A single amino acid substitution in the S1 and S2 Spike protein domains determines the neutralization escape phenotype of SARS-CoV
Identifieur interne : 000E55 ( Pmc/Checkpoint ); précédent : 000E54; suivant : 000E56A single amino acid substitution in the S1 and S2 Spike protein domains determines the neutralization escape phenotype of SARS-CoV
Auteurs : Yu-Ya Mitsuki [Japon] ; Kazuo Ohnishi [Japon] ; Hirotaka Takagi [Japon] ; Masamichi Oshima [Japon] ; Takuya Yamamoto [Japon] ; Fuminori Mizukoshi [Japon] ; Kazutaka Terahara [Japon] ; Kazuo Kobayashi [Japon] ; Naoki Yamamoto [Japon] ; Shoji Yamaoka [Japon] ; Yasuko Tsunetsugu-Yokota [Japon]Source :
- Microbes and Infection [ 1286-4579 ] ; 2008.
Abstract
In response to SARS-CoV infection, neutralizing antibodies are generated against the Spike (S) protein. Determination of the active regions that allow viral escape from neutralization would enable the use of these antibodies for future passive immunotherapy. We immunized mice with UV-inactivated SARS-CoV to generate three anti-S monoclonal antibodies, and established several neutralization escape mutants with S protein. We identified several amino acid substitutions, including Y442F and V601G in the S1 domain and D757N and A834V in the S2 region. In the presence of each neutralizing antibody, double mutants with substitutions in both domains exhibited a greater growth advantage than those with only one substitution. Importantly, combining two monoclonal antibodies that target different epitopes effected almost complete suppression of wild type virus replication. Thus, for effective passive immunotherapy, it is important to use neutralizing antibodies that recognize both the S1 and S2 regions.
Url:
DOI: 10.1016/j.micinf.2008.05.009
PubMed: 18606245
PubMed Central: 7110505
Affiliations:
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id="aff3">AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Yamaoka, Shoji" sort="Yamaoka, Shoji" uniqKey="Yamaoka S" 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wicri:step="Checkpoint">000E55</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A single amino acid substitution in the S1 and S2 Spike protein domains determines the neutralization escape phenotype of SARS-CoV</title><author><name sortKey="Mitsuki, Yu Ya" sort="Mitsuki, Yu Ya" uniqKey="Mitsuki Y" first="Yu-Ya" last="Mitsuki">Yu-Ya Mitsuki</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Ohnishi, Kazuo" sort="Ohnishi, Kazuo" uniqKey="Ohnishi K" first="Kazuo" last="Ohnishi">Kazuo Ohnishi</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Takagi, Hirotaka" sort="Takagi, Hirotaka" uniqKey="Takagi H" first="Hirotaka" last="Takagi">Hirotaka Takagi</name><affiliation wicri:level="1"><nlm:aff id="aff2">Division of Biosafety Control and Research, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Biosafety Control and Research, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Oshima, Masamichi" sort="Oshima, Masamichi" uniqKey="Oshima M" first="Masamichi" last="Oshima">Masamichi Oshima</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Yamamoto, Takuya" sort="Yamamoto, Takuya" uniqKey="Yamamoto T" first="Takuya" last="Yamamoto">Takuya Yamamoto</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Mizukoshi, Fuminori" sort="Mizukoshi, Fuminori" uniqKey="Mizukoshi F" first="Fuminori" last="Mizukoshi">Fuminori Mizukoshi</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Terahara, Kazutaka" sort="Terahara, Kazutaka" uniqKey="Terahara K" first="Kazutaka" last="Terahara">Kazutaka Terahara</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Kobayashi, Kazuo" sort="Kobayashi, Kazuo" uniqKey="Kobayashi K" first="Kazuo" last="Kobayashi">Kazuo Kobayashi</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Yamamoto, Naoki" sort="Yamamoto, Naoki" uniqKey="Yamamoto N" first="Naoki" last="Yamamoto">Naoki Yamamoto</name><affiliation wicri:level="1"><nlm:aff id="aff3">AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Yamaoka, Shoji" sort="Yamaoka, Shoji" uniqKey="Yamaoka S" first="Shoji" last="Yamaoka">Shoji Yamaoka</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Tsunetsugu Yokota, Yasuko" sort="Tsunetsugu Yokota, Yasuko" uniqKey="Tsunetsugu Yokota Y" first="Yasuko" last="Tsunetsugu-Yokota">Yasuko Tsunetsugu-Yokota</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author></analytic><series><title level="j">Microbes and Infection</title><idno type="ISSN">1286-4579</idno><idno type="eISSN">1769-714X</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>In response to SARS-CoV infection, neutralizing antibodies are generated against the Spike (S) protein. Determination of the active regions that allow viral escape from neutralization would enable the use of these antibodies for future passive immunotherapy. We immunized mice with UV-inactivated SARS-CoV to generate three anti-S monoclonal antibodies, and established several neutralization escape mutants with S protein. We identified several amino acid substitutions, including Y442F and V601G in the S1 domain and D757N and A834V in the S2 region. In the presence of each neutralizing antibody, double mutants with substitutions in both domains exhibited a greater growth advantage than those with only one substitution. Importantly, combining two monoclonal antibodies that target different epitopes effected almost complete suppression of wild type virus replication. Thus, for effective passive immunotherapy, it is important to use neutralizing antibodies that recognize both the S1 and S2 regions.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Rota, P A" uniqKey="Rota P">P.A. Rota</name></author><author><name sortKey="Oberste, M S" uniqKey="Oberste M">M.S. Oberste</name></author><author><name sortKey="Monroe, S S" uniqKey="Monroe S">S.S. Monroe</name></author><author><name sortKey="Nix, W A" uniqKey="Nix W">W.A. Nix</name></author><author><name sortKey="Campagnoli, R" uniqKey="Campagnoli R">R. Campagnoli</name></author><author><name sortKey="Icenogle, J P" uniqKey="Icenogle J">J.P. Icenogle</name></author><author><name sortKey="Penaranda, S" uniqKey="Penaranda S">S. Penaranda</name></author><author><name sortKey="Bankamp, B" uniqKey="Bankamp B">B. Bankamp</name></author><author><name sortKey="Maher, K" uniqKey="Maher K">K. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Microbes Infect</journal-id><journal-id journal-id-type="iso-abbrev">Microbes Infect</journal-id><journal-title-group><journal-title>Microbes and Infection</journal-title></journal-title-group><issn pub-type="ppub">1286-4579</issn><issn pub-type="epub">1769-714X</issn><publisher><publisher-name>Elsevier Masson SAS.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">18606245</article-id><article-id pub-id-type="pmc">7110505</article-id><article-id pub-id-type="publisher-id">S1286-4579(08)00146-9</article-id><article-id pub-id-type="doi">10.1016/j.micinf.2008.05.009</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>A single amino acid substitution in the S1 and S2 Spike protein domains determines the neutralization escape phenotype of SARS-CoV</article-title></title-group><contrib-group><contrib contrib-type="author" id="au1"><name><surname>Mitsuki</surname><given-names>Yu-ya</given-names></name><xref rid="aff1" ref-type="aff">a</xref><xref rid="aff4" ref-type="aff">d</xref></contrib><contrib contrib-type="author" id="au2"><name><surname>Ohnishi</surname><given-names>Kazuo</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au3"><name><surname>Takagi</surname><given-names>Hirotaka</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au4"><name><surname>Oshima</surname><given-names>Masamichi</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au5"><name><surname>Yamamoto</surname><given-names>Takuya</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au6"><name><surname>Mizukoshi</surname><given-names>Fuminori</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au7"><name><surname>Terahara</surname><given-names>Kazutaka</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au8"><name><surname>Kobayashi</surname><given-names>Kazuo</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au9"><name><surname>Yamamoto</surname><given-names>Naoki</given-names></name><xref rid="aff3" ref-type="aff">c</xref><xref rid="aff4" ref-type="aff">d</xref></contrib><contrib contrib-type="author" id="au10"><name><surname>Yamaoka</surname><given-names>Shoji</given-names></name><xref rid="aff4" ref-type="aff">d</xref></contrib><contrib contrib-type="author" id="au11"><name><surname>Tsunetsugu-Yokota</surname><given-names>Yasuko</given-names></name><email>yyokota@nih.go.jp</email><xref rid="aff1" ref-type="aff">a</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib></contrib-group><aff id="aff1"><label>a</label>Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan</aff><aff id="aff2"><label>b</label>Division of Biosafety Control and Research, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan</aff><aff id="aff3"><label>c</label>AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan</aff><aff id="aff4"><label>d</label>Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author. Tel.: +81 3 5285 1111; fax: +81 3 5285 1150. <email>yyokota@nih.go.jp</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>19</day><month>6</month><year>2008</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><month>7</month><year>2008</year></pub-date><pub-date pub-type="epub"><day>19</day><month>6</month><year>2008</year></pub-date><volume>10</volume><issue>8</issue><fpage>908</fpage><lpage>915</lpage><history><date date-type="received"><day>14</day><month>1</month><year>2008</year></date><date date-type="accepted"><day>26</day><month>5</month><year>2008</year></date></history><permissions><copyright-statement>Copyright © 2008 Elsevier Masson SAS. All rights reserved.</copyright-statement><copyright-year>2008</copyright-year><copyright-holder>Elsevier Masson SAS</copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><abstract><p>In response to SARS-CoV infection, neutralizing antibodies are generated against the Spike (S) protein. Determination of the active regions that allow viral escape from neutralization would enable the use of these antibodies for future passive immunotherapy. We immunized mice with UV-inactivated SARS-CoV to generate three anti-S monoclonal antibodies, and established several neutralization escape mutants with S protein. We identified several amino acid substitutions, including Y442F and V601G in the S1 domain and D757N and A834V in the S2 region. In the presence of each neutralizing antibody, double mutants with substitutions in both domains exhibited a greater growth advantage than those with only one substitution. Importantly, combining two monoclonal antibodies that target different epitopes effected almost complete suppression of wild type virus replication. Thus, for effective passive immunotherapy, it is important to use neutralizing antibodies that recognize both the S1 and S2 regions.</p></abstract><kwd-group><title>Keywords</title><kwd>Escape mutants</kwd><kwd>Neutralizing antibody</kwd><kwd>Passive immunotherapy</kwd><kwd>SARS-CoV</kwd></kwd-group></article-meta></front></pmc><affiliations><list><country><li>Japon</li></country><region><li>Région de Kantō</li></region><settlement><li>Tokyo</li></settlement></list><tree><country name="Japon"><region name="Région de Kantō"><name sortKey="Mitsuki, Yu Ya" sort="Mitsuki, Yu Ya" uniqKey="Mitsuki Y" first="Yu-Ya" last="Mitsuki">Yu-Ya Mitsuki</name></region><name sortKey="Kobayashi, Kazuo" sort="Kobayashi, Kazuo" uniqKey="Kobayashi K" first="Kazuo" last="Kobayashi">Kazuo Kobayashi</name><name sortKey="Mitsuki, Yu Ya" sort="Mitsuki, Yu Ya" uniqKey="Mitsuki Y" first="Yu-Ya" last="Mitsuki">Yu-Ya Mitsuki</name><name sortKey="Mizukoshi, Fuminori" sort="Mizukoshi, Fuminori" uniqKey="Mizukoshi F" first="Fuminori" last="Mizukoshi">Fuminori Mizukoshi</name><name sortKey="Ohnishi, Kazuo" sort="Ohnishi, Kazuo" uniqKey="Ohnishi K" first="Kazuo" last="Ohnishi">Kazuo Ohnishi</name><name sortKey="Oshima, Masamichi" sort="Oshima, Masamichi" uniqKey="Oshima M" first="Masamichi" last="Oshima">Masamichi Oshima</name><name sortKey="Takagi, Hirotaka" sort="Takagi, Hirotaka" uniqKey="Takagi H" first="Hirotaka" last="Takagi">Hirotaka Takagi</name><name sortKey="Terahara, Kazutaka" sort="Terahara, Kazutaka" uniqKey="Terahara K" first="Kazutaka" last="Terahara">Kazutaka Terahara</name><name sortKey="Tsunetsugu Yokota, Yasuko" sort="Tsunetsugu Yokota, Yasuko" uniqKey="Tsunetsugu Yokota Y" first="Yasuko" last="Tsunetsugu-Yokota">Yasuko Tsunetsugu-Yokota</name><name sortKey="Yamamoto, Naoki" sort="Yamamoto, Naoki" uniqKey="Yamamoto N" first="Naoki" last="Yamamoto">Naoki Yamamoto</name><name sortKey="Yamamoto, Naoki" sort="Yamamoto, Naoki" uniqKey="Yamamoto N" first="Naoki" last="Yamamoto">Naoki Yamamoto</name><name sortKey="Yamamoto, Takuya" sort="Yamamoto, Takuya" uniqKey="Yamamoto T" first="Takuya" last="Yamamoto">Takuya Yamamoto</name><name sortKey="Yamaoka, Shoji" sort="Yamaoka, Shoji" uniqKey="Yamaoka S" first="Shoji" last="Yamaoka">Shoji Yamaoka</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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