Human antibody 3E1 targets the HA stem region of H1N1 and H5N6 influenza A viruses
Identifieur interne : 000444 ( Main/Exploration ); précédent : 000443; suivant : 000445Human antibody 3E1 targets the HA stem region of H1N1 and H5N6 influenza A viruses
Auteurs : Wenshuai Wang [République populaire de Chine] ; Xiaoyu Sun [République populaire de Chine] ; Yanbing Li [République populaire de Chine] ; Jinpeng Su [République populaire de Chine] ; Zhiyang Ling [République populaire de Chine] ; Tianlong Zhang [République populaire de Chine] ; Fang Wang [République populaire de Chine] ; Hong Zhang [République populaire de Chine] ; Hualan Chen [République populaire de Chine] ; Jianping Ding [République populaire de Chine] ; Bing Sun [République populaire de Chine]Source :
- Nature Communications [ 2041-1723 ] ; 2016.
Abstract
As influenza A viruses remain a major threat to human health worldwide, the discovery of broadly neutralizing monoclonal antibodies that recognize conserved epitopes would facilitate the development of antibody-based therapeutic strategies. Here we report that a VH4-4-encoded human mAb named 3E1 could neutralize H1 and H5 subtype viruses
Url:
DOI: 10.1038/ncomms13577
PubMed: 27910950
PubMed Central: 5477490
Affiliations:
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Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences and University of Chinese Academy of Sciences, Chinese Academy of Sciences</institution>, 320 Yue-Yang Road, Shanghai 200031,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Shanghai Science Research Center, Chinese Academy of Sciences</institution>, Shanghai 201204,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sun, Bing" sort="Sun, Bing" uniqKey="Sun B" first="Bing" last="Sun">Bing Sun</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences</institution>, 320 Yue-Yang Road, Shanghai 200031,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a4"><institution>State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences</institution>, 320 Yue-Yang Road, Shanghai 200031,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27910950</idno><idno type="pmc">5477490</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477490</idno><idno 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viruses</title><author><name sortKey="Wang, Wenshuai" sort="Wang, Wenshuai" uniqKey="Wang W" first="Wenshuai" last="Wang">Wenshuai Wang</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences and University of Chinese Academy of Sciences, Chinese Academy of Sciences</institution>, 320 Yue-Yang Road, Shanghai 200031,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sun, Xiaoyu" sort="Sun, Xiaoyu" uniqKey="Sun X" first="Xiaoyu" last="Sun">Xiaoyu Sun</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences</institution>, 320 Yue-Yang Road, Shanghai 200031,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Li, Yanbing" sort="Li, Yanbing" uniqKey="Li Y" first="Yanbing" last="Li">Yanbing Li</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences</institution>, Harbin 150001,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Su, Jinpeng" sort="Su, Jinpeng" uniqKey="Su J" first="Jinpeng" last="Su">Jinpeng Su</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences</institution>, 320 Yue-Yang Road, Shanghai 200031,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ling, Zhiyang" sort="Ling, Zhiyang" uniqKey="Ling Z" first="Zhiyang" last="Ling">Zhiyang Ling</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences</institution>, 320 Yue-Yang Road, Shanghai 200031,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Tianlong" sort="Zhang, Tianlong" uniqKey="Zhang T" first="Tianlong" last="Zhang">Tianlong Zhang</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences and University of Chinese Academy of Sciences, Chinese Academy of Sciences</institution>, 320 Yue-Yang Road, Shanghai 200031,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Fang" sort="Wang, Fang" uniqKey="Wang F" first="Fang" last="Wang">Fang Wang</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences and University of Chinese Academy of Sciences, Chinese Academy of Sciences</institution>, 320 Yue-Yang Road, Shanghai 200031,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Hong" sort="Zhang, Hong" uniqKey="Zhang H" first="Hong" last="Zhang">Hong Zhang</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences</institution>, 320 Yue-Yang Road, Shanghai 200031,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Hualan" sort="Chen, Hualan" uniqKey="Chen H" first="Hualan" last="Chen">Hualan Chen</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences</institution>, Harbin 150001,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ding, Jianping" sort="Ding, Jianping" uniqKey="Ding J" first="Jianping" last="Ding">Jianping Ding</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences and University of Chinese Academy of Sciences, Chinese Academy of Sciences</institution>, 320 Yue-Yang Road, Shanghai 200031,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Shanghai Science Research Center, Chinese Academy of Sciences</institution>, Shanghai 201204,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sun, Bing" sort="Sun, Bing" uniqKey="Sun B" first="Bing" last="Sun">Bing Sun</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences</institution>, 320 Yue-Yang Road, Shanghai 200031,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a4"><institution>State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences</institution>, 320 Yue-Yang Road, Shanghai 200031,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>As influenza A viruses remain a major threat to human health worldwide, the discovery of broadly neutralizing monoclonal antibodies that recognize conserved epitopes would facilitate the development of antibody-based therapeutic strategies. Here we report that a V<sub>H</sub>4-4-encoded human mAb named 3E1 could neutralize H1 and H5 subtype viruses <italic>in vitro</italic> and protect mice against the H1N1 and H5N6 viruses by inhibiting the low pH-induced conformational rearrangement of haemagglutinin (HA), hence blocking membrane fusion. The crystal structures of 3E1 Fab in complex with HA of two H1N1 strains reveal that 3E1, with both heavy and light chains, binds to a conserved epitope of the HA stem region, comprising parts of the fusion peptide, the F subdomain and the outermost β-strand preceding helix A. Altogether, these data suggest the potential of 3E1 as a therapeutic drug against H1 and H5 subtype viruses.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Medina, R A" uniqKey="Medina R">R. A. Medina</name></author><author><name sortKey="Garcia Sastre, A" uniqKey="Garcia Sastre A">A. 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Higgins</name></author><author><name sortKey="Sharp, P M" uniqKey="Sharp P">P. M. Sharp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rowe, T" uniqKey="Rowe T">T. Rowe</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Wang, Wenshuai" sort="Wang, Wenshuai" uniqKey="Wang W" first="Wenshuai" last="Wang">Wenshuai Wang</name></noRegion><name sortKey="Chen, Hualan" sort="Chen, Hualan" uniqKey="Chen H" first="Hualan" last="Chen">Hualan Chen</name><name sortKey="Ding, Jianping" sort="Ding, Jianping" uniqKey="Ding J" first="Jianping" last="Ding">Jianping Ding</name><name sortKey="Ding, Jianping" sort="Ding, Jianping" uniqKey="Ding J" first="Jianping" last="Ding">Jianping Ding</name><name sortKey="Li, Yanbing" sort="Li, Yanbing" uniqKey="Li Y" first="Yanbing" last="Li">Yanbing Li</name><name sortKey="Ling, Zhiyang" sort="Ling, Zhiyang" uniqKey="Ling Z" first="Zhiyang" last="Ling">Zhiyang Ling</name><name sortKey="Su, Jinpeng" sort="Su, Jinpeng" uniqKey="Su J" first="Jinpeng" last="Su">Jinpeng Su</name><name sortKey="Sun, Bing" sort="Sun, Bing" uniqKey="Sun B" first="Bing" last="Sun">Bing Sun</name><name sortKey="Sun, Bing" sort="Sun, Bing" uniqKey="Sun B" first="Bing" last="Sun">Bing Sun</name><name sortKey="Sun, Xiaoyu" sort="Sun, Xiaoyu" uniqKey="Sun X" first="Xiaoyu" last="Sun">Xiaoyu Sun</name><name sortKey="Wang, Fang" sort="Wang, Fang" uniqKey="Wang F" first="Fang" last="Wang">Fang Wang</name><name sortKey="Zhang, Hong" sort="Zhang, Hong" uniqKey="Zhang H" first="Hong" last="Zhang">Hong Zhang</name><name sortKey="Zhang, Tianlong" sort="Zhang, Tianlong" uniqKey="Zhang T" first="Tianlong" last="Zhang">Tianlong Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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