Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 virus
Identifieur interne : 000716 ( Main/Exploration ); précédent : 000715; suivant : 000717Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 virus
Auteurs : Martin Linster [Pays-Bas] ; Sander Van Boheemen [Pays-Bas] ; Miranda De Graaf [Pays-Bas] ; Eefje J. A. Schrauwen [Pays-Bas] ; Pascal Lexmond [Pays-Bas] ; Benjamin M Nz [Pays-Bas] ; Theo M. Bestebroer [Pays-Bas] ; Jan Baumann [Allemagne] ; Debby Van Riel [Pays-Bas] ; Guus F. Rimmelzwaan [Pays-Bas] ; Albert D. M. E. Osterhaus [Pays-Bas] ; Mikhail Matrosovich [Allemagne] ; Ron A. M. Fouchier [Pays-Bas] ; Sander Herfst [Pays-Bas]Source :
- Cell [ 0092-8674 ] ; 2014.
Abstract
Recently, A/H5N1 influenza viruses were shown to acquire airborne transmissibility between ferrets upon targeted mutagenesis and virus passage. The critical genetic changes in airborne A/Indonesia/5/05 were not yet identified. Here, five substitutions proved to be sufficient to determine this airborne transmission phenotype. Substitutions in PB1 and PB2 collectively caused enhanced transcription and virus replication. One substitution increased HA thermostability and lowered the pH of membrane fusion. Two substitutions independently changed HA binding preference from α2,3 linked to α2,6 linked sialic acid receptors. The loss of a glycosylation site in HA enhanced overall binding to receptors. The acquired substitutions emerged early during ferret passage as minor variants and became dominant rapidly. Identification of substitutions that are essential for airborne transmission of avian influenza viruses between ferrets and their associated phenotypes advances our fundamental understanding of virus transmission and will increase the value of future surveillance programs and public health risk assessments.
Url:
DOI: 10.1016/j.cell.2014.02.040
PubMed: 24725402
PubMed Central: 4003409
Affiliations:
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A." last="Schrauwen">Eefje J. A. Schrauwen</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Lexmond, Pascal" sort="Lexmond, Pascal" uniqKey="Lexmond P" first="Pascal" last="Lexmond">Pascal Lexmond</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="M Nz, Benjamin" sort="M Nz, Benjamin" uniqKey="M Nz B" first="Benjamin" last="M Nz">Benjamin M Nz</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE 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="1"><nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Baumann, Jan" sort="Baumann, Jan" uniqKey="Baumann J" first="Jan" last="Baumann">Jan Baumann</name><affiliation wicri:level="3"><nlm:aff id="A2">Institute of Virology, Philipps-University, 35043 Marburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Philipps-University, 35043 Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation></author><author><name sortKey="Van Riel, Debby" sort="Van Riel, Debby" uniqKey="Van Riel D" first="Debby" last="Van Riel">Debby Van Riel</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE 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="1"><nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE 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="1"><nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Matrosovich, Mikhail" sort="Matrosovich, Mikhail" uniqKey="Matrosovich M" first="Mikhail" last="Matrosovich">Mikhail Matrosovich</name><affiliation wicri:level="3"><nlm:aff id="A2">Institute of Virology, Philipps-University, 35043 Marburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Philipps-University, 35043 Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></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="1"><nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Herfst, Sander" sort="Herfst, Sander" uniqKey="Herfst S" first="Sander" last="Herfst">Sander Herfst</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author></analytic><series><title level="j">Cell</title><idno type="ISSN">0092-8674</idno><idno type="eISSN">1097-4172</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>SUMMARY</title><p id="P3">Recently, A/H5N1 influenza viruses were shown to acquire airborne transmissibility between ferrets upon targeted mutagenesis and virus passage. The critical genetic changes in airborne A/Indonesia/5/05 were not yet identified. Here, five substitutions proved to be sufficient to determine this airborne transmission phenotype. Substitutions in PB1 and PB2 collectively caused enhanced transcription and virus replication. One substitution increased HA thermostability and lowered the pH of membrane fusion. Two substitutions independently changed HA binding preference from α2,3 linked to α2,6 linked sialic acid receptors. The loss of a glycosylation site in HA enhanced overall binding to receptors. The acquired substitutions emerged early during ferret passage as minor variants and became dominant rapidly. Identification of substitutions that are essential for airborne transmission of avian influenza viruses between ferrets and their associated phenotypes advances our fundamental understanding of virus transmission and will increase the value of future surveillance programs and public health risk assessments.</p></div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Pays-Bas</li></country><region><li>District de Giessen</li><li>Hesse (Land)</li><li>Hollande-Méridionale</li></region><settlement><li>Marbourg</li><li>Rotterdam</li></settlement></list><tree><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Linster, Martin" sort="Linster, Martin" uniqKey="Linster M" first="Martin" last="Linster">Martin Linster</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="De Graaf, Miranda" sort="De Graaf, Miranda" uniqKey="De Graaf M" first="Miranda" last="De Graaf">Miranda De Graaf</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="Herfst, Sander" sort="Herfst, Sander" uniqKey="Herfst S" first="Sander" last="Herfst">Sander Herfst</name><name sortKey="Lexmond, Pascal" sort="Lexmond, Pascal" uniqKey="Lexmond P" first="Pascal" last="Lexmond">Pascal Lexmond</name><name sortKey="M Nz, Benjamin" sort="M Nz, Benjamin" uniqKey="M Nz B" first="Benjamin" last="M Nz">Benjamin M Nz</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="Schrauwen, Eefje J A" sort="Schrauwen, Eefje J A" uniqKey="Schrauwen E" first="Eefje J. A." last="Schrauwen">Eefje J. A. Schrauwen</name><name sortKey="Van Boheemen, Sander" sort="Van Boheemen, Sander" uniqKey="Van Boheemen S" first="Sander" last="Van Boheemen">Sander Van Boheemen</name><name sortKey="Van Riel, Debby" sort="Van Riel, Debby" uniqKey="Van Riel D" first="Debby" last="Van Riel">Debby Van Riel</name></country><country name="Allemagne"><region name="Hesse (Land)"><name sortKey="Baumann, Jan" sort="Baumann, Jan" uniqKey="Baumann J" first="Jan" last="Baumann">Jan Baumann</name></region><name sortKey="Matrosovich, Mikhail" sort="Matrosovich, Mikhail" uniqKey="Matrosovich M" first="Mikhail" last="Matrosovich">Mikhail Matrosovich</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 virus
}}
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