MersV1, Main, Exploration, bibRecord, 000141

Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry.

Identifieur interne : 000141 ( Main/Exploration ); précédent : 000140; suivant : 000142

Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry.

Auteurs : Yushun Wan [États-Unis] ; Jian Shang [États-Unis] ; Shihui Sun [République populaire de Chine] ; Wanbo Tai [États-Unis] ; Jing Chen [République populaire de Chine] ; Qibin Geng [États-Unis] ; Lei He [République populaire de Chine] ; Yuehong Chen [République populaire de Chine] ; Jianming Wu [États-Unis] ; Zhengli Shi [République populaire de Chine] ; Yusen Zhou [République populaire de Chine] ; Lanying Du [États-Unis] ; Fang Li [États-Unis]

Source :

Journal of virology [ 1098-5514 ] ; 2020.

RBID : pubmed:31826992

Descripteurs français

English descriptors

KwdEn :
- Antibodies, Monoclonal (immunology), Antibodies, Monoclonal (metabolism), Antibodies, Neutralizing (immunology), Antibodies, Neutralizing (metabolism), Antibodies, Viral (immunology), Antibodies, Viral (metabolism), Antibody-Dependent Enhancement, Cell Line, Dipeptidyl Peptidase 4 (metabolism), Humans, Immunoglobulin Fab Fragments (immunology), Immunoglobulin Fab Fragments (metabolism), Middle East Respiratory Syndrome Coronavirus (immunology), Middle East Respiratory Syndrome Coronavirus (pathogenicity), Middle East Respiratory Syndrome Coronavirus (physiology), Peptide Hydrolases (metabolism), Proprotein Convertases (antagonists & inhibitors), Proprotein Convertases (metabolism), Protein Conformation, Protein Domains, Protein Multimerization, Receptors, Fc (metabolism), Receptors, IgG (immunology), Receptors, IgG (metabolism), Receptors, Virus (metabolism), Spike Glycoprotein, Coronavirus (chemistry), Spike Glycoprotein, Coronavirus (immunology), Spike Glycoprotein, Coronavirus (metabolism), Trypsin (metabolism), Virus Internalization.
MESH :
- chemical , antagonists & inhibitors : Proprotein Convertases.
- chemical , chemistry : Spike Glycoprotein, Coronavirus.
- chemical , immunology : Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Immunoglobulin Fab Fragments, Receptors, IgG, Spike Glycoprotein, Coronavirus.
- chemical , metabolism : Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Dipeptidyl Peptidase 4, Immunoglobulin Fab Fragments, Peptide Hydrolases, Proprotein Convertases, Receptors, Fc, Receptors, IgG, Receptors, Virus, Spike Glycoprotein, Coronavirus, Trypsin.
- immunology : Middle East Respiratory Syndrome Coronavirus.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- physiology : Middle East Respiratory Syndrome Coronavirus.
- Antibody-Dependent Enhancement, Cell Line, Humans, Protein Conformation, Protein Domains, Protein Multimerization, Virus Internalization.

Abstract

Antibody-dependent enhancement (ADE) of viral entry has been a major concern for epidemiology, vaccine development, and antibody-based drug therapy. However, the molecular mechanism behind ADE is still elusive. Coronavirus spike protein mediates viral entry into cells by first binding to a receptor on the host cell surface and then fusing viral and host membranes. In this study, we investigated how a neutralizing monoclonal antibody (MAb), which targets the receptor-binding domain (RBD) of Middle East respiratory syndrome (MERS) coronavirus spike, mediates viral entry using pseudovirus entry and biochemical assays. Our results showed that MAb binds to the virus surface spike, allowing it to undergo conformational changes and become prone to proteolytic activation. Meanwhile, MAb binds to cell surface IgG Fc receptor, guiding viral entry through canonical viral-receptor-dependent pathways. Our data suggest that the antibody/Fc-receptor complex functionally mimics viral receptor in mediating viral entry. Moreover, we characterized MAb dosages in viral-receptor-dependent, Fc-receptor-dependent, and both-receptors-dependent viral entry pathways, delineating guidelines on MAb usages in treating viral infections. Our study reveals a novel molecular mechanism for antibody-enhanced viral entry and can guide future vaccination and antiviral strategies.IMPORTANCE Antibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into IgG Fc receptor-expressing cells through canonical viral-receptor-dependent pathways. We further evaluated how antibody dosages impacted viral entry into cells expressing viral receptor, Fc receptor, or both receptors. This study reveals complex roles of antibodies in viral entry and can guide future vaccine design and antibody-based drug therapy.

DOI: 10.1128/JVI.02015-19
PubMed: 31826992

Affiliations:

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry.</title>
<author><name sortKey="Wan, Yushun" sort="Wan, Yushun" uniqKey="Wan Y" first="Yushun" last="Wan">Yushun Wan</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota</wicri:regionArea>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shang, Jian" sort="Shang, Jian" uniqKey="Shang J" first="Jian" last="Shang">Jian Shang</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota</wicri:regionArea>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sun, Shihui" sort="Sun, Shihui" uniqKey="Sun S" first="Shihui" last="Sun">Shihui Sun</name>
<affiliation wicri:level="3"><nlm:affiliation>Laboratory of Infection and Immunity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Laboratory of Infection and Immunity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tai, Wanbo" sort="Tai, Wanbo" uniqKey="Tai W" first="Wanbo" last="Tai">Wanbo Tai</name>
<affiliation wicri:level="2"><nlm:affiliation>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chen, Jing" sort="Chen, Jing" uniqKey="Chen J" first="Jing" last="Chen">Jing Chen</name>
<affiliation wicri:level="1"><nlm:affiliation>Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei Province, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei Province</wicri:regionArea>
<wicri:noRegion>Hubei Province</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Geng, Qibin" sort="Geng, Qibin" uniqKey="Geng Q" first="Qibin" last="Geng">Qibin Geng</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota</wicri:regionArea>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="He, Lei" sort="He, Lei" uniqKey="He L" first="Lei" last="He">Lei He</name>
<affiliation wicri:level="3"><nlm:affiliation>Laboratory of Infection and Immunity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Laboratory of Infection and Immunity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chen, Yuehong" sort="Chen, Yuehong" uniqKey="Chen Y" first="Yuehong" last="Chen">Yuehong Chen</name>
<affiliation wicri:level="3"><nlm:affiliation>Laboratory of Infection and Immunity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Laboratory of Infection and Immunity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wu, Jianming" sort="Wu, Jianming" uniqKey="Wu J" first="Jianming" last="Wu">Jianming Wu</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota</wicri:regionArea>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shi, Zhengli" sort="Shi, Zhengli" uniqKey="Shi Z" first="Zhengli" last="Shi">Zhengli Shi</name>
<affiliation wicri:level="1"><nlm:affiliation>Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei Province, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei Province</wicri:regionArea>
<wicri:noRegion>Hubei Province</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name>
<affiliation wicri:level="3"><nlm:affiliation>Laboratory of Infection and Immunity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Laboratory of Infection and Immunity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name>
<affiliation wicri:level="1"><nlm:affiliation>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA LDu@nybc.org lifang@umn.edu.</nlm:affiliation>
<country wicri:rule="url">États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA LDu@nybc.org lifang@umn.edu.</nlm:affiliation>
<country wicri:rule="url">États-Unis</country>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2020">2020</date>
<idno type="RBID">pubmed:31826992</idno>
<idno type="pmid">31826992</idno>
<idno type="doi">10.1128/JVI.02015-19</idno>
<idno type="wicri:Area/PubMed/Corpus">000335</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000335</idno>
<idno type="wicri:Area/PubMed/Curation">000335</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000335</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000139</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000139</idno>
<idno type="wicri:Area/Ncbi/Merge">002429</idno>
<idno type="wicri:Area/Ncbi/Curation">002429</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">002429</idno>
<idno type="wicri:Area/Main/Merge">000144</idno>
<idno type="wicri:Area/Main/Curation">000141</idno>
<idno type="wicri:Area/Main/Exploration">000141</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry.</title>
<author><name sortKey="Wan, Yushun" sort="Wan, Yushun" uniqKey="Wan Y" first="Yushun" last="Wan">Yushun Wan</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota</wicri:regionArea>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shang, Jian" sort="Shang, Jian" uniqKey="Shang J" first="Jian" last="Shang">Jian Shang</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota</wicri:regionArea>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sun, Shihui" sort="Sun, Shihui" uniqKey="Sun S" first="Shihui" last="Sun">Shihui Sun</name>
<affiliation wicri:level="3"><nlm:affiliation>Laboratory of Infection and Immunity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Laboratory of Infection and Immunity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tai, Wanbo" sort="Tai, Wanbo" uniqKey="Tai W" first="Wanbo" last="Tai">Wanbo Tai</name>
<affiliation wicri:level="2"><nlm:affiliation>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chen, Jing" sort="Chen, Jing" uniqKey="Chen J" first="Jing" last="Chen">Jing Chen</name>
<affiliation wicri:level="1"><nlm:affiliation>Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei Province, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei Province</wicri:regionArea>
<wicri:noRegion>Hubei Province</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Geng, Qibin" sort="Geng, Qibin" uniqKey="Geng Q" first="Qibin" last="Geng">Qibin Geng</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota</wicri:regionArea>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="He, Lei" sort="He, Lei" uniqKey="He L" first="Lei" last="He">Lei He</name>
<affiliation wicri:level="3"><nlm:affiliation>Laboratory of Infection and Immunity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Laboratory of Infection and Immunity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chen, Yuehong" sort="Chen, Yuehong" uniqKey="Chen Y" first="Yuehong" last="Chen">Yuehong Chen</name>
<affiliation wicri:level="3"><nlm:affiliation>Laboratory of Infection and Immunity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Laboratory of Infection and Immunity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wu, Jianming" sort="Wu, Jianming" uniqKey="Wu J" first="Jianming" last="Wu">Jianming Wu</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota</wicri:regionArea>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shi, Zhengli" sort="Shi, Zhengli" uniqKey="Shi Z" first="Zhengli" last="Shi">Zhengli Shi</name>
<affiliation wicri:level="1"><nlm:affiliation>Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei Province, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei Province</wicri:regionArea>
<wicri:noRegion>Hubei Province</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name>
<affiliation wicri:level="3"><nlm:affiliation>Laboratory of Infection and Immunity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Laboratory of Infection and Immunity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name>
<affiliation wicri:level="1"><nlm:affiliation>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA LDu@nybc.org lifang@umn.edu.</nlm:affiliation>
<country wicri:rule="url">États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA LDu@nybc.org lifang@umn.edu.</nlm:affiliation>
<country wicri:rule="url">États-Unis</country>
</affiliation>
</author>
</analytic>
<series><title level="j">Journal of virology</title>
<idno type="eISSN">1098-5514</idno>
<imprint><date when="2020" type="published">2020</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antibodies, Monoclonal (immunology)</term>
<term>Antibodies, Monoclonal (metabolism)</term>
<term>Antibodies, Neutralizing (immunology)</term>
<term>Antibodies, Neutralizing (metabolism)</term>
<term>Antibodies, Viral (immunology)</term>
<term>Antibodies, Viral (metabolism)</term>
<term>Antibody-Dependent Enhancement</term>
<term>Cell Line</term>
<term>Dipeptidyl Peptidase 4 (metabolism)</term>
<term>Humans</term>
<term>Immunoglobulin Fab Fragments (immunology)</term>
<term>Immunoglobulin Fab Fragments (metabolism)</term>
<term>Middle East Respiratory Syndrome Coronavirus (immunology)</term>
<term>Middle East Respiratory Syndrome Coronavirus (pathogenicity)</term>
<term>Middle East Respiratory Syndrome Coronavirus (physiology)</term>
<term>Peptide Hydrolases (metabolism)</term>
<term>Proprotein Convertases (antagonists & inhibitors)</term>
<term>Proprotein Convertases (metabolism)</term>
<term>Protein Conformation</term>
<term>Protein Domains</term>
<term>Protein Multimerization</term>
<term>Receptors, Fc (metabolism)</term>
<term>Receptors, IgG (immunology)</term>
<term>Receptors, IgG (metabolism)</term>
<term>Receptors, Virus (metabolism)</term>
<term>Spike Glycoprotein, Coronavirus (chemistry)</term>
<term>Spike Glycoprotein, Coronavirus (immunology)</term>
<term>Spike Glycoprotein, Coronavirus (metabolism)</term>
<term>Trypsin (metabolism)</term>
<term>Virus Internalization</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Anticorps antiviraux (immunologie)</term>
<term>Anticorps antiviraux (métabolisme)</term>
<term>Anticorps monoclonaux (immunologie)</term>
<term>Anticorps monoclonaux (métabolisme)</term>
<term>Anticorps neutralisants (immunologie)</term>
<term>Anticorps neutralisants (métabolisme)</term>
<term>Conformation des protéines</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie)</term>
<term>Dipeptidyl peptidase 4 (métabolisme)</term>
<term>Domaines protéiques</term>
<term>Facilitation dépendante des anticorps</term>
<term>Fragments Fab d'immunoglobuline (immunologie)</term>
<term>Fragments Fab d'immunoglobuline (métabolisme)</term>
<term>Glycoprotéine de spicule des coronavirus ()</term>
<term>Glycoprotéine de spicule des coronavirus (immunologie)</term>
<term>Glycoprotéine de spicule des coronavirus (métabolisme)</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Multimérisation de protéines</term>
<term>Peptide hydrolases (métabolisme)</term>
<term>Proprotein convertases (antagonistes et inhibiteurs)</term>
<term>Proprotein convertases (métabolisme)</term>
<term>Pénétration virale</term>
<term>Récepteur Fc (métabolisme)</term>
<term>Récepteurs du fragment Fc des IgG (immunologie)</term>
<term>Récepteurs du fragment Fc des IgG (métabolisme)</term>
<term>Récepteurs viraux (métabolisme)</term>
<term>Trypsine (métabolisme)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Proprotein Convertases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Monoclonal</term>
<term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral</term>
<term>Immunoglobulin Fab Fragments</term>
<term>Receptors, IgG</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antibodies, Monoclonal</term>
<term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral</term>
<term>Dipeptidyl Peptidase 4</term>
<term>Immunoglobulin Fab Fragments</term>
<term>Peptide Hydrolases</term>
<term>Proprotein Convertases</term>
<term>Receptors, Fc</term>
<term>Receptors, IgG</term>
<term>Receptors, Virus</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Trypsin</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Proprotein convertases</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term>
<term>Anticorps monoclonaux</term>
<term>Anticorps neutralisants</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Fragments Fab d'immunoglobuline</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Récepteurs du fragment Fc des IgG</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Anticorps antiviraux</term>
<term>Anticorps monoclonaux</term>
<term>Anticorps neutralisants</term>
<term>Dipeptidyl peptidase 4</term>
<term>Fragments Fab d'immunoglobuline</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Peptide hydrolases</term>
<term>Proprotein convertases</term>
<term>Récepteur Fc</term>
<term>Récepteurs du fragment Fc des IgG</term>
<term>Récepteurs viraux</term>
<term>Trypsine</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Antibody-Dependent Enhancement</term>
<term>Cell Line</term>
<term>Humans</term>
<term>Protein Conformation</term>
<term>Protein Domains</term>
<term>Protein Multimerization</term>
<term>Virus Internalization</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Conformation des protéines</term>
<term>Domaines protéiques</term>
<term>Facilitation dépendante des anticorps</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Multimérisation de protéines</term>
<term>Pénétration virale</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Antibody-dependent enhancement (ADE) of viral entry has been a major concern for epidemiology, vaccine development, and antibody-based drug therapy. However, the molecular mechanism behind ADE is still elusive. Coronavirus spike protein mediates viral entry into cells by first binding to a receptor on the host cell surface and then fusing viral and host membranes. In this study, we investigated how a neutralizing monoclonal antibody (MAb), which targets the receptor-binding domain (RBD) of Middle East respiratory syndrome (MERS) coronavirus spike, mediates viral entry using pseudovirus entry and biochemical assays. Our results showed that MAb binds to the virus surface spike, allowing it to undergo conformational changes and become prone to proteolytic activation. Meanwhile, MAb binds to cell surface IgG Fc receptor, guiding viral entry through canonical viral-receptor-dependent pathways. Our data suggest that the antibody/Fc-receptor complex functionally mimics viral receptor in mediating viral entry. Moreover, we characterized MAb dosages in viral-receptor-dependent, Fc-receptor-dependent, and both-receptors-dependent viral entry pathways, delineating guidelines on MAb usages in treating viral infections. Our study reveals a novel molecular mechanism for antibody-enhanced viral entry and can guide future vaccination and antiviral strategies.<b>IMPORTANCE</b>
 Antibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into IgG Fc receptor-expressing cells through canonical viral-receptor-dependent pathways. We further evaluated how antibody dosages impacted viral entry into cells expressing viral receptor, Fc receptor, or both receptors. This study reveals complex roles of antibodies in viral entry and can guide future vaccine design and antibody-based drug therapy.</div>
</front>
</TEI>
<affiliations><list><country><li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Minnesota</li>
<li>État de New York</li>
</region>
<settlement><li>Pékin</li>
</settlement>
</list>
<tree><country name="États-Unis"><region name="Minnesota"><name sortKey="Wan, Yushun" sort="Wan, Yushun" uniqKey="Wan Y" first="Yushun" last="Wan">Yushun Wan</name>
</region>
<name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name>
<name sortKey="Geng, Qibin" sort="Geng, Qibin" uniqKey="Geng Q" first="Qibin" last="Geng">Qibin Geng</name>
<name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name>
<name sortKey="Shang, Jian" sort="Shang, Jian" uniqKey="Shang J" first="Jian" last="Shang">Jian Shang</name>
<name sortKey="Tai, Wanbo" sort="Tai, Wanbo" uniqKey="Tai W" first="Wanbo" last="Tai">Wanbo Tai</name>
<name sortKey="Wu, Jianming" sort="Wu, Jianming" uniqKey="Wu J" first="Jianming" last="Wu">Jianming Wu</name>
</country>
<country name="République populaire de Chine"><noRegion><name sortKey="Sun, Shihui" sort="Sun, Shihui" uniqKey="Sun S" first="Shihui" last="Sun">Shihui Sun</name>
</noRegion>
<name sortKey="Chen, Jing" sort="Chen, Jing" uniqKey="Chen J" first="Jing" last="Chen">Jing Chen</name>
<name sortKey="Chen, Yuehong" sort="Chen, Yuehong" uniqKey="Chen Y" first="Yuehong" last="Chen">Yuehong Chen</name>
<name sortKey="He, Lei" sort="He, Lei" uniqKey="He L" first="Lei" last="He">Lei He</name>
<name sortKey="Shi, Zhengli" sort="Shi, Zhengli" uniqKey="Shi Z" first="Zhengli" last="Shi">Zhengli Shi</name>
<name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name>
</country>
</tree>
</affiliations>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000141 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000141 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Sante
   |area=    MersV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     pubmed:31826992
   |texte=   Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry.
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:31826992" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a MersV1

This area was generated with Dilib version V0.6.33.
Data generation: Mon Apr 20 23:26:43 2020. Site generation: Sat Mar 27 09:06:09 2021

Serveur d'exploration MERS

Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry.

Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry.

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

	Serveur d'exploration MERS
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.