Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses
Identifieur interne : 000B59 ( Main/Exploration ); précédent : 000B58; suivant : 000B60Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses
Auteurs : Björn F. Koel [Pays-Bas] ; Ramona Mögling [Pays-Bas, Royaume-Uni] ; Salin Chutinimitkul [Pays-Bas] ; Pieter L. Fraaij [Pays-Bas] ; David F. Burke [Royaume-Uni] ; Stefan Van Der Vliet [Pays-Bas] ; Emmie De Wit [Pays-Bas] ; Theo M. Bestebroer [Pays-Bas] ; Guus F. Rimmelzwaan [Pays-Bas] ; Albert D. M. E. Osterhaus [Pays-Bas] ; Derek J. Smith [Royaume-Uni, Pays-Bas] ; Ron A. M. Fouchier [Pays-Bas] ; Miranda De Graaf [Pays-Bas, Royaume-Uni]Source :
- Journal of Virology [ 0022-538X ] ; 2015.
Descripteurs français
- KwdFr :
- Analyse de mutations d'ADN, Animaux, Anticorps antiviraux (sang), Anticorps neutralisants (sang), Antigènes viraux (génétique), Antigènes viraux (immunologie), Dérive génétique, Déterminants antigéniques des lymphocytes B (immunologie), Furets, Glycoprotéine hémagglutinine du virus influenza (génétique), Glycoprotéine hémagglutinine du virus influenza (immunologie), Humains, Réplication virale, Sous-type H1N1 du virus de la grippe A (génétique), Sous-type H1N1 du virus de la grippe A (immunologie), Sous-type H1N1 du virus de la grippe A (physiologie), Substitution d'acide aminé, Variation des antigènes.
- MESH :
- génétique : Antigènes viraux, Glycoprotéine hémagglutinine du virus influenza, Sous-type H1N1 du virus de la grippe A.
- immunologie : Antigènes viraux, Déterminants antigéniques des lymphocytes B, Glycoprotéine hémagglutinine du virus influenza, Sous-type H1N1 du virus de la grippe A.
- physiologie : Sous-type H1N1 du virus de la grippe A.
- sang : Anticorps antiviraux, Anticorps neutralisants.
- Analyse de mutations d'ADN, Animaux, Dérive génétique, Furets, Humains, Réplication virale, Substitution d'acide aminé, Variation des antigènes.
English descriptors
- KwdEn :
- Amino Acid Substitution, Animals, Antibodies, Neutralizing (blood), Antibodies, Viral (blood), Antigenic Variation, Antigens, Viral (genetics), Antigens, Viral (immunology), DNA Mutational Analysis, Epitopes, B-Lymphocyte (immunology), Ferrets, Genetic Drift, Hemagglutinin Glycoproteins, Influenza Virus (genetics), Hemagglutinin Glycoproteins, Influenza Virus (immunology), Humans, Influenza A Virus, H1N1 Subtype (genetics), Influenza A Virus, H1N1 Subtype (immunology), Influenza A Virus, H1N1 Subtype (physiology), Virus Replication.
- MESH :
- chemical , blood : Antibodies, Neutralizing, Antibodies, Viral.
- chemical , genetics : Antigens, Viral, Hemagglutinin Glycoproteins, Influenza Virus.
- chemical , immunology : Antigens, Viral, Epitopes, B-Lymphocyte, Hemagglutinin Glycoproteins, Influenza Virus.
- genetics : Influenza A Virus, H1N1 Subtype.
- immunology : Influenza A Virus, H1N1 Subtype.
- physiology : Influenza A Virus, H1N1 Subtype.
- Amino Acid Substitution, Animals, Antigenic Variation, DNA Mutational Analysis, Ferrets, Genetic Drift, Humans, Virus Replication.
Abstract
The majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from neutralizing antibodies, affect viral fitness, and change receptor preference. In this study, we constructed mutants with substitutions in the hemagglutinin of A/Netherlands/602/09 in an attenuated backbone to explore amino acid changes that may contribute to emergence of antigenic variants in the human population. Our analysis revealed that single substitutions affecting the loop that consists of amino acid positions 151 to 159 located adjacent to the receptor binding site caused escape from ferret and human antibodies elicited after primary A(H1N1)pdm09 virus infection. The majority of these substitutions resulted in similar or increased replication efficiency
Url:
DOI: 10.1128/JVI.02962-14
PubMed: 25609810
PubMed Central: 4403388
Affiliations:
- Pays-Bas, Royaume-Uni
- Angleterre, Angleterre de l'Est, Hollande-Méridionale
- Cambridge, Rotterdam
- Université de Cambridge
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Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses</title>
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<author><name sortKey="Burke, David F" sort="Burke, David F" uniqKey="Burke D" first="David F." last="Burke">David F. Burke</name>
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<author><name sortKey="De Wit, Emmie" sort="De Wit, Emmie" uniqKey="De Wit E" first="Emmie" last="De Wit">Emmie De Wit</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Viroscience, Erasmus MC, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bestebroer, Theo M" sort="Bestebroer, Theo M" uniqKey="Bestebroer T" first="Theo M." last="Bestebroer">Theo M. Bestebroer</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Viroscience, Erasmus MC, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Viroscience, Erasmus MC, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><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 wicri:level="3"><nlm:aff id="aff1">Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Viroscience, Erasmus MC, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Smith, Derek J" sort="Smith, Derek J" uniqKey="Smith D" first="Derek J." last="Smith">Derek J. Smith</name>
<affiliation wicri:level="4"><nlm:aff id="aff2">Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="aff4">WHO Collaborating Centre for Modeling Evolution and Control of Emerging Infectious Diseases, University of Cambridge, Cambridge, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>WHO Collaborating Centre for Modeling Evolution and Control of Emerging Infectious Diseases, University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff1">Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Viroscience, Erasmus MC, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</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>
<affiliation wicri:level="3"><nlm:aff id="aff1">Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Viroscience, Erasmus MC, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="De Graaf, Miranda" sort="De Graaf, Miranda" uniqKey="De Graaf M" first="Miranda" last="De Graaf">Miranda De Graaf</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Viroscience, Erasmus MC, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="aff2">Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
<idno type="eISSN">1098-5514</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Substitution</term>
<term>Animals</term>
<term>Antibodies, Neutralizing (blood)</term>
<term>Antibodies, Viral (blood)</term>
<term>Antigenic Variation</term>
<term>Antigens, Viral (genetics)</term>
<term>Antigens, Viral (immunology)</term>
<term>DNA Mutational Analysis</term>
<term>Epitopes, B-Lymphocyte (immunology)</term>
<term>Ferrets</term>
<term>Genetic Drift</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (genetics)</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (immunology)</term>
<term>Humans</term>
<term>Influenza A Virus, H1N1 Subtype (genetics)</term>
<term>Influenza A Virus, H1N1 Subtype (immunology)</term>
<term>Influenza A Virus, H1N1 Subtype (physiology)</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de mutations d'ADN</term>
<term>Animaux</term>
<term>Anticorps antiviraux (sang)</term>
<term>Anticorps neutralisants (sang)</term>
<term>Antigènes viraux (génétique)</term>
<term>Antigènes viraux (immunologie)</term>
<term>Dérive génétique</term>
<term>Déterminants antigéniques des lymphocytes B (immunologie)</term>
<term>Furets</term>
<term>Glycoprotéine hémagglutinine du virus influenza (génétique)</term>
<term>Glycoprotéine hémagglutinine du virus influenza (immunologie)</term>
<term>Humains</term>
<term>Réplication virale</term>
<term>Sous-type H1N1 du virus de la grippe A (génétique)</term>
<term>Sous-type H1N1 du virus de la grippe A (immunologie)</term>
<term>Sous-type H1N1 du virus de la grippe A (physiologie)</term>
<term>Substitution d'acide aminé</term>
<term>Variation des antigènes</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Antigens, Viral</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antigens, Viral</term>
<term>Epitopes, B-Lymphocyte</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Influenza A Virus, H1N1 Subtype</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigènes viraux</term>
<term>Glycoprotéine hémagglutinine du virus influenza</term>
<term>Sous-type H1N1 du virus de la grippe A</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigènes viraux</term>
<term>Déterminants antigéniques des lymphocytes B</term>
<term>Glycoprotéine hémagglutinine du virus influenza</term>
<term>Sous-type H1N1 du virus de la grippe A</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Influenza A Virus, H1N1 Subtype</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Sous-type H1N1 du virus de la grippe A</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Influenza A Virus, H1N1 Subtype</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Anticorps antiviraux</term>
<term>Anticorps neutralisants</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Substitution</term>
<term>Animals</term>
<term>Antigenic Variation</term>
<term>DNA Mutational Analysis</term>
<term>Ferrets</term>
<term>Genetic Drift</term>
<term>Humans</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Analyse de mutations d'ADN</term>
<term>Animaux</term>
<term>Dérive génétique</term>
<term>Furets</term>
<term>Humains</term>
<term>Réplication virale</term>
<term>Substitution d'acide aminé</term>
<term>Variation des antigènes</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>ABSTRACT</title>
<p>The majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from neutralizing antibodies, affect viral fitness, and change receptor preference. In this study, we constructed mutants with substitutions in the hemagglutinin of A/Netherlands/602/09 in an attenuated backbone to explore amino acid changes that may contribute to emergence of antigenic variants in the human population. Our analysis revealed that single substitutions affecting the loop that consists of amino acid positions 151 to 159 located adjacent to the receptor binding site caused escape from ferret and human antibodies elicited after primary A(H1N1)pdm09 virus infection. The majority of these substitutions resulted in similar or increased replication efficiency <italic>in vitro</italic>
compared to that of the virus carrying the wild-type hemagglutinin and did not result in a change of receptor preference. However, none of the substitutions was sufficient for escape from the antibodies in sera from individuals that experienced both seasonal and pandemic A(H1N1) virus infections. These results suggest that antibodies directed against epitopes on seasonal A(H1N1) viruses contribute to neutralization of A(H1N1)pdm09 antigenic variants, thereby limiting the number of possible substitutions that could lead to escape from population immunity.
</p>
<p><bold>IMPORTANCE</bold>
Influenza A viruses can cause significant morbidity and mortality in humans. Amino acid substitutions in the hemagglutinin protein can result in escape from antibody-mediated neutralization. This allows the virus to reinfect individuals that have acquired immunity to previously circulating strains through infection or vaccination. To date, the vast majority of A(H1N1)pdm09 strains remain antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as a result of increasing population immunity. We show that single amino acid substitutions near the receptor binding site were sufficient to escape from antibodies specific for A(H1N1)pdm09 viruses but not from antibodies elicited in response to infections with seasonal A(H1N1) and A(H1N1)pdm09 viruses. This study identified substitutions in A(H1N1)pdm09 viruses that support escape from population immunity but also suggested that the number of potential escape variants is limited by previous exposure to seasonal A(H1N1) viruses.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>Pays-Bas</li>
<li>Royaume-Uni</li>
</country>
<region><li>Angleterre</li>
<li>Angleterre de l'Est</li>
<li>Hollande-Méridionale</li>
</region>
<settlement><li>Cambridge</li>
<li>Rotterdam</li>
</settlement>
<orgName><li>Université de Cambridge</li>
</orgName>
</list>
<tree><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Koel, Bjorn F" sort="Koel, Bjorn F" uniqKey="Koel B" first="Björn F." last="Koel">Björn F. Koel</name>
</region>
<name sortKey="Bestebroer, Theo M" sort="Bestebroer, Theo M" uniqKey="Bestebroer T" first="Theo M." last="Bestebroer">Theo M. Bestebroer</name>
<name sortKey="Chutinimitkul, Salin" sort="Chutinimitkul, Salin" uniqKey="Chutinimitkul S" first="Salin" last="Chutinimitkul">Salin Chutinimitkul</name>
<name sortKey="De Graaf, Miranda" sort="De Graaf, Miranda" uniqKey="De Graaf M" first="Miranda" last="De Graaf">Miranda De Graaf</name>
<name sortKey="De Wit, Emmie" sort="De Wit, Emmie" uniqKey="De Wit E" first="Emmie" last="De Wit">Emmie De Wit</name>
<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>
<name sortKey="Fraaij, Pieter L" sort="Fraaij, Pieter L" uniqKey="Fraaij P" first="Pieter L." last="Fraaij">Pieter L. Fraaij</name>
<name sortKey="Fraaij, Pieter L" sort="Fraaij, Pieter L" uniqKey="Fraaij P" first="Pieter L." last="Fraaij">Pieter L. Fraaij</name>
<name sortKey="Mogling, Ramona" sort="Mogling, Ramona" uniqKey="Mogling R" first="Ramona" last="Mögling">Ramona Mögling</name>
<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>
<name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name>
<name sortKey="Smith, Derek J" sort="Smith, Derek J" uniqKey="Smith D" first="Derek J." last="Smith">Derek J. Smith</name>
<name sortKey="Van Der Vliet, Stefan" sort="Van Der Vliet, Stefan" uniqKey="Van Der Vliet S" first="Stefan" last="Van Der Vliet">Stefan Van Der Vliet</name>
</country>
<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Mogling, Ramona" sort="Mogling, Ramona" uniqKey="Mogling R" first="Ramona" last="Mögling">Ramona Mögling</name>
</region>
<name sortKey="Burke, David F" sort="Burke, David F" uniqKey="Burke D" first="David F." last="Burke">David F. Burke</name>
<name sortKey="Burke, David F" sort="Burke, David F" uniqKey="Burke D" first="David F." last="Burke">David F. Burke</name>
<name sortKey="De Graaf, Miranda" sort="De Graaf, Miranda" uniqKey="De Graaf M" first="Miranda" last="De Graaf">Miranda De Graaf</name>
<name sortKey="Smith, Derek J" sort="Smith, Derek J" uniqKey="Smith D" first="Derek J." last="Smith">Derek J. Smith</name>
<name sortKey="Smith, Derek J" sort="Smith, Derek J" uniqKey="Smith D" first="Derek J." last="Smith">Derek J. Smith</name>
</country>
</tree>
</affiliations>
</record>
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