Natural and directed antigenic drift of the H1 influenza virus hemagglutinin stalk domain
Identifieur interne : 000E27 ( Ncbi/Curation ); précédent : 000E26; suivant : 000E28Natural 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
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Christopher S. Anderson<affiliation><nlm:aff id="Aff1">David H. Smith Center for Vaccine Biology and Immunology, and Department of Microbiology and Immunology, Rochester, NY United States</nlm:aff>
<wicri:noCountry code="subfield">NY United States</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff1">David H. Smith Center for Vaccine Biology and Immunology, and Department of Microbiology and Immunology, Rochester, NY United States</nlm:aff>
<wicri:noCountry code="subfield">NY United States</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff1">David H. Smith Center for Vaccine Biology and Immunology, and Department of Microbiology and Immunology, Rochester, NY United States</nlm:aff>
<wicri:noCountry code="subfield">NY United States</wicri:noCountry>
</affiliation>
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<wicri:noCountry code="subfield">NY United States</wicri:noCountry>
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<wicri:noCountry code="subfield">NY United States</wicri:noCountry>
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<wicri:noCountry code="subfield">NY United States</wicri:noCountry>
</affiliation>
Le document en format XML
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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>
<author><name sortKey="Anderson, Christopher S" sort="Anderson, Christopher S" uniqKey="Anderson C" first="Christopher S." last="Anderson">Christopher S. Anderson</name>
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<author><name sortKey="Ortega, Sandra" sort="Ortega, Sandra" uniqKey="Ortega S" first="Sandra" last="Ortega">Sandra Ortega</name>
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<author><name sortKey="Chaves, Francisco A" sort="Chaves, Francisco A" uniqKey="Chaves F" first="Francisco A." last="Chaves">Francisco A. Chaves</name>
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<author><name sortKey="Clark, Amelia M" sort="Clark, Amelia M" uniqKey="Clark A" first="Amelia M." last="Clark">Amelia M. Clark</name>
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<series><title level="j">Scientific Reports</title>
<idno type="eISSN">2045-2322</idno>
<imprint><date when="2017">2017</date>
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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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