Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses
Identifieur interne : 001159 ( Main/Exploration ); précédent : 001158; suivant : 001160Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses
Auteurs : Jianhua Sui [États-Unis] ; William C. Hwang [États-Unis] ; Sandra Perez [États-Unis] ; Ge Wei [États-Unis] ; Daniel Aird [États-Unis] ; Li-Mei Chen [États-Unis] ; Eugenio Santelli [États-Unis] ; Boguslaw Stec [États-Unis] ; Greg Cadwell [États-Unis] ; Maryam Ali [États-Unis] ; Hongquan Wan [États-Unis] ; Akikazu Murakami [États-Unis] ; Anuradha Yammanuru [États-Unis] ; Thomas Han [États-Unis] ; Nancy J. Cox [États-Unis] ; Laurie A. Bankston [États-Unis] ; Ruben O. Donis [États-Unis] ; Robert C. Liddington [États-Unis] ; Wayne A. Marasco [États-Unis]Source :
- Nature Structural & Molecular Biology [ 1545-9993 ] ; 2009-03.
Abstract
Influenza virus remains a serious health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Here we used a human non-immune antibody phage-display library and the H5 hemagglutinin ectodomain to select ten neutralizing antibodies (nAbs) that were effective against all group 1 influenza viruses tested, including H5N1 'bird flu' and the H1N1 'Spanish flu'. The crystal structure of one such nAb bound to H5 shows that it blocks infection by inserting its heavy chain into a conserved pocket in the stem region, thus preventing membrane fusion. Nine of the nAbs employ the germline gene VH1-69, and all seem to use the same neutralizing mechanism. Our data further suggest that this region is recalcitrant to neutralization escape and that nAb-based immunotherapy is a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.
A group of neutralizing monoclonal antibodies (mAbs) targeting the influenza A hemagglutinin has been selected and characterized. Remarkably, these mAbs were able to neutralize a broad array of group 1 strains and could protect mice from infection when given prophylactically or therapeutically. The crystal structure of one such mAb in complex with hemagglutinin provides insight into its mechanism of neutralization and broad specificity.
Url:
DOI: 10.1038/nsmb.1566
Affiliations:
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Cox</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Influenza Division, Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, 1600 Clifton Road, Mail Stop G-16, Atlanta, Georgia 30333</wicri:regionArea><wicri:noRegion>Georgia 30333</wicri:noRegion></affiliation></author><author><name sortKey="Bankston, Laurie A" sort="Bankston, Laurie A" uniqKey="Bankston L" first="Laurie A" last="Bankston">Laurie A. Bankston</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037</wicri:regionArea><wicri:noRegion>California 92037</wicri:noRegion></affiliation></author><author><name sortKey="Donis, Ruben O" sort="Donis, Ruben O" uniqKey="Donis R" first="Ruben O" last="Donis">Ruben O. Donis</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Influenza Division, Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, 1600 Clifton Road, Mail Stop G-16, Atlanta, Georgia 30333</wicri:regionArea><wicri:noRegion>Georgia 30333</wicri:noRegion></affiliation><affiliation></affiliation></author><author><name sortKey="Liddington, Robert C" sort="Liddington, Robert C" uniqKey="Liddington R" first="Robert C" last="Liddington">Robert C. Liddington</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037</wicri:regionArea><wicri:noRegion>California 92037</wicri:noRegion></affiliation><affiliation></affiliation></author><author><name sortKey="Marasco, Wayne A" sort="Marasco, Wayne A" uniqKey="Marasco W" first="Wayne A" last="Marasco">Wayne A. Marasco</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute; Department of Medicine, Harvard Medical School, 44 Binney Street JFB 826, Boston, Massachusetts 02115</wicri:regionArea><wicri:noRegion>Massachusetts 02115</wicri:noRegion></affiliation><affiliation wicri:level="1"><country wicri:rule="url">États-Unis</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Nature Structural & Molecular Biology</title><idno type="ISSN">1545-9993</idno><idno type="eISSN">1545-9985</idno><imprint><publisher>Nature Publishing Group</publisher><date when="2009-03">2009-03</date><biblScope unit="vol">16</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="265">265</biblScope><biblScope unit="page" to="273">273</biblScope><date type="Copyright" when="2009">2009</date></imprint><idno type="ISSN">1545-9993</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1545-9993</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="eng">Influenza virus remains a serious health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Here we used a human non-immune antibody phage-display library and the H5 hemagglutinin ectodomain to select ten neutralizing antibodies (nAbs) that were effective against all group 1 influenza viruses tested, including H5N1 'bird flu' and the H1N1 'Spanish flu'. The crystal structure of one such nAb bound to H5 shows that it blocks infection by inserting its heavy chain into a conserved pocket in the stem region, thus preventing membrane fusion. Nine of the nAbs employ the germline gene VH1-69, and all seem to use the same neutralizing mechanism. Our data further suggest that this region is recalcitrant to neutralization escape and that nAb-based immunotherapy is a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.</div><div type="abstract" xml:lang="eng">A group of neutralizing monoclonal antibodies (mAbs) targeting the influenza A hemagglutinin has been selected and characterized. Remarkably, these mAbs were able to neutralize a broad array of group 1 strains and could protect mice from infection when given prophylactically or therapeutically. The crystal structure of one such mAb in complex with hemagglutinin provides insight into its mechanism of neutralization and broad specificity.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Sui, Jianhua" sort="Sui, Jianhua" uniqKey="Sui J" first="Jianhua" last="Sui">Jianhua Sui</name></noRegion><name sortKey="Aird, Daniel" sort="Aird, Daniel" uniqKey="Aird D" first="Daniel" last="Aird">Daniel Aird</name><name sortKey="Ali, Maryam" sort="Ali, Maryam" uniqKey="Ali M" first="Maryam" last="Ali">Maryam Ali</name><name sortKey="Bankston, Laurie A" sort="Bankston, Laurie A" uniqKey="Bankston L" first="Laurie A" last="Bankston">Laurie A. Bankston</name><name sortKey="Cadwell, Greg" sort="Cadwell, Greg" uniqKey="Cadwell G" first="Greg" last="Cadwell">Greg Cadwell</name><name sortKey="Chen, Li Mei" sort="Chen, Li Mei" uniqKey="Chen L" first="Li-Mei" last="Chen">Li-Mei Chen</name><name sortKey="Cox, Nancy J" sort="Cox, Nancy J" uniqKey="Cox N" first="Nancy J" last="Cox">Nancy J. Cox</name><name sortKey="Donis, Ruben O" sort="Donis, Ruben O" uniqKey="Donis R" first="Ruben O" last="Donis">Ruben O. Donis</name><name sortKey="Han, Thomas" sort="Han, Thomas" uniqKey="Han T" first="Thomas" last="Han">Thomas Han</name><name sortKey="Hwang, William C" sort="Hwang, William C" uniqKey="Hwang W" first="William C" last="Hwang">William C. Hwang</name><name sortKey="Liddington, Robert C" sort="Liddington, Robert C" uniqKey="Liddington R" first="Robert C" last="Liddington">Robert C. Liddington</name><name sortKey="Marasco, Wayne A" sort="Marasco, Wayne A" uniqKey="Marasco W" first="Wayne A" last="Marasco">Wayne A. Marasco</name><name sortKey="Marasco, Wayne A" sort="Marasco, Wayne A" uniqKey="Marasco W" first="Wayne A" last="Marasco">Wayne A. Marasco</name><name sortKey="Murakami, Akikazu" sort="Murakami, Akikazu" uniqKey="Murakami A" first="Akikazu" last="Murakami">Akikazu Murakami</name><name sortKey="Perez, Sandra" sort="Perez, Sandra" uniqKey="Perez S" first="Sandra" last="Perez">Sandra Perez</name><name sortKey="Santelli, Eugenio" sort="Santelli, Eugenio" uniqKey="Santelli E" first="Eugenio" last="Santelli">Eugenio Santelli</name><name sortKey="Stec, Boguslaw" sort="Stec, Boguslaw" uniqKey="Stec B" first="Boguslaw" last="Stec">Boguslaw Stec</name><name sortKey="Sui, Jianhua" sort="Sui, Jianhua" uniqKey="Sui J" first="Jianhua" last="Sui">Jianhua Sui</name><name sortKey="Wan, Hongquan" sort="Wan, Hongquan" uniqKey="Wan H" first="Hongquan" last="Wan">Hongquan Wan</name><name sortKey="Wei, Ge" sort="Wei, Ge" uniqKey="Wei G" first="Ge" last="Wei">Ge Wei</name><name sortKey="Yammanuru, Anuradha" sort="Yammanuru, Anuradha" uniqKey="Yammanuru A" first="Anuradha" last="Yammanuru">Anuradha Yammanuru</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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