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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Structural Determinants for Naturally Evolving H5N1 Hemagglutinin to Switch its Receptor Specificity</title>
<author><name sortKey="Tharakaraman, Kannan" sort="Tharakaraman, Kannan" uniqKey="Tharakaraman K" first="Kannan" last="Tharakaraman">Kannan Tharakaraman</name>
</author>
<author><name sortKey="Raman, Rahul" sort="Raman, Rahul" uniqKey="Raman R" first="Rahul" last="Raman">Rahul Raman</name>
</author>
<author><name sortKey="Viswanathan, Karthik" sort="Viswanathan, Karthik" uniqKey="Viswanathan K" first="Karthik" last="Viswanathan">Karthik Viswanathan</name>
</author>
<author><name sortKey="Stebbins, Nathan W" sort="Stebbins, Nathan W" uniqKey="Stebbins N" first="Nathan W." last="Stebbins">Nathan W. Stebbins</name>
</author>
<author><name sortKey="Jayaraman, Akila" sort="Jayaraman, Akila" uniqKey="Jayaraman A" first="Akila" last="Jayaraman">Akila Jayaraman</name>
</author>
<author><name sortKey="Krishnan, Arvind" sort="Krishnan, Arvind" uniqKey="Krishnan A" first="Arvind" last="Krishnan">Arvind Krishnan</name>
</author>
<author><name sortKey="Sasisekharan, V" sort="Sasisekharan, V" uniqKey="Sasisekharan V" first="V." last="Sasisekharan">V. Sasisekharan</name>
</author>
<author><name sortKey="Sasisekharan, Ram" sort="Sasisekharan, Ram" uniqKey="Sasisekharan R" first="Ram" last="Sasisekharan">Ram Sasisekharan</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">23746829</idno>
<idno type="pmc">3760228</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760228</idno>
<idno type="RBID">PMC:3760228</idno>
<idno type="doi">10.1016/j.cell.2013.05.035</idno>
<date when="2013">2013</date>
<idno type="wicri:Area/Pmc/Corpus">000802</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000802</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Structural Determinants for Naturally Evolving H5N1 Hemagglutinin to Switch its Receptor Specificity</title>
<author><name sortKey="Tharakaraman, Kannan" sort="Tharakaraman, Kannan" uniqKey="Tharakaraman K" first="Kannan" last="Tharakaraman">Kannan Tharakaraman</name>
</author>
<author><name sortKey="Raman, Rahul" sort="Raman, Rahul" uniqKey="Raman R" first="Rahul" last="Raman">Rahul Raman</name>
</author>
<author><name sortKey="Viswanathan, Karthik" sort="Viswanathan, Karthik" uniqKey="Viswanathan K" first="Karthik" last="Viswanathan">Karthik Viswanathan</name>
</author>
<author><name sortKey="Stebbins, Nathan W" sort="Stebbins, Nathan W" uniqKey="Stebbins N" first="Nathan W." last="Stebbins">Nathan W. Stebbins</name>
</author>
<author><name sortKey="Jayaraman, Akila" sort="Jayaraman, Akila" uniqKey="Jayaraman A" first="Akila" last="Jayaraman">Akila Jayaraman</name>
</author>
<author><name sortKey="Krishnan, Arvind" sort="Krishnan, Arvind" uniqKey="Krishnan A" first="Arvind" last="Krishnan">Arvind Krishnan</name>
</author>
<author><name sortKey="Sasisekharan, V" sort="Sasisekharan, V" uniqKey="Sasisekharan V" first="V." last="Sasisekharan">V. Sasisekharan</name>
</author>
<author><name sortKey="Sasisekharan, Ram" sort="Sasisekharan, Ram" uniqKey="Sasisekharan R" first="Ram" last="Sasisekharan">Ram Sasisekharan</name>
</author>
</analytic>
<series><title level="j">Cell</title>
<idno type="ISSN">0092-8674</idno>
<idno type="eISSN">1097-4172</idno>
<imprint><date when="2013">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>SUMMARY</title>
<p id="P1">Of the factors governing human-to-human transmission of the highly pathogenic avian-adapted H5N1 virus, the most critical is the acquisition of mutations on the viral hemagglutinin (HA) to “quantitatively switch” its binding from avian to human glycan receptors. Herein, we describe a structural framework that outlines a necessary set of H5 HA receptor binding site (RBS) features required for the H5 HA to quantitatively switch its preference to human receptors. We show here that the same RBS HA mutations that lead to aerosol transmission of A/Vietnam/1203/04 and A/Indonesia/5/05 viruses, when introduced in currently circulating H5N1, do not lead to quantitative switch in receptor preference. We demonstrate that HAs from circulating clades require as few as a single base-pair mutation to quantitatively switch their binding to human receptors. The mutations identified by this study can be used to monitor the emergence of strains having human-to-human transmission potential.</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>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0413066</journal-id>
<journal-id journal-id-type="pubmed-jr-id">2830</journal-id>
<journal-id journal-id-type="nlm-ta">Cell</journal-id>
<journal-id journal-id-type="iso-abbrev">Cell</journal-id>
<journal-title-group><journal-title>Cell</journal-title>
</journal-title-group>
<issn pub-type="ppub">0092-8674</issn>
<issn pub-type="epub">1097-4172</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">23746829</article-id>
<article-id pub-id-type="pmc">3760228</article-id>
<article-id pub-id-type="doi">10.1016/j.cell.2013.05.035</article-id>
<article-id pub-id-type="manuscript">NIHMS485501</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Structural Determinants for Naturally Evolving H5N1 Hemagglutinin to Switch its Receptor Specificity</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Tharakaraman</surname>
<given-names>Kannan</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Raman</surname>
<given-names>Rahul</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Viswanathan</surname>
<given-names>Karthik</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Stebbins</surname>
<given-names>Nathan W.</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Jayaraman</surname>
<given-names>Akila</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Krishnan</surname>
<given-names>Arvind</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Sasisekharan</surname>
<given-names>V.</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Sasisekharan</surname>
<given-names>Ram</given-names>
</name>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<aff id="A1">Department of Biological Engineering, Koch Institute of Integrative Cancer Research, Infectious Diseases Inter-disciplinary Research Group, Singapore-MIT Alliance for Research & Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge MA 02139</aff>
</contrib-group>
<author-notes><corresp id="cor1"><label>*</label>
To whom correspondence should be addressed: <email>rams@mit.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>8</day>
<month>8</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epub"><day>06</day>
<month>6</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="ppub"><day>20</day>
<month>6</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>20</day>
<month>6</month>
<year>2014</year>
</pub-date>
<volume>153</volume>
<issue>7</issue>
<fpage>1475</fpage>
<lpage>1485</lpage>
<permissions><copyright-statement>© 2013 Elsevier Inc. All rights reserved.</copyright-statement>
<copyright-year>2013</copyright-year>
</permissions>
<abstract><title>SUMMARY</title>
<p id="P1">Of the factors governing human-to-human transmission of the highly pathogenic avian-adapted H5N1 virus, the most critical is the acquisition of mutations on the viral hemagglutinin (HA) to “quantitatively switch” its binding from avian to human glycan receptors. Herein, we describe a structural framework that outlines a necessary set of H5 HA receptor binding site (RBS) features required for the H5 HA to quantitatively switch its preference to human receptors. We show here that the same RBS HA mutations that lead to aerosol transmission of A/Vietnam/1203/04 and A/Indonesia/5/05 viruses, when introduced in currently circulating H5N1, do not lead to quantitative switch in receptor preference. We demonstrate that HAs from circulating clades require as few as a single base-pair mutation to quantitatively switch their binding to human receptors. The mutations identified by this study can be used to monitor the emergence of strains having human-to-human transmission potential.</p>
</abstract>
<funding-group><award-group><funding-source country="United States">National Institute of Environmental Health Sciences : NIEHS</funding-source>
<award-id>T32 ES007020 || ES</award-id>
</award-group>
<award-group><funding-source country="United States">National Institute of General Medical Sciences : NIGMS</funding-source>
<award-id>R01 GM057073 || GM</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
</record>
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