, Kelly M" uniqKey="Lager K" first="Kelly M." last="Lager">Kelly M. Lager</name>
<affiliation><nlm:aff id="aff3">Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Li, Weizhong" sort="Li, Weizhong" uniqKey="Li W" first="Weizhong" last="Li">Weizhong Li</name>
<affiliation><nlm:aff id="aff1">Department of Veterinary Medicine, University of Maryland, College Park, MD, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Virginia–Maryland Regional College of Veterinary Medicine, College Park, MD, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Perez, Daniel R" sort="Perez, Daniel R" uniqKey="Perez D" first="Daniel R." last="Perez">Daniel R. Perez</name>
<affiliation><nlm:aff id="aff1">Department of Veterinary Medicine, University of Maryland, College Park, MD, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Virginia–Maryland Regional College of Veterinary Medicine, College Park, MD, USA</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">The Journal of General Virology</title>
<idno type="ISSN">0022-1317</idno>
<idno type="eISSN">1465-2099</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
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<front><div type="abstract" xml:lang="en"><p>The PB1-F2 protein of the influenza A viruses (IAVs) can act as a virulence factor in mice. Its contribution to the virulence of IAV in swine, however, remains largely unexplored. In this study, we chose two genetically related H3N2 triple-reassortant IAVs to assess the impact of PB1-F2 in virus replication and virulence in pigs. Using reverse genetics, we disrupted the PB1-F2 ORF of A/swine/Wisconsin/14094/99 (H3N2) (Sw/99) and A/turkey/Ohio/313053/04 (H3N2) (Ty/04). Removing the PB1-F2 ORF led to increased expression of PB1-N40 in a strain-dependent manner. Ablation of the PB1-F2 ORF (or incorporation of the N66S mutation in the PB1-F2 ORF, Sw/99 N66S) affected the replication in porcine alveolar macrophages of only the Sw/99 KO (PB1-F2 knockout) and Sw/99 N66S variants. The Ty/04 KO strain showed decreased virus replication in swine respiratory explants, whereas no such effect was observed in Sw/99 KO, compared with the wild-type (WT) counterparts. In pigs, PB1-F2 did not affect virus shedding or viral load in the lungs for any of these strains. Upon necropsy, PB1-F2 had no effect on the lung pathology caused by Sw/99 variants. Interestingly, the Ty/04 KO-infected pigs showed significantly increased lung pathology at 3 days post-infection compared with pigs infected with the Ty/04 WT strain. In addition, the pulmonary levels of interleukin (IL)-6, IL-8 and gamma interferon were regulated differentially by the expression of PB1-F2. Taken together, these results indicate that PB1-F2 modulates virus replication, virulence and innate immune responses in pigs in a strain-dependent fashion.</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 Gen Virol</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Gen. Virol</journal-id>
<journal-id journal-id-type="publisher-id">JGV</journal-id>
<journal-id journal-id-type="hwp">vir</journal-id>
<journal-title-group><journal-title>The Journal of General Virology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0022-1317</issn>
<issn pub-type="epub">1465-2099</issn>
<publisher><publisher-name>Society for General Microbiology</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22815274</article-id>
<article-id pub-id-type="pmc">3541787</article-id>
<article-id pub-id-type="publisher-id">045005</article-id>
<article-id pub-id-type="doi">10.1099/vir.0.045005-0</article-id>
<article-categories><subj-group subj-group-type="article-type"><subject>Standard</subject>
</subj-group>
<subj-group subj-group-type="heading"><subject>Animal</subject>
<subj-group subj-group-type="heading"><subject>RNA viruses</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Strain-dependent effects of PB1-F2 of triple-reassortant H3N2 influenza viruses in swine</article-title>
<alt-title alt-title-type="recto-page-foot"><ext-link ext-link-type="uri" xlink:href="http://vir.sgmjournals.org">http://vir.sgmjournals.org</ext-link>
</alt-title>
<alt-title alt-title-type="verso-running-head">L. Pena and others</alt-title>
<alt-title alt-title-type="recto-running-head">Effects of influenza PB1-F2 in pigs</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Pena</surname>
<given-names>Lindomar</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Vincent</surname>
<given-names>Amy L.</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Loving</surname>
<given-names>Crystal L.</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Henningson</surname>
<given-names>Jamie N.</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lager</surname>
<given-names>Kelly M.</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Li</surname>
<given-names>Weizhong</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Perez</surname>
<given-names>Daniel R.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<aff id="aff1"><label>1</label>
Department of Veterinary Medicine, University of Maryland, College Park, MD, USA</aff>
<aff id="aff2"><label>2</label>
Virginia–Maryland Regional College of Veterinary Medicine, College Park, MD, USA</aff>
<aff id="aff3"><label>3</label>
Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA</aff>
</contrib-group>
<author-notes><corresp id="cor1"><bold>Correspondence</bold>
Daniel R. Perez <email xlink:href="dperez1@umd.edu">dperez1@umd.edu</email>
Amy L. Vincent <email xlink:href="Amy.Vincent@ars.usda.gov">Amy.Vincent@ars.usda.gov</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>10</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>1</day>
<month>10</month>
<year>2013</year>
</pub-date>
<pmc-comment> PMC Release delay is 12 months and 0 days and was based on the
. </pmc-comment>
<volume>93</volume>
<issue>Pt 10</issue>
<fpage>2204</fpage>
<lpage>2214</lpage>
<history><date date-type="received"><day>06</day>
<month>6</month>
<year>2012</year>
</date>
<date date-type="accepted"><day>17</day>
<month>7</month>
<year>2012</year>
</date>
</history>
<permissions><copyright-statement>© 2012 SGM</copyright-statement>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="2204_vir045005.pdf"></self-uri>
<abstract><p>The PB1-F2 protein of the influenza A viruses (IAVs) can act as a virulence factor in mice. Its contribution to the virulence of IAV in swine, however, remains largely unexplored. In this study, we chose two genetically related H3N2 triple-reassortant IAVs to assess the impact of PB1-F2 in virus replication and virulence in pigs. Using reverse genetics, we disrupted the PB1-F2 ORF of A/swine/Wisconsin/14094/99 (H3N2) (Sw/99) and A/turkey/Ohio/313053/04 (H3N2) (Ty/04). Removing the PB1-F2 ORF led to increased expression of PB1-N40 in a strain-dependent manner. Ablation of the PB1-F2 ORF (or incorporation of the N66S mutation in the PB1-F2 ORF, Sw/99 N66S) affected the replication in porcine alveolar macrophages of only the Sw/99 KO (PB1-F2 knockout) and Sw/99 N66S variants. The Ty/04 KO strain showed decreased virus replication in swine respiratory explants, whereas no such effect was observed in Sw/99 KO, compared with the wild-type (WT) counterparts. In pigs, PB1-F2 did not affect virus shedding or viral load in the lungs for any of these strains. Upon necropsy, PB1-F2 had no effect on the lung pathology caused by Sw/99 variants. Interestingly, the Ty/04 KO-infected pigs showed significantly increased lung pathology at 3 days post-infection compared with pigs infected with the Ty/04 WT strain. In addition, the pulmonary levels of interleukin (IL)-6, IL-8 and gamma interferon were regulated differentially by the expression of PB1-F2. Taken together, these results indicate that PB1-F2 modulates virus replication, virulence and innate immune responses in pigs in a strain-dependent fashion.</p>
</abstract>
<funding-group><award-group><funding-source id="sp1">CDC-HHS</funding-source>
<award-id rid="sp1">1U01CI000355</award-id>
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<award-id rid="sp4">HHSN266200700010C</award-id>
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<award-group><funding-source id="sp5">USDA-ARS</funding-source>
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<custom-meta-group><custom-meta><meta-name>CopyEditor</meta-name>
<meta-value>Natalie Wilder</meta-value>
</custom-meta>
<custom-meta><meta-name>Disc-work</meta-name>
<meta-value>Sarah Ferris</meta-value>
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<meta-value>free</meta-value>
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</front>
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</record>
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