Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion
Identifieur interne : 002099 ( Ncbi/Curation ); précédent : 002098; suivant : 002100Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion
Auteurs : Alexandra C. Walls [États-Unis] ; Xiaoli Xiong [États-Unis] ; Young-Jun Park [États-Unis] ; M. Alejandra Tortorici [États-Unis, France] ; Joost Snijder [États-Unis] ; Joel Quispe [États-Unis] ; Elisabetta Cameroni [Suisse] ; Robin Gopal [Royaume-Uni] ; Mian Dai [Royaume-Uni] ; Antonio Lanzavecchia [Suisse] ; Maria Zambon [Royaume-Uni] ; Félix A. Rey [France] ; Davide Corti [Suisse] ; David Veesler [États-Unis]Source :
- Cell [ 0092-8674 ] ; 2019.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (immunologie), Anticorps monoclonaux (immunologie), Anticorps neutralisants (immunologie), Cellules HEK293, Cellules Vero, Coronavirus (immunologie), Coronavirus (métabolisme), Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Coronavirus du syndrome respiratoire du Moyen-Orient (métabolisme), Glycoprotéine de spicule des coronavirus (métabolisme), Glycoprotéine de spicule des coronavirus (physiologie), Glycoprotéine de spicule des coronavirus (ultrastructure), Humains, Immunité humorale (immunologie), Infections à coronavirus (immunologie), Liaison aux protéines, Mimétisme moléculaire (immunologie), Pénétration virale, Récepteurs viraux (métabolisme), Virus du SRAS (immunologie), Virus du SRAS (métabolisme).
- MESH :
- immunologie : Anticorps antiviraux, Anticorps monoclonaux, Anticorps neutralisants, Coronavirus, Coronavirus du syndrome respiratoire du Moyen-Orient, Immunité humorale, Infections à coronavirus, Mimétisme moléculaire, Virus du SRAS.
- métabolisme : Coronavirus, Coronavirus du syndrome respiratoire du Moyen-Orient, Glycoprotéine de spicule des coronavirus, Récepteurs viraux, Virus du SRAS.
- physiologie : Glycoprotéine de spicule des coronavirus.
- ultrastructure : Animaux, Cellules HEK293, Cellules Vero, Glycoprotéine de spicule des coronavirus, Humains, Liaison aux protéines, Pénétration virale.
English descriptors
- KwdEn :
- Animals, Antibodies, Monoclonal (immunology), Antibodies, Neutralizing (immunology), Antibodies, Viral (immunology), Chlorocebus aethiops, Coronavirus (immunology), Coronavirus (metabolism), Coronavirus Infections (immunology), HEK293 Cells, Humans, Immunity, Humoral (immunology), Middle East Respiratory Syndrome Coronavirus (immunology), Middle East Respiratory Syndrome Coronavirus (metabolism), Molecular Mimicry (immunology), Protein Binding, Receptors, Virus (metabolism), SARS Virus (immunology), SARS Virus (metabolism), Spike Glycoprotein, Coronavirus (metabolism), Spike Glycoprotein, Coronavirus (physiology), Spike Glycoprotein, Coronavirus (ultrastructure), Vero Cells, Virus Internalization.
- MESH :
- chemical , immunology : Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral.
- immunology : Coronavirus, Coronavirus Infections, Immunity, Humoral, Middle East Respiratory Syndrome Coronavirus, Molecular Mimicry, SARS Virus.
- metabolism : Coronavirus, Middle East Respiratory Syndrome Coronavirus, Receptors, Virus, SARS Virus, Spike Glycoprotein, Coronavirus.
- chemical , physiology : Spike Glycoprotein, Coronavirus.
- chemical , ultrastructure : Spike Glycoprotein, Coronavirus.
- Animals, Chlorocebus aethiops, HEK293 Cells, Humans, Protein Binding, Vero Cells, Virus Internalization.
Abstract
Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses. The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies. To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors. Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry. These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism.
Url:
DOI: 10.1016/j.cell.2018.12.028
PubMed: 30712865
PubMed Central: 6751136
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PMC:6751136Le document en format XML
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<author><name sortKey="Tortorici, M Alejandra" sort="Tortorici, M Alejandra" uniqKey="Tortorici M" first="M. Alejandra" last="Tortorici">M. Alejandra Tortorici</name>
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<author><name sortKey="Quispe, Joel" sort="Quispe, Joel" uniqKey="Quispe J" first="Joel" last="Quispe">Joel Quispe</name>
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<author><name sortKey="Cameroni, Elisabetta" sort="Cameroni, Elisabetta" uniqKey="Cameroni E" first="Elisabetta" last="Cameroni">Elisabetta Cameroni</name>
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<author><name sortKey="Dai, Mian" sort="Dai, Mian" uniqKey="Dai M" first="Mian" last="Dai">Mian Dai</name>
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<author><name sortKey="Lanzavecchia, Antonio" sort="Lanzavecchia, Antonio" uniqKey="Lanzavecchia A" first="Antonio" last="Lanzavecchia">Antonio Lanzavecchia</name>
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<author><name sortKey="Zambon, Maria" sort="Zambon, Maria" uniqKey="Zambon M" first="Maria" last="Zambon">Maria Zambon</name>
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<author><name sortKey="Veesler, David" sort="Veesler, David" uniqKey="Veesler D" first="David" last="Veesler">David Veesler</name>
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</affiliation>
</author>
</analytic>
<series><title level="j">Cell</title>
<idno type="ISSN">0092-8674</idno>
<idno type="eISSN">1097-4172</idno>
<imprint><date when="2019">2019</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Antibodies, Monoclonal (immunology)</term>
<term>Antibodies, Neutralizing (immunology)</term>
<term>Antibodies, Viral (immunology)</term>
<term>Chlorocebus aethiops</term>
<term>Coronavirus (immunology)</term>
<term>Coronavirus (metabolism)</term>
<term>Coronavirus Infections (immunology)</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Immunity, Humoral (immunology)</term>
<term>Middle East Respiratory Syndrome Coronavirus (immunology)</term>
<term>Middle East Respiratory Syndrome Coronavirus (metabolism)</term>
<term>Molecular Mimicry (immunology)</term>
<term>Protein Binding</term>
<term>Receptors, Virus (metabolism)</term>
<term>SARS Virus (immunology)</term>
<term>SARS Virus (metabolism)</term>
<term>Spike Glycoprotein, Coronavirus (metabolism)</term>
<term>Spike Glycoprotein, Coronavirus (physiology)</term>
<term>Spike Glycoprotein, Coronavirus (ultrastructure)</term>
<term>Vero Cells</term>
<term>Virus Internalization</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Anticorps antiviraux (immunologie)</term>
<term>Anticorps monoclonaux (immunologie)</term>
<term>Anticorps neutralisants (immunologie)</term>
<term>Cellules HEK293</term>
<term>Cellules Vero</term>
<term>Coronavirus (immunologie)</term>
<term>Coronavirus (métabolisme)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (métabolisme)</term>
<term>Glycoprotéine de spicule des coronavirus (métabolisme)</term>
<term>Glycoprotéine de spicule des coronavirus (physiologie)</term>
<term>Glycoprotéine de spicule des coronavirus (ultrastructure)</term>
<term>Humains</term>
<term>Immunité humorale (immunologie)</term>
<term>Infections à coronavirus (immunologie)</term>
<term>Liaison aux protéines</term>
<term>Mimétisme moléculaire (immunologie)</term>
<term>Pénétration virale</term>
<term>Récepteurs viraux (métabolisme)</term>
<term>Virus du SRAS (immunologie)</term>
<term>Virus du SRAS (métabolisme)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Monoclonal</term>
<term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term>
<term>Anticorps monoclonaux</term>
<term>Anticorps neutralisants</term>
<term>Coronavirus</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Immunité humorale</term>
<term>Infections à coronavirus</term>
<term>Mimétisme moléculaire</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus</term>
<term>Coronavirus Infections</term>
<term>Immunity, Humoral</term>
<term>Middle East Respiratory Syndrome Coronavirus</term>
<term>Molecular Mimicry</term>
<term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Coronavirus</term>
<term>Middle East Respiratory Syndrome Coronavirus</term>
<term>Receptors, Virus</term>
<term>SARS Virus</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Coronavirus</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Récepteurs viraux</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Glycoprotéine de spicule des coronavirus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="ultrastructure" xml:lang="en"><term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Chlorocebus aethiops</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Protein Binding</term>
<term>Vero Cells</term>
<term>Virus Internalization</term>
</keywords>
<keywords scheme="MESH" qualifier="ultrastructure" xml:lang="fr"><term>Animaux</term>
<term>Cellules HEK293</term>
<term>Cellules Vero</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Pénétration virale</term>
</keywords>
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<front><div type="abstract" xml:lang="en"><title>Summary</title>
<p>Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses. The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies. To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors. Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry. These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism.</p>
</div>
</front>
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