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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Influenza H1N1 A/Solomon Island/3/06 Virus Receptor Binding Specificity Correlates with Virus Pathogenicity, Antigenicity, and Immunogenicity in Ferrets <xref ref-type="fn" rid="fn2">▿</xref>
</title>
<author><name sortKey="Xu, Qi" sort="Xu, Qi" uniqKey="Xu Q" first="Qi" last="Xu">Qi Xu</name>
<affiliation><nlm:aff id="aff0">MedImmune, 319 North Bernardo Avenue, Mountain View, California 94043</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wang, Weijia" sort="Wang, Weijia" uniqKey="Wang W" first="Weijia" last="Wang">Weijia Wang</name>
<affiliation><nlm:aff id="aff0">MedImmune, 319 North Bernardo Avenue, Mountain View, California 94043</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cheng, Xing" sort="Cheng, Xing" uniqKey="Cheng X" first="Xing" last="Cheng">Xing Cheng</name>
<affiliation><nlm:aff id="aff0">MedImmune, 319 North Bernardo Avenue, Mountain View, California 94043</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zengel, James" sort="Zengel, James" uniqKey="Zengel J" first="James" last="Zengel">James Zengel</name>
<affiliation><nlm:aff id="aff0">MedImmune, 319 North Bernardo Avenue, Mountain View, California 94043</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jin, Hong" sort="Jin, Hong" uniqKey="Jin H" first="Hong" last="Jin">Hong Jin</name>
<affiliation><nlm:aff id="aff0">MedImmune, 319 North Bernardo Avenue, Mountain View, California 94043</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">20200248</idno>
<idno type="pmc">2863823</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2863823</idno>
<idno type="RBID">PMC:2863823</idno>
<idno type="doi">10.1128/JVI.02489-09</idno>
<date when="2010">2010</date>
<idno type="wicri:Area/Pmc/Corpus">000716</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000716</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Influenza H1N1 A/Solomon Island/3/06 Virus Receptor Binding Specificity Correlates with Virus Pathogenicity, Antigenicity, and Immunogenicity in Ferrets <xref ref-type="fn" rid="fn2">▿</xref>
</title>
<author><name sortKey="Xu, Qi" sort="Xu, Qi" uniqKey="Xu Q" first="Qi" last="Xu">Qi Xu</name>
<affiliation><nlm:aff id="aff0">MedImmune, 319 North Bernardo Avenue, Mountain View, California 94043</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wang, Weijia" sort="Wang, Weijia" uniqKey="Wang W" first="Weijia" last="Wang">Weijia Wang</name>
<affiliation><nlm:aff id="aff0">MedImmune, 319 North Bernardo Avenue, Mountain View, California 94043</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cheng, Xing" sort="Cheng, Xing" uniqKey="Cheng X" first="Xing" last="Cheng">Xing Cheng</name>
<affiliation><nlm:aff id="aff0">MedImmune, 319 North Bernardo Avenue, Mountain View, California 94043</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zengel, James" sort="Zengel, James" uniqKey="Zengel J" first="James" last="Zengel">James Zengel</name>
<affiliation><nlm:aff id="aff0">MedImmune, 319 North Bernardo Avenue, Mountain View, California 94043</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jin, Hong" sort="Jin, Hong" uniqKey="Jin H" first="Hong" last="Jin">Hong Jin</name>
<affiliation><nlm:aff id="aff0">MedImmune, 319 North Bernardo Avenue, Mountain View, California 94043</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>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Influenza viruses attach to cells via a sialic acid moiety (sialic acid receptor) that is α2-3 linked or α2-6 linked to galactose (α2-3SAL or α2-6SAL); sialic acid acts as a receptor for the virus. Using lectin staining, we demonstrated that the α2-6SAL configuration is predominant in the respiratory tract of ferrets, including trachea, bronchus, and lung alveolus tissues. Recombinant wild-type (rWT) influenza A/Solomon Island/3/06 (SI06) (H1N1) viruses were constructed to assess the impact of the hemagglutinin (HA) variations (amino acids 190 or 226) identified in natural variants on virus replication in the upper and lower respiratory tract of ferrets, as well as virus antigenicity and immunogenicity. A single amino acid change at residue 226 (from Gln to Arg) in the HA of SI06 resulted in the complete loss of binding to α2-6SAL and a concomitant loss of the virus's ability to replicate in the lower respiratory tract of ferrets. In contrast, the virus with Gln226 in the HA protein has a receptor binding preference for α2-6SAL and replicates efficiently in the lungs. There was a good correlation between viral replication in the lungs of ferrets and disease symptoms. In addition, we also showed that the 190 and 226 residues affected viral antigenicity and immunogenicity. Our data emphasize the necessity of thoroughly assessing wild-type influenza viruses for their suitability as reference strains and for carefully selecting the HA antigen for vaccine production during annual influenza vaccine evaluation processes.</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">20200248</article-id>
<article-id pub-id-type="pmc">2863823</article-id>
<article-id pub-id-type="publisher-id">2489-09</article-id>
<article-id pub-id-type="doi">10.1128/JVI.02489-09</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Pathogenesis and Immunity</subject>
</subj-group>
</article-categories>
<title-group><article-title>Influenza H1N1 A/Solomon Island/3/06 Virus Receptor Binding Specificity Correlates with Virus Pathogenicity, Antigenicity, and Immunogenicity in Ferrets <xref ref-type="fn" rid="fn2">▿</xref>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Xu</surname>
<given-names>Qi</given-names>
</name>
<xref ref-type="aff" rid="aff0"></xref>
<xref ref-type="fn" rid="fn1">#</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Weijia</given-names>
</name>
<xref ref-type="aff" rid="aff0"></xref>
<xref ref-type="fn" rid="fn1">#</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cheng</surname>
<given-names>Xing</given-names>
</name>
<xref ref-type="aff" rid="aff0"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zengel</surname>
<given-names>James</given-names>
</name>
<xref ref-type="aff" rid="aff0"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jin</surname>
<given-names>Hong</given-names>
</name>
<xref ref-type="aff" rid="aff0"></xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
</contrib-group>
<aff id="aff0">MedImmune, 319 North Bernardo Avenue, Mountain View, California 94043</aff>
<author-notes><corresp id="cor1"><label>*</label>
Corresponding author. Mailing address: MedImmune, 319 North Bernardo Ave., Mountain View, CA 94043. Phone: (650) 603-2367. Fax: (650) 603-3367. E-mail: <email>jinh@medimmune.com</email>
</corresp>
<fn id="fn1"><label>#</label>
<p>Both authors contributed equally to the work.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>5</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="epub"><day>3</day>
<month>3</month>
<year>2010</year>
</pub-date>
<volume>84</volume>
<issue>10</issue>
<fpage>4936</fpage>
<lpage>4945</lpage>
<history><date date-type="received"><day>25</day>
<month>11</month>
<year>2009</year>
</date>
<date date-type="accepted"><day>19</day>
<month>2</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="zjv01010004936.pdf"></self-uri>
<abstract><p>Influenza viruses attach to cells via a sialic acid moiety (sialic acid receptor) that is α2-3 linked or α2-6 linked to galactose (α2-3SAL or α2-6SAL); sialic acid acts as a receptor for the virus. Using lectin staining, we demonstrated that the α2-6SAL configuration is predominant in the respiratory tract of ferrets, including trachea, bronchus, and lung alveolus tissues. Recombinant wild-type (rWT) influenza A/Solomon Island/3/06 (SI06) (H1N1) viruses were constructed to assess the impact of the hemagglutinin (HA) variations (amino acids 190 or 226) identified in natural variants on virus replication in the upper and lower respiratory tract of ferrets, as well as virus antigenicity and immunogenicity. A single amino acid change at residue 226 (from Gln to Arg) in the HA of SI06 resulted in the complete loss of binding to α2-6SAL and a concomitant loss of the virus's ability to replicate in the lower respiratory tract of ferrets. In contrast, the virus with Gln226 in the HA protein has a receptor binding preference for α2-6SAL and replicates efficiently in the lungs. There was a good correlation between viral replication in the lungs of ferrets and disease symptoms. In addition, we also showed that the 190 and 226 residues affected viral antigenicity and immunogenicity. Our data emphasize the necessity of thoroughly assessing wild-type influenza viruses for their suitability as reference strains and for carefully selecting the HA antigen for vaccine production during annual influenza vaccine evaluation processes.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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