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Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses☆

Identifieur interne : 000782 ( Pmc/Corpus ); précédent : 000781; suivant : 000783

Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses☆

Auteurs : Taronna R. Maines ; Li-Mei Chen ; Neal Van Hoeven ; Terrence M. Tumpey ; Ola Blixt ; Jessica A. Belser ; Kortney M. Gustin ; Melissa B. Pearce ; Claudia Pappas ; James Stevens ; Nancy J. Cox ; James C. Paulson ; Rahul Raman ; Ram Sasisekharan ; Jacqueline M. Katz ; Ruben O. Donis

Source :

RBID : PMC:5470842

Abstract

Although H5N1 influenza viruses have been responsible for hundreds of human infections, these avian influenza viruses have not fully adapted to the human host. The lack of sustained transmission in humans may be due, in part, to their avian-like receptor preference. Here, we have introduced receptor binding domain mutations within the hemagglutinin (HA) gene of two H5N1 viruses and evaluated changes in receptor binding specificity by glycan microarray analysis. The impact of these mutations on replication efficiency was assessed in vitro and in vivo. Although certain mutations switched the receptor binding preference of the H5 HA, the rescued mutant viruses displayed reduced replication in vitro and delayed peak virus shedding in ferrets. An improvement in transmission efficiency was not observed with any of the mutants compared to the parental viruses, indicating that alternative molecular changes are required for H5N1 viruses to fully adapt to humans and to acquire pandemic capability.


Url:
DOI: 10.1016/j.virol.2011.02.015
PubMed: 21397290
PubMed Central: 5470842

Links to Exploration step

PMC:5470842

Le document en format XML

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<name sortKey="Gustin, Kortney M" sort="Gustin, Kortney M" uniqKey="Gustin K" first="Kortney M." last="Gustin">Kortney M. Gustin</name>
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<nlm:aff id="A1">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control & Prevention, 1600 Clifton Road, MS-G16, Atlanta, GA 30333, USA</nlm:aff>
</affiliation>
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<name sortKey="Pearce, Melissa B" sort="Pearce, Melissa B" uniqKey="Pearce M" first="Melissa B." last="Pearce">Melissa B. Pearce</name>
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<nlm:aff id="A1">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control & Prevention, 1600 Clifton Road, MS-G16, Atlanta, GA 30333, USA</nlm:aff>
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<name sortKey="Pappas, Claudia" sort="Pappas, Claudia" uniqKey="Pappas C" first="Claudia" last="Pappas">Claudia Pappas</name>
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<name sortKey="Stevens, James" sort="Stevens, James" uniqKey="Stevens J" first="James" last="Stevens">James Stevens</name>
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<nlm:aff id="A1">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control & Prevention, 1600 Clifton Road, MS-G16, Atlanta, GA 30333, USA</nlm:aff>
</affiliation>
</author>
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<name sortKey="Cox, Nancy J" sort="Cox, Nancy J" uniqKey="Cox N" first="Nancy J." last="Cox">Nancy J. Cox</name>
<affiliation>
<nlm:aff id="A1">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control & Prevention, 1600 Clifton Road, MS-G16, Atlanta, GA 30333, USA</nlm:aff>
</affiliation>
</author>
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<name sortKey="Paulson, James C" sort="Paulson, James C" uniqKey="Paulson J" first="James C." last="Paulson">James C. Paulson</name>
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<nlm:aff id="A3">Department of Physiological Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
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<author>
<name sortKey="Raman, Rahul" sort="Raman, Rahul" uniqKey="Raman R" first="Rahul" last="Raman">Rahul Raman</name>
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<name sortKey="Sasisekharan, Ram" sort="Sasisekharan, Ram" uniqKey="Sasisekharan R" first="Ram" last="Sasisekharan">Ram Sasisekharan</name>
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<nlm:aff id="A4">Harvard-MIT Division of Health Sciences and Technology, Koch Institute of Integrative Cancer Research, Department of Biological Engineering, Massachusetts Institute of Technology, 15–561, 77 Massachusetts Avenue, Cambridge, MA 02139, USA</nlm:aff>
</affiliation>
</author>
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<name sortKey="Katz, Jacqueline M" sort="Katz, Jacqueline M" uniqKey="Katz J" first="Jacqueline M." last="Katz">Jacqueline M. Katz</name>
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<nlm:aff id="A1">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control & Prevention, 1600 Clifton Road, MS-G16, Atlanta, GA 30333, USA</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="A1">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control & Prevention, 1600 Clifton Road, MS-G16, Atlanta, GA 30333, USA</nlm:aff>
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<p id="P1">Although H5N1 influenza viruses have been responsible for hundreds of human infections, these avian influenza viruses have not fully adapted to the human host. The lack of sustained transmission in humans may be due, in part, to their avian-like receptor preference. Here, we have introduced receptor binding domain mutations within the hemagglutinin (HA) gene of two H5N1 viruses and evaluated changes in receptor binding specificity by glycan microarray analysis. The impact of these mutations on replication efficiency was assessed
<italic>in vitro</italic>
and
<italic>in vivo</italic>
. Although certain mutations switched the receptor binding preference of the H5 HA, the rescued mutant viruses displayed reduced replication
<italic>in vitro</italic>
and delayed peak virus shedding in ferrets. An improvement in transmission efficiency was not observed with any of the mutants compared to the parental viruses, indicating that alternative molecular changes are required for H5N1 viruses to fully adapt to humans and to acquire pandemic capability.</p>
</div>
</front>
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<contrib contrib-type="author">
<name>
<surname>Maines</surname>
<given-names>Taronna R.</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref rid="FN2" ref-type="author-notes">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chen</surname>
<given-names>Li-Mei</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref rid="FN2" ref-type="author-notes">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Van Hoeven</surname>
<given-names>Neal</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tumpey</surname>
<given-names>Terrence M.</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Blixt</surname>
<given-names>Ola</given-names>
</name>
<xref ref-type="aff" rid="A2">b</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Belser</surname>
<given-names>Jessica A.</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gustin</surname>
<given-names>Kortney M.</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pearce</surname>
<given-names>Melissa B.</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pappas</surname>
<given-names>Claudia</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Stevens</surname>
<given-names>James</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cox</surname>
<given-names>Nancy J.</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Paulson</surname>
<given-names>James C.</given-names>
</name>
<xref ref-type="aff" rid="A3">c</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Raman</surname>
<given-names>Rahul</given-names>
</name>
<xref ref-type="aff" rid="A4">d</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sasisekharan</surname>
<given-names>Ram</given-names>
</name>
<xref ref-type="aff" rid="A4">d</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Katz</surname>
<given-names>Jacqueline M.</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Donis</surname>
<given-names>Ruben O.</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
</contrib-group>
<aff id="A1">
<label>a</label>
Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control & Prevention, 1600 Clifton Road, MS-G16, Atlanta, GA 30333, USA</aff>
<aff id="A2">
<label>b</label>
Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark</aff>
<aff id="A3">
<label>c</label>
Department of Physiological Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</aff>
<aff id="A4">
<label>d</label>
Harvard-MIT Division of Health Sciences and Technology, Koch Institute of Integrative Cancer Research, Department of Biological Engineering, Massachusetts Institute of Technology, 15–561, 77 Massachusetts Avenue, Cambridge, MA 02139, USA</aff>
<author-notes>
<corresp id="FN1">
<label>*</label>
Corresponding authors:
<email>rams@mit.edu</email>
(R. Sasisekharan),
<email>jkatz@cdc.gov</email>
(J.M. Katz),
<email>rdonis@cdc.gov</email>
(R.O. Donis)</corresp>
<fn id="FN2" fn-type="equal">
<label>1</label>
<p>Denotes equal contribution.</p>
</fn>
<fn fn-type="COI-statement" id="FN3">
<label></label>
<p>The authors wish to report no competing interests associated with this manuscript.</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted">
<day>13</day>
<month>4</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="epub">
<day>23</day>
<month>3</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="ppub">
<day>25</day>
<month>4</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>14</day>
<month>6</month>
<year>2017</year>
</pub-date>
<volume>413</volume>
<issue>1</issue>
<fpage>139</fpage>
<lpage>147</lpage>
<pmc-comment>elocation-id from pubmed: 10.1016/j.virol.2011.02.015</pmc-comment>
<abstract>
<p id="P1">Although H5N1 influenza viruses have been responsible for hundreds of human infections, these avian influenza viruses have not fully adapted to the human host. The lack of sustained transmission in humans may be due, in part, to their avian-like receptor preference. Here, we have introduced receptor binding domain mutations within the hemagglutinin (HA) gene of two H5N1 viruses and evaluated changes in receptor binding specificity by glycan microarray analysis. The impact of these mutations on replication efficiency was assessed
<italic>in vitro</italic>
and
<italic>in vivo</italic>
. Although certain mutations switched the receptor binding preference of the H5 HA, the rescued mutant viruses displayed reduced replication
<italic>in vitro</italic>
and delayed peak virus shedding in ferrets. An improvement in transmission efficiency was not observed with any of the mutants compared to the parental viruses, indicating that alternative molecular changes are required for H5N1 viruses to fully adapt to humans and to acquire pandemic capability.</p>
</abstract>
<kwd-group>
<kwd>Influenza virus</kwd>
<kwd>Transmission</kwd>
<kwd>Ferrets</kwd>
<kwd>H5N1 virus</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>

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