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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Recent avian H5N1 viruses exhibit increased propensity for acquiring human receptor specificity</title>
<author><name sortKey="Stevens, James" sort="Stevens, James" uniqKey="Stevens J" first="James" last="Stevens">James Stevens</name>
<affiliation><nlm:aff id="A1"> Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Blixt, Ola" sort="Blixt, Ola" uniqKey="Blixt O" first="Ola" last="Blixt">Ola Blixt</name>
<affiliation><nlm:aff id="A1"> Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2"> Department of Chemical Physiology and Glycan Array Synthesis Core of the Consortium for Functional Glycomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chen, Li Mei" sort="Chen, Li Mei" uniqKey="Chen L" first="Li-Mei" last="Chen">Li-Mei Chen</name>
<affiliation><nlm:aff id="A3"> Influenza Division, Molecular Virology Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Donis, Ruben O" sort="Donis, Ruben O" uniqKey="Donis R" first="Ruben O." last="Donis">Ruben O. Donis</name>
<affiliation><nlm:aff id="A3"> Influenza Division, Molecular Virology Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Paulson, James C" sort="Paulson, James C" uniqKey="Paulson J" first="James C." last="Paulson">James C. Paulson</name>
<affiliation><nlm:aff id="A1"> Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2"> Department of Chemical Physiology and Glycan Array Synthesis Core of the Consortium for Functional Glycomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wilson, Ian A" sort="Wilson, Ian A" uniqKey="Wilson I" first="Ian A." last="Wilson">Ian A. Wilson</name>
<affiliation><nlm:aff id="A1"> Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4"> Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">18672252</idno>
<idno type="pmc">2519951</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2519951</idno>
<idno type="RBID">PMC:2519951</idno>
<idno type="doi">10.1016/j.jmb.2008.04.016</idno>
<date when="2008">2008</date>
<idno type="wicri:Area/Pmc/Corpus">000546</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000546</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Recent avian H5N1 viruses exhibit increased propensity for acquiring human receptor specificity</title>
<author><name sortKey="Stevens, James" sort="Stevens, James" uniqKey="Stevens J" first="James" last="Stevens">James Stevens</name>
<affiliation><nlm:aff id="A1"> Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Blixt, Ola" sort="Blixt, Ola" uniqKey="Blixt O" first="Ola" last="Blixt">Ola Blixt</name>
<affiliation><nlm:aff id="A1"> Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2"> Department of Chemical Physiology and Glycan Array Synthesis Core of the Consortium for Functional Glycomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chen, Li Mei" sort="Chen, Li Mei" uniqKey="Chen L" first="Li-Mei" last="Chen">Li-Mei Chen</name>
<affiliation><nlm:aff id="A3"> Influenza Division, Molecular Virology Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Donis, Ruben O" sort="Donis, Ruben O" uniqKey="Donis R" first="Ruben O." last="Donis">Ruben O. Donis</name>
<affiliation><nlm:aff id="A3"> Influenza Division, Molecular Virology Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Paulson, James C" sort="Paulson, James C" uniqKey="Paulson J" first="James C." last="Paulson">James C. Paulson</name>
<affiliation><nlm:aff id="A1"> Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2"> Department of Chemical Physiology and Glycan Array Synthesis Core of the Consortium for Functional Glycomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wilson, Ian A" sort="Wilson, Ian A" uniqKey="Wilson I" first="Ian A." last="Wilson">Ian A. Wilson</name>
<affiliation><nlm:aff id="A1"> Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4"> Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Journal of molecular biology</title>
<idno type="ISSN">0022-2836</idno>
<idno type="eISSN">1089-8638</idno>
<imprint><date when="2008">2008</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P1">Adaptation of avian influenza viruses for replication and transmission in the human host is believed to require mutations in the hemagglutinin glycoprotein (HA) which enable binding to human α2-6 sialosides and concomitant reduction in affinity for avian α2-3 linked sialosides. Here, we show by glycan microarray analyses that the two mutations responsible for such specificity changes in 1957 H2N2 and 1968 H3N2 pandemic viruses, when inserted into recombinant HAs or intact viruses of some recent avian H5N1 isolates (clade 2.2), impart such attributes. This propensity to adapt to human receptors is primarily dependent on arginine at position 193 within the receptor binding site, as well as loss of a vicinal glycosylation site. already have Widespread occurrence of these susceptible H5N1 clade 2.2 influenza strains has already occurred in Europe, the Middle East, and Africa. Thus, these avian strains should be considered ‘high-risk’, because of their significantly lower threshold for acquiring human receptor specificity and, therefore, warrant increased surveillance and further study.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">2985088R</journal-id>
<journal-id journal-id-type="pubmed-jr-id">4967</journal-id>
<journal-id journal-id-type="nlm-ta">J Mol Biol</journal-id>
<journal-title>Journal of molecular biology</journal-title>
<issn pub-type="ppub">0022-2836</issn>
<issn pub-type="epub">1089-8638</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">18672252</article-id>
<article-id pub-id-type="pmc">2519951</article-id>
<article-id pub-id-type="doi">10.1016/j.jmb.2008.04.016</article-id>
<article-id pub-id-type="manuscript">NIHMS47345</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Recent avian H5N1 viruses exhibit increased propensity for acquiring human receptor specificity</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Stevens</surname>
<given-names>James</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
<xref rid="FN2" ref-type="author-notes">#</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Blixt</surname>
<given-names>Ola</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A2" ref-type="aff">2</xref>
<xref rid="FN3" ref-type="author-notes">†</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chen</surname>
<given-names>Li-Mei</given-names>
</name>
<xref rid="A3" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Donis</surname>
<given-names>Ruben O.</given-names>
</name>
<xref rid="A3" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Paulson</surname>
<given-names>James C.</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wilson</surname>
<given-names>Ian A.</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A4" ref-type="aff">4</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</aff>
<aff id="A2"><label>2</label>
Department of Chemical Physiology and Glycan Array Synthesis Core of the Consortium for Functional Glycomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</aff>
<aff id="A3"><label>3</label>
Influenza Division, Molecular Virology Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333</aff>
<aff id="A4"><label>4</label>
Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</aff>
<author-notes><corresp id="FN1">* To whom correspondence should be addressed: E-mail: <email>wilson@scripps.edu</email>
, <email>james.stevens@cdc.hhs.gov</email>
</corresp>
<fn id="FN2" fn-type="present-address"><label>#</label>
<p>Current address: Influenza Division, Molecular Virology Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333</p>
</fn>
<fn id="FN3" fn-type="present-address"><label>†</label>
<p>Current address: Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>21</day>
<month>4</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="epub"><day>11</day>
<month>4</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="ppub"><day>19</day>
<month>9</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>19</day>
<month>3</month>
<year>2009</year>
</pub-date>
<volume>381</volume>
<issue>5</issue>
<fpage>1382</fpage>
<lpage>1394</lpage>
<abstract><p id="P1">Adaptation of avian influenza viruses for replication and transmission in the human host is believed to require mutations in the hemagglutinin glycoprotein (HA) which enable binding to human α2-6 sialosides and concomitant reduction in affinity for avian α2-3 linked sialosides. Here, we show by glycan microarray analyses that the two mutations responsible for such specificity changes in 1957 H2N2 and 1968 H3N2 pandemic viruses, when inserted into recombinant HAs or intact viruses of some recent avian H5N1 isolates (clade 2.2), impart such attributes. This propensity to adapt to human receptors is primarily dependent on arginine at position 193 within the receptor binding site, as well as loss of a vicinal glycosylation site. already have Widespread occurrence of these susceptible H5N1 clade 2.2 influenza strains has already occurred in Europe, the Middle East, and Africa. Thus, these avian strains should be considered ‘high-risk’, because of their significantly lower threshold for acquiring human receptor specificity and, therefore, warrant increased surveillance and further study.</p>
</abstract>
<kwd-group><kwd>Influenza</kwd>
<kwd>glycan array</kwd>
<kwd>hemagglutinin</kwd>
<kwd>receptor specificity</kwd>
<kwd>H5N1</kwd>
</kwd-group>
<contract-num rid="GM1">U54 GM062116-070012</contract-num>
<contract-num rid="GM1">U54 GM062116-07</contract-num>
<contract-num rid="AI1">R37 AI042266-11</contract-num>
<contract-num rid="GM1">R01 GM060938-09</contract-num>
<contract-num rid="CA1">R01 CA058896-15</contract-num>
<contract-num rid="AI1">P01 AI058113-040002</contract-num>
<contract-sponsor id="GM1">National Institute of General Medical Sciences : NIGMS</contract-sponsor>
<contract-sponsor id="AI1">National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID</contract-sponsor>
<contract-sponsor id="CA1">National Cancer Institute : NCI</contract-sponsor>
</article-meta>
</front>
</pmc>
</record>
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