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Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 virus

Identifieur interne : 000803 ( Pmc/Corpus ); précédent : 000802; suivant : 000804

Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 virus

Auteurs : Martin Linster ; Sander Van Boheemen ; Miranda De Graaf ; Eefje J. A. Schrauwen ; Pascal Lexmond ; Benjamin M Nz ; Theo M. Bestebroer ; Jan Baumann ; Debby Van Riel ; Guus F. Rimmelzwaan ; Albert D. M. E. Osterhaus ; Mikhail Matrosovich ; Ron A. M. Fouchier ; Sander Herfst

Source :

RBID : PMC:4003409

Abstract

SUMMARY

Recently, A/H5N1 influenza viruses were shown to acquire airborne transmissibility between ferrets upon targeted mutagenesis and virus passage. The critical genetic changes in airborne A/Indonesia/5/05 were not yet identified. Here, five substitutions proved to be sufficient to determine this airborne transmission phenotype. Substitutions in PB1 and PB2 collectively caused enhanced transcription and virus replication. One substitution increased HA thermostability and lowered the pH of membrane fusion. Two substitutions independently changed HA binding preference from α2,3 linked to α2,6 linked sialic acid receptors. The loss of a glycosylation site in HA enhanced overall binding to receptors. The acquired substitutions emerged early during ferret passage as minor variants and became dominant rapidly. Identification of substitutions that are essential for airborne transmission of avian influenza viruses between ferrets and their associated phenotypes advances our fundamental understanding of virus transmission and will increase the value of future surveillance programs and public health risk assessments.


Url:
DOI: 10.1016/j.cell.2014.02.040
PubMed: 24725402
PubMed Central: 4003409

Links to Exploration step

PMC:4003409

Le document en format XML

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<name sortKey="Osterhaus, Albert D M E" sort="Osterhaus, Albert D M E" uniqKey="Osterhaus A" first="Albert D. M. E." last="Osterhaus">Albert D. M. E. Osterhaus</name>
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<name sortKey="Matrosovich, Mikhail" sort="Matrosovich, Mikhail" uniqKey="Matrosovich M" first="Mikhail" last="Matrosovich">Mikhail Matrosovich</name>
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<name sortKey="Fouchier, Ron A M" sort="Fouchier, Ron A M" uniqKey="Fouchier R" first="Ron A. M." last="Fouchier">Ron A. M. Fouchier</name>
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<nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff>
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<title xml:lang="en" level="a" type="main">Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 virus</title>
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<name sortKey="Linster, Martin" sort="Linster, Martin" uniqKey="Linster M" first="Martin" last="Linster">Martin Linster</name>
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<name sortKey="Schrauwen, Eefje J A" sort="Schrauwen, Eefje J A" uniqKey="Schrauwen E" first="Eefje J. A." last="Schrauwen">Eefje J. A. Schrauwen</name>
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<nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff>
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<name sortKey="Lexmond, Pascal" sort="Lexmond, Pascal" uniqKey="Lexmond P" first="Pascal" last="Lexmond">Pascal Lexmond</name>
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<nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff>
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<name sortKey="M Nz, Benjamin" sort="M Nz, Benjamin" uniqKey="M Nz B" first="Benjamin" last="M Nz">Benjamin M Nz</name>
<affiliation>
<nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff>
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<name sortKey="Bestebroer, Theo M" sort="Bestebroer, Theo M" uniqKey="Bestebroer T" first="Theo M." last="Bestebroer">Theo M. Bestebroer</name>
<affiliation>
<nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff>
</affiliation>
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<author>
<name sortKey="Baumann, Jan" sort="Baumann, Jan" uniqKey="Baumann J" first="Jan" last="Baumann">Jan Baumann</name>
<affiliation>
<nlm:aff id="A2">Institute of Virology, Philipps-University, 35043 Marburg, Germany</nlm:aff>
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<name sortKey="Van Riel, Debby" sort="Van Riel, Debby" uniqKey="Van Riel D" first="Debby" last="Van Riel">Debby Van Riel</name>
<affiliation>
<nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff>
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<name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name>
<affiliation>
<nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff>
</affiliation>
</author>
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<name sortKey="Osterhaus, Albert D M E" sort="Osterhaus, Albert D M E" uniqKey="Osterhaus A" first="Albert D. M. E." last="Osterhaus">Albert D. M. E. Osterhaus</name>
<affiliation>
<nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff>
</affiliation>
</author>
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<name sortKey="Matrosovich, Mikhail" sort="Matrosovich, Mikhail" uniqKey="Matrosovich M" first="Mikhail" last="Matrosovich">Mikhail Matrosovich</name>
<affiliation>
<nlm:aff id="A2">Institute of Virology, Philipps-University, 35043 Marburg, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Fouchier, Ron A M" sort="Fouchier, Ron A M" uniqKey="Fouchier R" first="Ron A. M." last="Fouchier">Ron A. M. Fouchier</name>
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<nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff>
</affiliation>
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<name sortKey="Herfst, Sander" sort="Herfst, Sander" uniqKey="Herfst S" first="Sander" last="Herfst">Sander Herfst</name>
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<nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff>
</affiliation>
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<title level="j">Cell</title>
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<idno type="eISSN">1097-4172</idno>
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<div type="abstract" xml:lang="en">
<title>SUMMARY</title>
<p id="P3">Recently, A/H5N1 influenza viruses were shown to acquire airborne transmissibility between ferrets upon targeted mutagenesis and virus passage. The critical genetic changes in airborne A/Indonesia/5/05 were not yet identified. Here, five substitutions proved to be sufficient to determine this airborne transmission phenotype. Substitutions in PB1 and PB2 collectively caused enhanced transcription and virus replication. One substitution increased HA thermostability and lowered the pH of membrane fusion. Two substitutions independently changed HA binding preference from α2,3 linked to α2,6 linked sialic acid receptors. The loss of a glycosylation site in HA enhanced overall binding to receptors. The acquired substitutions emerged early during ferret passage as minor variants and became dominant rapidly. Identification of substitutions that are essential for airborne transmission of avian influenza viruses between ferrets and their associated phenotypes advances our fundamental understanding of virus transmission and will increase the value of future surveillance programs and public health risk assessments.</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">24725402</article-id>
<article-id pub-id-type="pmc">4003409</article-id>
<article-id pub-id-type="doi">10.1016/j.cell.2014.02.040</article-id>
<article-id pub-id-type="manuscript">NIHMS571565</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 virus</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Linster</surname>
<given-names>Martin</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref rid="FN2" ref-type="author-notes">§</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>van Boheemen</surname>
<given-names>Sander</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref rid="FN2" ref-type="author-notes">§</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>de Graaf</surname>
<given-names>Miranda</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Schrauwen</surname>
<given-names>Eefje J. A.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lexmond</surname>
<given-names>Pascal</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mänz</surname>
<given-names>Benjamin</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bestebroer</surname>
<given-names>Theo M.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Baumann</surname>
<given-names>Jan</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>van Riel</surname>
<given-names>Debby</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rimmelzwaan</surname>
<given-names>Guus F.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Osterhaus</surname>
<given-names>Albert D.M.E.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Matrosovich</surname>
<given-names>Mikhail</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fouchier</surname>
<given-names>Ron A. M.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Herfst</surname>
<given-names>Sander</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
</contrib-group>
<aff id="A1">
<label>1</label>
Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</aff>
<aff id="A2">
<label>2</label>
Institute of Virology, Philipps-University, 35043 Marburg, Germany</aff>
<author-notes>
<corresp id="FN1">
<label>*</label>
corresponding author:
<email>r.fouchier@erasmusmc.nl</email>
</corresp>
<fn id="FN2" fn-type="equal">
<label>§</label>
<p>authors contributed equally to this work</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted">
<day>16</day>
<month>4</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="ppub">
<day>10</day>
<month>4</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>10</day>
<month>4</month>
<year>2015</year>
</pub-date>
<volume>157</volume>
<issue>2</issue>
<fpage>329</fpage>
<lpage>339</lpage>
<pmc-comment>elocation-id from pubmed: 10.1016/j.cell.2014.02.040</pmc-comment>
<permissions>
<copyright-statement>© 2014 Elsevier Inc. All rights reserved.</copyright-statement>
<copyright-year>2014</copyright-year>
</permissions>
<abstract>
<title>SUMMARY</title>
<p id="P3">Recently, A/H5N1 influenza viruses were shown to acquire airborne transmissibility between ferrets upon targeted mutagenesis and virus passage. The critical genetic changes in airborne A/Indonesia/5/05 were not yet identified. Here, five substitutions proved to be sufficient to determine this airborne transmission phenotype. Substitutions in PB1 and PB2 collectively caused enhanced transcription and virus replication. One substitution increased HA thermostability and lowered the pH of membrane fusion. Two substitutions independently changed HA binding preference from α2,3 linked to α2,6 linked sialic acid receptors. The loss of a glycosylation site in HA enhanced overall binding to receptors. The acquired substitutions emerged early during ferret passage as minor variants and became dominant rapidly. Identification of substitutions that are essential for airborne transmission of avian influenza viruses between ferrets and their associated phenotypes advances our fundamental understanding of virus transmission and will increase the value of future surveillance programs and public health risk assessments.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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