Recurring and Adaptable Binding Motifs in Broadly Neutralizing Antibodies to Influenza Virus Are Encoded on the D3-9 Segment of the Ig Gene
Identifieur interne : 000162 ( Main/Exploration ); précédent : 000161; suivant : 000163Recurring and Adaptable Binding Motifs in Broadly Neutralizing Antibodies to Influenza Virus Are Encoded on the D3-9 Segment of the Ig Gene
Auteurs : Nicholas C. Wu [États-Unis] ; Seiya Yamayoshi [Japon] ; Mutsumi Ito [Japon] ; Ryuta Uraki [Japon] ; Yoshihiro Kawaoka [Japon, États-Unis] ; Ian A. Wilson [États-Unis]Source :
- Cell Host & Microbe [ 1931-3128 ] ; 2018.
Abstract
Discovery and characterization of broadly neutralizing antibodies (bnAbs) to the influenza hemagglutinin (HA) stem have provided insights for the development of a universal flu vaccine. Identification of signature features common to bnAbs from different individuals will be key to guiding immunogen design. S9-3-37 is a bnAb isolated from a healthy H5N1 vaccinee. Here, structural characterization reveals that the D3-9 gene segment of S9-3-37 contributes most of the interaction surface with the highly conserved stem epitope on HA. Comparison with other influenza bnAb crystal structures indicates that the D3-9 segment provides a general mechanism for targeting HA stem. Interestingly, such bnAbs can approach the HA stem with vastly different angles and orientations. Moreover, D3-9 can be translated in different reading frames in different bnAbs yet still target the same HA stem pocket. Thus, the D3-9 gene segment in the human immune repertoire can provide a robust defense against influenza virus.
Url:
DOI: 10.1016/j.chom.2018.09.010
PubMed: 30308159
PubMed Central: 6327842
Affiliations:
- Japon, États-Unis
- Californie, Région de Kantō, Wisconsin
- Madison (Wisconsin), Tokyo
- Université de Tokyo, Université du Wisconsin à Madison
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Wu</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Yamayoshi, Seiya" sort="Yamayoshi, Seiya" uniqKey="Yamayoshi S" first="Seiya" last="Yamayoshi">Seiya Yamayoshi</name><affiliation wicri:level="4"><nlm:aff id="aff2">Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName><placeName><settlement type="city">Tokyo</settlement><region type="province">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Ito, Mutsumi" sort="Ito, Mutsumi" uniqKey="Ito M" first="Mutsumi" last="Ito">Mutsumi Ito</name><affiliation wicri:level="4"><nlm:aff id="aff2">Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName><placeName><settlement type="city">Tokyo</settlement><region type="province">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Uraki, Ryuta" sort="Uraki, Ryuta" uniqKey="Uraki R" first="Ryuta" last="Uraki">Ryuta Uraki</name><affiliation wicri:level="4"><nlm:aff id="aff2">Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName><placeName><settlement type="city">Tokyo</settlement><region type="province">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><affiliation wicri:level="4"><nlm:aff id="aff2">Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName><placeName><settlement type="city">Tokyo</settlement><region type="province">Région de Kantō</region></placeName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName><orgName type="university" n="3">Université du Wisconsin à Madison</orgName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff3">Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName><orgName type="university" n="3">Université du Wisconsin à Madison</orgName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff4">Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName><placeName><settlement type="city">Tokyo</settlement><region type="province">Région de Kantō</region></placeName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName><orgName type="university" n="3">Université du Wisconsin à Madison</orgName></affiliation></author><author><name sortKey="Wilson, Ian A" sort="Wilson, Ian A" uniqKey="Wilson I" first="Ian A." last="Wilson">Ian A. Wilson</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff5">The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author></analytic><series><title level="j">Cell Host & Microbe</title><idno type="ISSN">1931-3128</idno><idno type="eISSN">1934-6069</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><p>Discovery and characterization of broadly neutralizing antibodies (bnAbs) to the influenza hemagglutinin (HA) stem have provided insights for the development of a universal flu vaccine. Identification of signature features common to bnAbs from different individuals will be key to guiding immunogen design. S9-3-37 is a bnAb isolated from a healthy H5N1 vaccinee. Here, structural characterization reveals that the D3-9 gene segment of S9-3-37 contributes most of the interaction surface with the highly conserved stem epitope on HA. Comparison with other influenza bnAb crystal structures indicates that the D3-9 segment provides a general mechanism for targeting HA stem. Interestingly, such bnAbs can approach the HA stem with vastly different angles and orientations. Moreover, D3-9 can be translated in different reading frames in different bnAbs yet still target the same HA stem pocket. Thus, the D3-9 gene segment in the human immune repertoire can provide a robust defense against influenza virus.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Al Lazikani, B" uniqKey="Al Lazikani B">B. 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Wilson</name></country><country name="Japon"><region name="Région de Kantō"><name sortKey="Yamayoshi, Seiya" sort="Yamayoshi, Seiya" uniqKey="Yamayoshi S" first="Seiya" last="Yamayoshi">Seiya Yamayoshi</name></region><name sortKey="Ito, Mutsumi" sort="Ito, Mutsumi" uniqKey="Ito M" first="Mutsumi" last="Ito">Mutsumi Ito</name><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><name sortKey="Uraki, Ryuta" sort="Uraki, Ryuta" uniqKey="Uraki R" first="Ryuta" last="Uraki">Ryuta Uraki</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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