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

Identifieur interne : 000C70 ( Main/Exploration ); précédent : 000C69; suivant : 000C71

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

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

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


Affiliations:


Links toward previous steps (curation, corpus...)


Le document en format XML

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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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<name sortKey="Raman, Rahul" sort="Raman, Rahul" uniqKey="Raman R" first="Rahul" last="Raman">Rahul Raman</name>
<affiliation wicri:level="2">
<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>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>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</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Sasisekharan, Ram" sort="Sasisekharan, Ram" uniqKey="Sasisekharan R" first="Ram" last="Sasisekharan">Ram Sasisekharan</name>
<affiliation wicri:level="2">
<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>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>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</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Katz, Jacqueline M" sort="Katz, Jacqueline M" uniqKey="Katz J" first="Jacqueline M." last="Katz">Jacqueline M. Katz</name>
<affiliation wicri:level="2">
<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>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control & Prevention, 1600 Clifton Road, MS-G16, Atlanta, GA 30333</wicri:regionArea>
<placeName>
<region type="state">Géorgie (États-Unis)</region>
</placeName>
</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 wicri:level="2">
<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>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control & Prevention, 1600 Clifton Road, MS-G16, Atlanta, GA 30333</wicri:regionArea>
<placeName>
<region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Virology</title>
<idno type="ISSN">0042-6822</idno>
<idno type="eISSN">1096-0341</idno>
<imprint>
<date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<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>
</TEI>
<affiliations>
<list>
<country>
<li>Danemark</li>
<li>États-Unis</li>
</country>
<region>
<li>Californie</li>
<li>Géorgie (États-Unis)</li>
<li>Massachusetts</li>
</region>
</list>
<tree>
<country name="États-Unis">
<region name="Géorgie (États-Unis)">
<name sortKey="Maines, Taronna R" sort="Maines, Taronna R" uniqKey="Maines T" first="Taronna R." last="Maines">Taronna R. Maines</name>
</region>
<name sortKey="Belser, Jessica A" sort="Belser, Jessica A" uniqKey="Belser J" first="Jessica A." last="Belser">Jessica A. Belser</name>
<name sortKey="Chen, Li Mei" sort="Chen, Li Mei" uniqKey="Chen L" first="Li-Mei" last="Chen">Li-Mei Chen</name>
<name sortKey="Cox, Nancy J" sort="Cox, Nancy J" uniqKey="Cox N" first="Nancy J." last="Cox">Nancy J. Cox</name>
<name sortKey="Donis, Ruben O" sort="Donis, Ruben O" uniqKey="Donis R" first="Ruben O." last="Donis">Ruben O. Donis</name>
<name sortKey="Gustin, Kortney M" sort="Gustin, Kortney M" uniqKey="Gustin K" first="Kortney M." last="Gustin">Kortney M. Gustin</name>
<name sortKey="Katz, Jacqueline M" sort="Katz, Jacqueline M" uniqKey="Katz J" first="Jacqueline M." last="Katz">Jacqueline M. Katz</name>
<name sortKey="Pappas, Claudia" sort="Pappas, Claudia" uniqKey="Pappas C" first="Claudia" last="Pappas">Claudia Pappas</name>
<name sortKey="Paulson, James C" sort="Paulson, James C" uniqKey="Paulson J" first="James C." last="Paulson">James C. Paulson</name>
<name sortKey="Pearce, Melissa B" sort="Pearce, Melissa B" uniqKey="Pearce M" first="Melissa B." last="Pearce">Melissa B. Pearce</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="Stevens, James" sort="Stevens, James" uniqKey="Stevens J" first="James" last="Stevens">James Stevens</name>
<name sortKey="Tumpey, Terrence M" sort="Tumpey, Terrence M" uniqKey="Tumpey T" first="Terrence M." last="Tumpey">Terrence M. Tumpey</name>
<name sortKey="Van Hoeven, Neal" sort="Van Hoeven, Neal" uniqKey="Van Hoeven N" first="Neal" last="Van Hoeven">Neal Van Hoeven</name>
</country>
<country name="Danemark">
<noRegion>
<name sortKey="Blixt, Ola" sort="Blixt, Ola" uniqKey="Blixt O" first="Ola" last="Blixt">Ola Blixt</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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