Structural Determinants for Naturally Evolving H5N1 Hemagglutinin to Switch its Receptor Specificity
Identifieur interne : 000828 ( Main/Exploration ); précédent : 000827; suivant : 000829Structural Determinants for Naturally Evolving H5N1 Hemagglutinin to Switch its Receptor Specificity
Auteurs : Kannan Tharakaraman ; Rahul Raman ; Karthik Viswanathan ; Nathan W. Stebbins ; Akila Jayaraman ; Arvind Krishnan ; V. Sasisekharan ; Ram SasisekharanSource :
- Cell [ 0092-8674 ] ; 2013.
Abstract
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.
Url:
DOI: 10.1016/j.cell.2013.05.035
PubMed: 23746829
PubMed Central: 3760228
Affiliations:
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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. 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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><affiliations><list></list><tree><noCountry><name sortKey="Jayaraman, Akila" sort="Jayaraman, Akila" uniqKey="Jayaraman A" first="Akila" last="Jayaraman">Akila Jayaraman</name><name sortKey="Krishnan, Arvind" sort="Krishnan, Arvind" uniqKey="Krishnan A" first="Arvind" last="Krishnan">Arvind Krishnan</name><name sortKey="Raman, Rahul" sort="Raman, Rahul" uniqKey="Raman R" first="Rahul" last="Raman">Rahul Raman</name><name sortKey="Sasisekharan, Ram" sort="Sasisekharan, Ram" uniqKey="Sasisekharan R" first="Ram" last="Sasisekharan">Ram Sasisekharan</name><name sortKey="Sasisekharan, V" sort="Sasisekharan, V" uniqKey="Sasisekharan V" first="V." last="Sasisekharan">V. Sasisekharan</name><name sortKey="Stebbins, Nathan W" sort="Stebbins, Nathan W" uniqKey="Stebbins N" first="Nathan W." last="Stebbins">Nathan W. Stebbins</name><name sortKey="Tharakaraman, Kannan" sort="Tharakaraman, Kannan" uniqKey="Tharakaraman K" first="Kannan" last="Tharakaraman">Kannan Tharakaraman</name><name sortKey="Viswanathan, Karthik" sort="Viswanathan, Karthik" uniqKey="Viswanathan K" first="Karthik" last="Viswanathan">Karthik Viswanathan</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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