Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses.
Identifieur interne : 004839 ( Main/Exploration ); précédent : 004838; suivant : 004840Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses.
Auteurs : Zhi-Yong Yang [États-Unis] ; Heidi C. Werner ; Wing-Pui Kong ; Kwanyee Leung ; Elisabetta Traggiai ; Antonio Lanzavecchia ; Gary J. NabelSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2005.
Descripteurs français
- KwdFr :
- Anticorps antiviraux (immunologie), Anticorps antiviraux (pharmacologie), Carboxypeptidases (immunologie), Flambées de maladies, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (génétique), Glycoprotéines membranaires (immunologie), Humains, Lignée cellulaire tumorale, Mutation faux-sens, Peptidyl-Dipeptidase A, Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (immunologie), Récepteurs viraux, Variation des antigènes (génétique), Variation génétique (immunologie), Virus du SRAS (génétique), Virus du SRAS (immunologie), Épitopes.
- MESH :
- génétique : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Variation des antigènes, Virus du SRAS.
- immunologie : Anticorps antiviraux, Carboxypeptidases, Glycoprotéines membranaires, Protéines de l'enveloppe virale, Variation génétique, Virus du SRAS.
- pharmacologie : Anticorps antiviraux.
- Flambées de maladies, Glycoprotéine de spicule des coronavirus, Humains, Lignée cellulaire tumorale, Mutation faux-sens, Peptidyl-Dipeptidase A, Récepteurs viraux, Épitopes.
English descriptors
- KwdEn :
- Antibodies, Viral (immunology), Antibodies, Viral (pharmacology), Antigenic Variation (genetics), Carboxypeptidases (immunology), Cell Line, Tumor, Disease Outbreaks, Epitopes, Genetic Variation (immunology), Humans, Membrane Glycoproteins (genetics), Membrane Glycoproteins (immunology), Mutation, Missense, Peptidyl-Dipeptidase A, Receptors, Virus, SARS Virus (genetics), SARS Virus (immunology), Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (genetics), Viral Envelope Proteins (immunology).
- MESH :
- chemical , genetics : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , immunology : Antibodies, Viral, Carboxypeptidases, Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , pharmacology : Antibodies, Viral.
- genetics : Antigenic Variation, SARS Virus.
- immunology : Genetic Variation, SARS Virus.
- Cell Line, Tumor, Disease Outbreaks, Epitopes, Humans, Mutation, Missense, Peptidyl-Dipeptidase A, Receptors, Virus, Spike Glycoprotein, Coronavirus.
Abstract
Molecular characterization of the severe acute respiratory syndrome coronavirus has revealed genetic diversity among isolates. The spike (S) glycoprotein, the major target for vaccine and immune therapy, shows up to 17 substitutions in its 1,255-aa sequence; however, the biologic significance of these changes is unknown. Here, the functional effects of S mutations have been determined by analyzing their affinity for a viral receptor, human angiotensin-converting enzyme 2 (hACE-2), and their sensitivity to Ab neutralization with viral pseudotypes. Although minor differences among eight strains transmitted during human outbreaks in early 2003 were found, substantial functional changes were detected in S derived from a case in late 2003 from Guangdong province [S(GD03T0013)] and from two palm civets, S(SZ3) and S(SZ16). S(GD03T0013) depended less on the hACE-2 receptor and was markedly resistant to Ab inhibition. Unexpectedly, Abs that neutralized most human S glycoproteins enhanced entry mediated by the civet virus S glycoproteins. The mechanism of enhancement involved the interaction of Abs with conformational epitopes in the hACE-2-binding domain. Finally, improved immunogens and mAbs that minimize this complication have been defined. These data show that the entry of severe acute respiratory syndrome coronaviruses can be enhanced by Abs, and they underscore the need to address the evolving diversity of this newly emerged virus for vaccines and immune therapies.
DOI: 10.1073/pnas.0409065102
PubMed: 15642942
Affiliations:
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Werner</name></author><author><name sortKey="Kong, Wing Pui" sort="Kong, Wing Pui" uniqKey="Kong W" first="Wing-Pui" last="Kong">Wing-Pui Kong</name></author><author><name sortKey="Leung, Kwanyee" sort="Leung, Kwanyee" uniqKey="Leung K" first="Kwanyee" last="Leung">Kwanyee Leung</name></author><author><name sortKey="Traggiai, Elisabetta" sort="Traggiai, Elisabetta" uniqKey="Traggiai E" first="Elisabetta" last="Traggiai">Elisabetta Traggiai</name></author><author><name sortKey="Lanzavecchia, Antonio" sort="Lanzavecchia, Antonio" uniqKey="Lanzavecchia A" first="Antonio" last="Lanzavecchia">Antonio Lanzavecchia</name></author><author><name sortKey="Nabel, Gary J" sort="Nabel, Gary J" uniqKey="Nabel G" first="Gary J" last="Nabel">Gary J. Nabel</name></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><imprint><date when="2005" type="published">2005</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antibodies, Viral (immunology)</term><term>Antibodies, Viral (pharmacology)</term><term>Antigenic Variation (genetics)</term><term>Carboxypeptidases (immunology)</term><term>Cell Line, Tumor</term><term>Disease Outbreaks</term><term>Epitopes</term><term>Genetic Variation (immunology)</term><term>Humans</term><term>Membrane Glycoproteins (genetics)</term><term>Membrane Glycoproteins (immunology)</term><term>Mutation, Missense</term><term>Peptidyl-Dipeptidase A</term><term>Receptors, Virus</term><term>SARS Virus (genetics)</term><term>SARS Virus (immunology)</term><term>Spike Glycoprotein, Coronavirus</term><term>Viral Envelope Proteins (genetics)</term><term>Viral Envelope Proteins (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Anticorps antiviraux (immunologie)</term><term>Anticorps antiviraux (pharmacologie)</term><term>Carboxypeptidases (immunologie)</term><term>Flambées de maladies</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires (génétique)</term><term>Glycoprotéines membranaires (immunologie)</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Mutation faux-sens</term><term>Peptidyl-Dipeptidase A</term><term>Protéines de l'enveloppe virale (génétique)</term><term>Protéines de l'enveloppe virale (immunologie)</term><term>Récepteurs viraux</term><term>Variation des antigènes (génétique)</term><term>Variation génétique (immunologie)</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (immunologie)</term><term>Épitopes</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, Viral</term><term>Carboxypeptidases</term><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Antigenic Variation</term><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>Variation des antigènes</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Carboxypeptidases</term><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term><term>Variation génétique</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Genetic Variation</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Anticorps antiviraux</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line, Tumor</term><term>Disease Outbreaks</term><term>Epitopes</term><term>Humans</term><term>Mutation, Missense</term><term>Peptidyl-Dipeptidase A</term><term>Receptors, Virus</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Flambées de maladies</term><term>Glycoprotéine de spicule des coronavirus</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Mutation faux-sens</term><term>Peptidyl-Dipeptidase A</term><term>Récepteurs viraux</term><term>Épitopes</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Molecular characterization of the severe acute respiratory syndrome coronavirus has revealed genetic diversity among isolates. The spike (S) glycoprotein, the major target for vaccine and immune therapy, shows up to 17 substitutions in its 1,255-aa sequence; however, the biologic significance of these changes is unknown. Here, the functional effects of S mutations have been determined by analyzing their affinity for a viral receptor, human angiotensin-converting enzyme 2 (hACE-2), and their sensitivity to Ab neutralization with viral pseudotypes. Although minor differences among eight strains transmitted during human outbreaks in early 2003 were found, substantial functional changes were detected in S derived from a case in late 2003 from Guangdong province [S(GD03T0013)] and from two palm civets, S(SZ3) and S(SZ16). S(GD03T0013) depended less on the hACE-2 receptor and was markedly resistant to Ab inhibition. Unexpectedly, Abs that neutralized most human S glycoproteins enhanced entry mediated by the civet virus S glycoproteins. The mechanism of enhancement involved the interaction of Abs with conformational epitopes in the hACE-2-binding domain. Finally, improved immunogens and mAbs that minimize this complication have been defined. These data show that the entry of severe acute respiratory syndrome coronaviruses can be enhanced by Abs, and they underscore the need to address the evolving diversity of this newly emerged virus for vaccines and immune therapies.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><noCountry><name sortKey="Kong, Wing Pui" sort="Kong, Wing Pui" uniqKey="Kong W" first="Wing-Pui" last="Kong">Wing-Pui Kong</name><name sortKey="Lanzavecchia, Antonio" sort="Lanzavecchia, Antonio" uniqKey="Lanzavecchia A" first="Antonio" last="Lanzavecchia">Antonio Lanzavecchia</name><name sortKey="Leung, Kwanyee" sort="Leung, Kwanyee" uniqKey="Leung K" first="Kwanyee" last="Leung">Kwanyee Leung</name><name sortKey="Nabel, Gary J" sort="Nabel, Gary J" uniqKey="Nabel G" first="Gary J" last="Nabel">Gary J. Nabel</name><name sortKey="Traggiai, Elisabetta" sort="Traggiai, Elisabetta" uniqKey="Traggiai E" first="Elisabetta" last="Traggiai">Elisabetta Traggiai</name><name sortKey="Werner, Heidi C" sort="Werner, Heidi C" uniqKey="Werner H" first="Heidi C" last="Werner">Heidi C. Werner</name></noCountry><country name="États-Unis"><region name="Maryland"><name sortKey="Yang, Zhi Yong" sort="Yang, Zhi Yong" uniqKey="Yang Z" first="Zhi-Yong" last="Yang">Zhi-Yong Yang</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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