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Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion

Identifieur interne : 000335 ( Main/Exploration ); précédent : 000334; suivant : 000336

Unexpected 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 :

RBID : PMC:6751136

Descripteurs français

English descriptors

Abstract

Summary

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


Affiliations:


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<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>
</textClass>
</profileDesc>
</teiHeader>
<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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</listBibl>
</div1>
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</TEI>
<affiliations>
<list>
<country>
<li>France</li>
<li>Royaume-Uni</li>
<li>Suisse</li>
<li>États-Unis</li>
</country>
<region>
<li>Washington (État)</li>
<li>Île-de-France</li>
</region>
<settlement>
<li>Paris</li>
<li>Seattle</li>
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<orgName>
<li>Université de Washington</li>
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<region name="Washington (État)">
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<country name="France">
<region name="Île-de-France">
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<country name="Suisse">
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<name sortKey="Lanzavecchia, Antonio" sort="Lanzavecchia, Antonio" uniqKey="Lanzavecchia A" first="Antonio" last="Lanzavecchia">Antonio Lanzavecchia</name>
</country>
<country name="Royaume-Uni">
<noRegion>
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<name sortKey="Dai, Mian" sort="Dai, Mian" uniqKey="Dai M" first="Mian" last="Dai">Mian Dai</name>
<name sortKey="Zambon, Maria" sort="Zambon, Maria" uniqKey="Zambon M" first="Maria" last="Zambon">Maria Zambon</name>
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</affiliations>
</record>

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