A single amino acid substitution in the Sl and S2 Spike protein domains determines the neutralization escape phenotype of SARS-CoV
Identifieur interne : 003519 ( Main/Exploration ); précédent : 003518; suivant : 003520A 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.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (immunologie), Anticorps monoclonaux (immunologie), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (génétique), Glycoprotéines membranaires (immunologie), Mutation faux-sens, Méthode des plages virales, Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (immunologie), Réplication virale (immunologie), Souris, Structure tertiaire des protéines, Substitution d'acide aminé (génétique), Substitution d'acide aminé (immunologie), Tests de neutralisation, Virus du SRAS (croissance et développement), Virus du SRAS (génétique), Virus du SRAS (immunologie).
- MESH :
- croissance et développement : Virus du SRAS.
- génétique : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Substitution d'acide aminé, Virus du SRAS.
- immunologie : Anticorps antiviraux, Anticorps monoclonaux, Glycoprotéines membranaires, Protéines de l'enveloppe virale, Réplication virale, Substitution d'acide aminé, Virus du SRAS.
- Pascal (Inist)
English descriptors
- KwdEn :
- Amino Acid Substitution (genetics), Amino Acid Substitution (immunology), Animals, Antibodies, Monoclonal (immunology), Antibodies, Viral (immunology), Immunotherapy, Membrane Glycoproteins (genetics), Membrane Glycoproteins (immunology), Mice, Mutation, Mutation, Missense, Neutralization, Neutralization Tests, Neutralizing antibody, Phenotype, Protein, Protein Structure, Tertiary, SARS Virus (genetics), SARS Virus (growth & development), SARS Virus (immunology), Severe acute respiratory syndrome virus, Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (genetics), Viral Envelope Proteins (immunology), Viral Plaque Assay, Virus Replication (immunology).
- MESH :
- chemical , genetics : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , immunology : Antibodies, Monoclonal, Antibodies, Viral, Membrane Glycoproteins, Viral Envelope Proteins.
- genetics : Amino Acid Substitution, SARS Virus.
- growth & development : SARS Virus.
- immunology : Amino Acid Substitution, SARS Virus, Virus Replication.
- Animals, Mice, Mutation, Missense, Neutralization Tests, Protein Structure, Tertiary, Spike Glycoprotein, Coronavirus, Viral Plaque Assay.
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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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><affiliation wicri:level="1"><inist: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></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation><affiliation wicri:level="1"><inist: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></inist:fA14><country>Japon</country><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"><inist: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></inist:fA14><country>Japon</country><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"><inist: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></inist:fA14><country>Japon</country><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"><inist: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></inist:fA14><country>Japon</country><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"><inist: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></inist:fA14><country>Japon</country><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"><inist: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></inist:fA14><country>Japon</country><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"><inist: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></inist:fA14><country>Japon</country><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"><inist: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></inist:fA14><country>Japon</country><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"><inist: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></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation><affiliation wicri:level="1"><inist: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></inist:fA14><country>Japon</country><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"><inist: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></inist:fA14><country>Japon</country><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"><inist: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></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Microbes and infection</title><title level="j" type="abbreviated">Microbes infect.</title><idno type="ISSN">1286-4579</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Microbes and infection</title><title level="j" type="abbreviated">Microbes infect.</title><idno type="ISSN">1286-4579</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Substitution (genetics)</term><term>Amino Acid Substitution (immunology)</term><term>Animals</term><term>Antibodies, Monoclonal (immunology)</term><term>Antibodies, Viral (immunology)</term><term>Immunotherapy</term><term>Membrane Glycoproteins (genetics)</term><term>Membrane Glycoproteins (immunology)</term><term>Mice</term><term>Mutation</term><term>Mutation, Missense</term><term>Neutralization</term><term>Neutralization Tests</term><term>Neutralizing antibody</term><term>Phenotype</term><term>Protein</term><term>Protein Structure, Tertiary</term><term>SARS Virus (genetics)</term><term>SARS Virus (growth & development)</term><term>SARS Virus (immunology)</term><term>Severe acute respiratory syndrome virus</term><term>Spike Glycoprotein, Coronavirus</term><term>Viral Envelope Proteins (genetics)</term><term>Viral Envelope Proteins (immunology)</term><term>Viral Plaque Assay</term><term>Virus Replication (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps antiviraux (immunologie)</term><term>Anticorps monoclonaux (immunologie)</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires (génétique)</term><term>Glycoprotéines membranaires (immunologie)</term><term>Mutation faux-sens</term><term>Méthode des plages virales</term><term>Protéines de l'enveloppe virale (génétique)</term><term>Protéines de l'enveloppe virale (immunologie)</term><term>Réplication virale (immunologie)</term><term>Souris</term><term>Structure tertiaire des protéines</term><term>Substitution d'acide aminé (génétique)</term><term>Substitution d'acide aminé (immunologie)</term><term>Tests de neutralisation</term><term>Virus du SRAS (croissance et développement)</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Antibodies, Viral</term><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Amino Acid Substitution</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term><term>Substitution d'acide aminé</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps monoclonaux</term><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term><term>Réplication virale</term><term>Substitution d'acide aminé</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Amino Acid Substitution</term><term>SARS Virus</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Mice</term><term>Mutation, Missense</term><term>Neutralization Tests</term><term>Protein Structure, Tertiary</term><term>Spike Glycoprotein, Coronavirus</term><term>Viral Plaque Assay</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Animaux</term><term>Glycoprotéine de spicule des coronavirus</term><term>Mutation faux-sens</term><term>Méthode des plages virales</term><term>Souris</term><term>Structure tertiaire des protéines</term><term>Tests de neutralisation</term><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></keywords></textClass></profileDesc></teiHeader><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><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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