A single amino acid substitution in the Sl and S2 Spike protein domains determines the neutralization escape phenotype of SARS-CoV
Identifieur interne : 000299 ( PascalFrancis/Checkpoint ); précédent : 000298; suivant : 000300A single amino acid substitution in the Sl 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.
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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.
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Pascal:08-0451539Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">A single amino acid substitution in the Sl 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>
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<author><name sortKey="Ohnishi, Kazuo" sort="Ohnishi, Kazuo" uniqKey="Ohnishi K" first="Kazuo" last="Ohnishi">Kazuo Ohnishi</name>
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<author><name sortKey="Takagi, Hirotaka" sort="Takagi, Hirotaka" uniqKey="Takagi H" first="Hirotaka" last="Takagi">Hirotaka Takagi</name>
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<author><name sortKey="Oshima, Masamichi" sort="Oshima, Masamichi" uniqKey="Oshima M" first="Masamichi" last="Oshima">Masamichi Oshima</name>
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<author><name sortKey="Yamamoto, Takuya" sort="Yamamoto, Takuya" uniqKey="Yamamoto T" first="Takuya" last="Yamamoto">Takuya Yamamoto</name>
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<author><name sortKey="Mizukoshi, Fuminori" sort="Mizukoshi, Fuminori" uniqKey="Mizukoshi F" first="Fuminori" last="Mizukoshi">Fuminori Mizukoshi</name>
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<author><name sortKey="Terahara, Kazutaka" sort="Terahara, Kazutaka" uniqKey="Terahara K" first="Kazutaka" last="Terahara">Kazutaka Terahara</name>
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<author><name sortKey="Kobayashi, Kazuo" sort="Kobayashi, Kazuo" uniqKey="Kobayashi K" first="Kazuo" last="Kobayashi">Kazuo Kobayashi</name>
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<author><name sortKey="Yamamoto, Naoki" sort="Yamamoto, Naoki" uniqKey="Yamamoto N" first="Naoki" last="Yamamoto">Naoki Yamamoto</name>
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<author><name sortKey="Yamaoka, Shoji" sort="Yamaoka, Shoji" uniqKey="Yamaoka S" first="Shoji" last="Yamaoka">Shoji Yamaoka</name>
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<author><name sortKey="Tsunetsugu Yokota, Yasuko" sort="Tsunetsugu Yokota, Yasuko" uniqKey="Tsunetsugu Yokota Y" first="Yasuko" last="Tsunetsugu-Yokota">Yasuko Tsunetsugu-Yokota</name>
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<series><title level="j" type="main">Microbes and infection</title>
<title level="j" type="abbreviated">Microbes infect.</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Immunotherapy</term>
<term>Mutation</term>
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<term>Protein</term>
<term>Severe acute respiratory syndrome virus</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Virus syndrome respiratoire aigu sévère</term>
<term>Protéine</term>
<term>Neutralisation</term>
<term>Phénotype</term>
<term>Mutation</term>
<term>Anticorps neutralisant</term>
<term>Immunothérapie</term>
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<front><div type="abstract" xml:lang="en">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.</div>
</front>
</TEI>
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<fA03 i2="1"><s0>Microbes infect.</s0>
</fA03>
<fA05><s2>10</s2>
</fA05>
<fA06><s2>8</s2>
</fA06>
<fA08 i1="01" i2="1" l="ENG"><s1>A single amino acid substitution in the Sl and S2 Spike protein domains determines the neutralization escape phenotype of SARS-CoV</s1>
</fA08>
<fA11 i1="01" i2="1"><s1>MITSUKI (Yu-Ya)</s1>
</fA11>
<fA11 i1="02" i2="1"><s1>OHNISHI (Kazuo)</s1>
</fA11>
<fA11 i1="03" i2="1"><s1>TAKAGI (Hirotaka)</s1>
</fA11>
<fA11 i1="04" i2="1"><s1>OSHIMA (Masamichi)</s1>
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<fA11 i1="05" i2="1"><s1>YAMAMOTO (Takuya)</s1>
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<fA11 i1="06" i2="1"><s1>MIZUKOSHI (Fuminori)</s1>
</fA11>
<fA11 i1="07" i2="1"><s1>TERAHARA (Kazutaka)</s1>
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<fA11 i1="08" i2="1"><s1>KOBAYASHI (Kazuo)</s1>
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<fA11 i1="09" i2="1"><s1>YAMAMOTO (Naoki)</s1>
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<fA11 i1="10" i2="1"><s1>YAMAOKA (Shoji)</s1>
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<fA11 i1="11" i2="1"><s1>TSUNETSUGU-YOKOTA (Yasuko)</s1>
</fA11>
<fA14 i1="01"><s1>Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1</s1>
<s2>Shinjuku-ku, Tokyo 162-8640</s2>
<s3>JPN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>11 aut.</sZ>
</fA14>
<fA14 i1="02"><s1>Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University</s1>
<s2>Tokyo 113-8519</s2>
<s3>JPN</s3>
<sZ>1 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</fA14>
<fA14 i1="03"><s1>Division of Biosafety Control and Research, National Institute of Infectious Diseases</s1>
<s2>Shinjuku-ku, Tokyo 162-8640</s2>
<s3>JPN</s3>
<sZ>3 aut.</sZ>
</fA14>
<fA14 i1="04"><s1>AIDS Research Center, National Institute of Infectious Diseases</s1>
<s2>Shinjuku-ku, Tokyo 162-8640</s2>
<s3>JPN</s3>
<sZ>9 aut.</sZ>
</fA14>
<fA20><s1>908-915</s1>
</fA20>
<fA21><s1>2008</s1>
</fA21>
<fA23 i1="01"><s0>ENG</s0>
</fA23>
<fA43 i1="01"><s1>INIST</s1>
<s2>26816</s2>
<s5>354000196570640090</s5>
</fA43>
<fA44><s0>0000</s0>
<s1>© 2008 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45><s0>28 ref.</s0>
</fA45>
<fA47 i1="01" i2="1"><s0>08-0451539</s0>
</fA47>
<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
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<fA66 i1="01"><s0>FRA</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>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.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002A05</s0>
</fC02>
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<s2>NW</s2>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Severe acute respiratory syndrome virus</s0>
<s2>NW</s2>
<s5>01</s5>
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<s5>01</s5>
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<s5>05</s5>
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<s5>05</s5>
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<s5>07</s5>
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<s5>07</s5>
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<s5>07</s5>
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<s5>08</s5>
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<fC03 i1="05" i2="X" l="ENG"><s0>Mutation</s0>
<s5>08</s5>
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<s5>08</s5>
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<s5>09</s5>
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<s5>10</s5>
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<s2>NW</s2>
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<s2>NW</s2>
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<s2>NW</s2>
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<fC07 i1="02" i2="X" l="SPA"><s0>Coronaviridae</s0>
<s2>NW</s2>
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<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Nidovirales</s0>
<s2>NW</s2>
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<fC07 i1="03" i2="X" l="SPA"><s0>Nidovirales</s0>
<s2>NW</s2>
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<s2>NW</s2>
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<s2>NW</s2>
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<s2>NW</s2>
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<fN21><s1>294</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
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<fN82><s1>OTO</s1>
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<affiliations><list><country><li>Japon</li>
</country>
<region><li>Région de Kantō</li>
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<settlement><li>Tokyo</li>
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<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>
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