Natural and directed antigenic drift of the H1 influenza virus hemagglutinin stalk domain
Identifieur interne : 000289 ( Main/Exploration ); précédent : 000288; suivant : 000290Natural and directed antigenic drift of the H1 influenza virus hemagglutinin stalk domain
Auteurs : Christopher S. Anderson ; Sandra Ortega ; Francisco A. Chaves ; Amelia M. Clark ; Hongmei Yang [États-Unis] ; David J. Topham ; Marta L. DediegoSource :
- Scientific Reports [ 2045-2322 ] ; 2017.
Abstract
The induction of antibodies specific for the influenza HA protein stalk domain is being pursued as a universal strategy against influenza virus infections. However, little work has been done looking at natural or induced antigenic variability in this domain and the effects on viral fitness. We analyzed human H1 HA head and stalk domain sequences and found substantial variability in both, although variability was highest in the head region. Furthermore, using human immune sera from pandemic A/California/04/2009 immune subjects and mAbs specific for the stalk domain, viruses were selected
Url:
DOI: 10.1038/s41598-017-14931-7
PubMed: 29097696
PubMed Central: 5668287
Affiliations:
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Natural and directed antigenic drift of the H1 influenza virus hemagglutinin stalk domain</title>
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<front><div type="abstract" xml:lang="en"><p id="Par1">The induction of antibodies specific for the influenza HA protein stalk domain is being pursued as a universal strategy against influenza virus infections. However, little work has been done looking at natural or induced antigenic variability in this domain and the effects on viral fitness. We analyzed human H1 HA head and stalk domain sequences and found substantial variability in both, although variability was highest in the head region. Furthermore, using human immune sera from pandemic A/California/04/2009 immune subjects and mAbs specific for the stalk domain, viruses were selected <italic>in vitro</italic>
containing mutations in both domains that partially contributed to immune evasion. Recombinant viruses encoding amino acid changes in the HA stalk domain replicated well <italic>in vitro</italic>
, and viruses incorporating two of the stalk mutations retained pathogenicity <italic>in vivo</italic>
. These findings demonstrate that the HA protein stalk domain can undergo limited drift under immune pressure and the viruses can retain fitness and virulence <italic>in vivo</italic>
, findings which are important to consider in the context of vaccination targeting this domain.</p>
</div>
</front>
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<author><name sortKey="Alvarado Facundo, E" uniqKey="Alvarado Facundo E">E Alvarado-Facundo</name>
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<author><name sortKey="Ribas Aparicio, Rm" uniqKey="Ribas Aparicio R">RM Ribas-Aparicio</name>
</author>
<author><name sortKey="Castelan Vega, Ja" uniqKey="Castelan Vega J">JA Castelan-Vega</name>
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</biblStruct>
<biblStruct><analytic><author><name sortKey="Lin, S" uniqKey="Lin S">S Lin</name>
</author>
<author><name sortKey="Naim, Hy" uniqKey="Naim H">HY Naim</name>
</author>
<author><name sortKey="Rodriguez, Ac" uniqKey="Rodriguez A">AC Rodriguez</name>
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<author><name sortKey="Roth, Mg" uniqKey="Roth M">MG Roth</name>
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<biblStruct><analytic><author><name sortKey="Chai, N" uniqKey="Chai N">N Chai</name>
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<biblStruct><analytic><author><name sortKey="Whittle, Jrr" uniqKey="Whittle J">JRR Whittle</name>
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<tree><noCountry><name sortKey="Anderson, Christopher S" sort="Anderson, Christopher S" uniqKey="Anderson C" first="Christopher S." last="Anderson">Christopher S. Anderson</name>
<name sortKey="Chaves, Francisco A" sort="Chaves, Francisco A" uniqKey="Chaves F" first="Francisco A." last="Chaves">Francisco A. Chaves</name>
<name sortKey="Clark, Amelia M" sort="Clark, Amelia M" uniqKey="Clark A" first="Amelia M." last="Clark">Amelia M. Clark</name>
<name sortKey="Dediego, Marta L" sort="Dediego, Marta L" uniqKey="Dediego M" first="Marta L." last="Dediego">Marta L. Dediego</name>
<name sortKey="Ortega, Sandra" sort="Ortega, Sandra" uniqKey="Ortega S" first="Sandra" last="Ortega">Sandra Ortega</name>
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<country name="États-Unis"><region name="État de New York"><name sortKey="Yang, Hongmei" sort="Yang, Hongmei" uniqKey="Yang H" first="Hongmei" last="Yang">Hongmei Yang</name>
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