Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein.
Identifieur interne : 000D48 ( Main/Exploration ); précédent : 000D47; suivant : 000D49Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein.
Auteurs : Wentao Li [Pays-Bas] ; Ruben J G. Hulswit [Pays-Bas] ; Ivy Widjaja [Pays-Bas] ; V Stalin Raj [Pays-Bas] ; Ryan Mcbride [États-Unis] ; Wenjie Peng [États-Unis] ; W. Widagdo [Pays-Bas] ; M Alejandra Tortorici [France] ; Brenda Van Dieren [Pays-Bas] ; Yifei Lang [Pays-Bas] ; Jan W M. Van Lent [Pays-Bas] ; James C. Paulson [États-Unis] ; Cornelis A M. De Haan [Pays-Bas] ; Raoul J. De Groot [Pays-Bas] ; Frank J M. Van Kuppeveld [Pays-Bas] ; Bart L. Haagmans [Pays-Bas] ; Berend-Jan Bosch [Pays-Bas]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 1091-6490 ] ; 2017.
Descripteurs français
- KwdFr :
- Acides sialiques (métabolisme), Animaux, Attachement viral, Chameaux, Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité), Dipeptidyl peptidase 4 (génétique), Dipeptidyl peptidase 4 (métabolisme), Glycoprotéine de spicule des coronavirus (génétique), Glycoprotéine de spicule des coronavirus (métabolisme), Humains, Infections à coronavirus (métabolisme), Infections à coronavirus (virologie), Mucines, Polyosides (métabolisme), Récepteurs viraux (métabolisme).
- MESH :
- génétique : Dipeptidyl peptidase 4, Glycoprotéine de spicule des coronavirus.
- métabolisme : Acides sialiques, Dipeptidyl peptidase 4, Glycoprotéine de spicule des coronavirus, Infections à coronavirus, Polyosides, Récepteurs viraux.
- pathogénicité : Coronavirus du syndrome respiratoire du Moyen-Orient.
- virologie : Infections à coronavirus.
- Animaux, Attachement viral, Chameaux, Humains, Mucines.
English descriptors
- KwdEn :
- Animals, Camelus, Coronavirus Infections (metabolism), Coronavirus Infections (virology), Dipeptidyl Peptidase 4 (genetics), Dipeptidyl Peptidase 4 (metabolism), Humans, Middle East Respiratory Syndrome Coronavirus (pathogenicity), Mucins, Polysaccharides (metabolism), Receptors, Virus (metabolism), Sialic Acids (metabolism), Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (metabolism), Virus Attachment.
- MESH :
- chemical , genetics : Dipeptidyl Peptidase 4, Spike Glycoprotein, Coronavirus.
- metabolism : Coronavirus Infections, Dipeptidyl Peptidase 4, Polysaccharides, Receptors, Virus, Sialic Acids, Spike Glycoprotein, Coronavirus.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- virology : Coronavirus Infections.
- Animals, Camelus, Humans, Mucins, Virus Attachment.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) targets the epithelial cells of the respiratory tract both in humans and in its natural host, the dromedary camel. Virion attachment to host cells is mediated by 20-nm-long homotrimers of spike envelope protein S. The N-terminal subunit of each S protomer, called S1, folds into four distinct domains designated S1A through S1D Binding of MERS-CoV to the cell surface entry receptor dipeptidyl peptidase 4 (DPP4) occurs via S1B We now demonstrate that in addition to DPP4, MERS-CoV binds to sialic acid (Sia). Initially demonstrated by hemagglutination assay with human erythrocytes and intact virus, MERS-CoV Sia-binding activity was assigned to S subdomain S1A When multivalently displayed on nanoparticles, S1 or S1A bound to human erythrocytes and to human mucin in a strictly Sia-dependent fashion. Glycan array analysis revealed a preference for α2,3-linked Sias over α2,6-linked Sias, which correlates with the differential distribution of α2,3-linked Sias and the predominant sites of MERS-CoV replication in the upper and lower respiratory tracts of camels and humans, respectively. Binding is hampered by Sia modifications such as 5-N-glycolylation and (7,)9-O-acetylation. Depletion of cell surface Sia by neuraminidase treatment inhibited MERS-CoV entry of Calu-3 human airway cells, thus providing direct evidence that virus-Sia interactions may aid in virion attachment. The combined observations lead us to propose that high-specificity, low-affinity attachment of MERS-CoV to sialoglycans during the preattachment or early attachment phase may form another determinant governing the host range and tissue tropism of this zoonotic pathogen.
DOI: 10.1073/pnas.1712592114
PubMed: 28923942
Affiliations:
- France, Pays-Bas, États-Unis
- Californie, Gueldre (province), Utrecht (province), Île-de-France
- Paris, Utrecht, Wageningue
- Université d'Utrecht, Université de Wageningue
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Le document en format XML
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Widagdo</name><affiliation wicri:level="1"><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Viroscience, Erasmus Medical Center, 3015 CN Rotterdam</wicri:regionArea><wicri:noRegion>3015 CN Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Tortorici, M Alejandra" sort="Tortorici, M Alejandra" uniqKey="Tortorici M" first="M Alejandra" last="Tortorici">M Alejandra Tortorici</name><affiliation wicri:level="3"><nlm:affiliation>Institut Pasteur, Unité de Virologie Structurale, 75015 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, Unité de Virologie Structurale, 75015 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Van Dieren, Brenda" sort="Van Dieren, Brenda" uniqKey="Van Dieren B" first="Brenda" last="Van Dieren">Brenda Van Dieren</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht</wicri:regionArea><orgName type="university">Université d'Utrecht</orgName><placeName><settlement type="city">Utrecht</settlement><region nuts="2">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Lang, Yifei" sort="Lang, Yifei" uniqKey="Lang Y" first="Yifei" last="Lang">Yifei Lang</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht</wicri:regionArea><orgName type="university">Université d'Utrecht</orgName><placeName><settlement type="city">Utrecht</settlement><region nuts="2">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Van Lent, Jan W M" sort="Van Lent, Jan W M" uniqKey="Van Lent J" first="Jan W M" last="Van Lent">Jan W M. 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Paulson</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla</wicri:cityArea></affiliation></author><author><name sortKey="De Haan, Cornelis A M" sort="De Haan, Cornelis A M" uniqKey="De Haan C" first="Cornelis A M" last="De Haan">Cornelis A M. De Haan</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht</wicri:regionArea><orgName type="university">Université d'Utrecht</orgName><placeName><settlement type="city">Utrecht</settlement><region nuts="2">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="De Groot, Raoul J" sort="De Groot, Raoul J" uniqKey="De Groot R" first="Raoul J" last="De Groot">Raoul J. De Groot</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht</wicri:regionArea><orgName type="university">Université d'Utrecht</orgName><placeName><settlement type="city">Utrecht</settlement><region nuts="2">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Van Kuppeveld, Frank J M" sort="Van Kuppeveld, Frank J M" uniqKey="Van Kuppeveld F" first="Frank J M" last="Van Kuppeveld">Frank J M. Van Kuppeveld</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht</wicri:regionArea><orgName type="university">Université d'Utrecht</orgName><placeName><settlement type="city">Utrecht</settlement><region nuts="2">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Haagmans, Bart L" sort="Haagmans, Bart L" uniqKey="Haagmans B" first="Bart L" last="Haagmans">Bart L. Haagmans</name><affiliation wicri:level="1"><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands; b.haagmans@erasmusmc.nl b.j.bosch@uu.nl.</nlm:affiliation><country wicri:rule="url">Pays-Bas</country><wicri:regionArea>Department of Viroscience, Erasmus Medical Center, 3015 CN Rotterdam</wicri:regionArea><wicri:noRegion>3015 CN Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Bosch, Berend Jan" sort="Bosch, Berend Jan" uniqKey="Bosch B" first="Berend-Jan" last="Bosch">Berend-Jan Bosch</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands; b.haagmans@erasmusmc.nl b.j.bosch@uu.nl.</nlm:affiliation><country wicri:rule="url">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht</wicri:regionArea><orgName type="university">Université d'Utrecht</orgName><placeName><settlement type="city">Utrecht</settlement><region nuts="2">Utrecht (province)</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28923942</idno><idno type="pmid">28923942</idno><idno type="doi">10.1073/pnas.1712592114</idno><idno type="wicri:Area/PubMed/Corpus">000B48</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000B48</idno><idno type="wicri:Area/PubMed/Curation">000B48</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000B48</idno><idno type="wicri:Area/PubMed/Checkpoint">000C69</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000C69</idno><idno type="wicri:Area/Ncbi/Merge">001B84</idno><idno type="wicri:Area/Ncbi/Curation">001B84</idno><idno type="wicri:Area/Ncbi/Checkpoint">001B84</idno><idno type="wicri:Area/Main/Merge">000D51</idno><idno type="wicri:Area/Main/Curation">000D48</idno><idno type="wicri:Area/Main/Exploration">000D48</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein.</title><author><name sortKey="Li, Wentao" sort="Li, Wentao" uniqKey="Li W" first="Wentao" last="Li">Wentao Li</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht</wicri:regionArea><orgName type="university">Université d'Utrecht</orgName><placeName><settlement type="city">Utrecht</settlement><region nuts="2">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Hulswit, Ruben J G" sort="Hulswit, Ruben J G" uniqKey="Hulswit R" first="Ruben J G" last="Hulswit">Ruben J G. Hulswit</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht</wicri:regionArea><orgName type="university">Université d'Utrecht</orgName><placeName><settlement type="city">Utrecht</settlement><region nuts="2">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Widjaja, Ivy" sort="Widjaja, Ivy" uniqKey="Widjaja I" first="Ivy" last="Widjaja">Ivy Widjaja</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht</wicri:regionArea><orgName type="university">Université d'Utrecht</orgName><placeName><settlement type="city">Utrecht</settlement><region nuts="2">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Raj, V Stalin" sort="Raj, V Stalin" uniqKey="Raj V" first="V Stalin" last="Raj">V Stalin Raj</name><affiliation wicri:level="1"><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Viroscience, Erasmus Medical Center, 3015 CN Rotterdam</wicri:regionArea><wicri:noRegion>3015 CN Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Mcbride, Ryan" sort="Mcbride, Ryan" uniqKey="Mcbride R" first="Ryan" last="Mcbride">Ryan Mcbride</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla</wicri:cityArea></affiliation></author><author><name sortKey="Peng, Wenjie" sort="Peng, Wenjie" uniqKey="Peng W" first="Wenjie" last="Peng">Wenjie Peng</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla</wicri:cityArea></affiliation></author><author><name sortKey="Widagdo, W" sort="Widagdo, W" uniqKey="Widagdo W" first="W" last="Widagdo">W. Widagdo</name><affiliation wicri:level="1"><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Viroscience, Erasmus Medical Center, 3015 CN Rotterdam</wicri:regionArea><wicri:noRegion>3015 CN Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Tortorici, M Alejandra" sort="Tortorici, M Alejandra" uniqKey="Tortorici M" first="M Alejandra" last="Tortorici">M Alejandra Tortorici</name><affiliation wicri:level="3"><nlm:affiliation>Institut Pasteur, Unité de Virologie Structurale, 75015 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, Unité de Virologie Structurale, 75015 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Van Dieren, Brenda" sort="Van Dieren, Brenda" uniqKey="Van Dieren B" first="Brenda" last="Van Dieren">Brenda Van Dieren</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht</wicri:regionArea><orgName type="university">Université d'Utrecht</orgName><placeName><settlement type="city">Utrecht</settlement><region nuts="2">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Lang, Yifei" sort="Lang, Yifei" uniqKey="Lang Y" first="Yifei" last="Lang">Yifei Lang</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht</wicri:regionArea><orgName type="university">Université d'Utrecht</orgName><placeName><settlement type="city">Utrecht</settlement><region nuts="2">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Van Lent, Jan W M" sort="Van Lent, Jan W M" uniqKey="Van Lent J" first="Jan W M" last="Van Lent">Jan W M. Van Lent</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology, Department of Plant Sciences, Wageningen University, 6708 PB Wageningen, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Laboratory of Virology, Department of Plant Sciences, Wageningen University, 6708 PB Wageningen</wicri:regionArea><orgName type="university">Université de Wageningue</orgName><placeName><settlement type="city">Wageningue</settlement><region nuts="2">Gueldre (province)</region></placeName></affiliation></author><author><name sortKey="Paulson, James C" sort="Paulson, James C" uniqKey="Paulson J" first="James C" last="Paulson">James C. Paulson</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla</wicri:cityArea></affiliation></author><author><name sortKey="De Haan, Cornelis A M" sort="De Haan, Cornelis A M" uniqKey="De Haan C" first="Cornelis A M" last="De Haan">Cornelis A M. De Haan</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht</wicri:regionArea><orgName type="university">Université d'Utrecht</orgName><placeName><settlement type="city">Utrecht</settlement><region nuts="2">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="De Groot, Raoul J" sort="De Groot, Raoul J" uniqKey="De Groot R" first="Raoul J" last="De Groot">Raoul J. De Groot</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht</wicri:regionArea><orgName type="university">Université d'Utrecht</orgName><placeName><settlement type="city">Utrecht</settlement><region nuts="2">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Van Kuppeveld, Frank J M" sort="Van Kuppeveld, Frank J M" uniqKey="Van Kuppeveld F" first="Frank J M" last="Van Kuppeveld">Frank J M. Van Kuppeveld</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht</wicri:regionArea><orgName type="university">Université d'Utrecht</orgName><placeName><settlement type="city">Utrecht</settlement><region nuts="2">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Haagmans, Bart L" sort="Haagmans, Bart L" uniqKey="Haagmans B" first="Bart L" last="Haagmans">Bart L. Haagmans</name><affiliation wicri:level="1"><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands; b.haagmans@erasmusmc.nl b.j.bosch@uu.nl.</nlm:affiliation><country wicri:rule="url">Pays-Bas</country><wicri:regionArea>Department of Viroscience, Erasmus Medical Center, 3015 CN Rotterdam</wicri:regionArea><wicri:noRegion>3015 CN Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Bosch, Berend Jan" sort="Bosch, Berend Jan" uniqKey="Bosch B" first="Berend-Jan" last="Bosch">Berend-Jan Bosch</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands; b.haagmans@erasmusmc.nl b.j.bosch@uu.nl.</nlm:affiliation><country wicri:rule="url">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht</wicri:regionArea><orgName type="university">Université d'Utrecht</orgName><placeName><settlement type="city">Utrecht</settlement><region nuts="2">Utrecht (province)</region></placeName></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="eISSN">1091-6490</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Camelus</term><term>Coronavirus Infections (metabolism)</term><term>Coronavirus Infections (virology)</term><term>Dipeptidyl Peptidase 4 (genetics)</term><term>Dipeptidyl Peptidase 4 (metabolism)</term><term>Humans</term><term>Middle East Respiratory Syndrome Coronavirus (pathogenicity)</term><term>Mucins</term><term>Polysaccharides (metabolism)</term><term>Receptors, Virus (metabolism)</term><term>Sialic Acids (metabolism)</term><term>Spike Glycoprotein, Coronavirus (genetics)</term><term>Spike Glycoprotein, Coronavirus (metabolism)</term><term>Virus Attachment</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acides sialiques (métabolisme)</term><term>Animaux</term><term>Attachement viral</term><term>Chameaux</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité)</term><term>Dipeptidyl peptidase 4 (génétique)</term><term>Dipeptidyl peptidase 4 (métabolisme)</term><term>Glycoprotéine de spicule des coronavirus (génétique)</term><term>Glycoprotéine de spicule des coronavirus (métabolisme)</term><term>Humains</term><term>Infections à coronavirus (métabolisme)</term><term>Infections à coronavirus (virologie)</term><term>Mucines</term><term>Polyosides (métabolisme)</term><term>Récepteurs viraux (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Dipeptidyl Peptidase 4</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Dipeptidyl peptidase 4</term><term>Glycoprotéine de spicule des coronavirus</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Coronavirus Infections</term><term>Dipeptidyl Peptidase 4</term><term>Polysaccharides</term><term>Receptors, Virus</term><term>Sialic Acids</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Acides sialiques</term><term>Dipeptidyl peptidase 4</term><term>Glycoprotéine de spicule des coronavirus</term><term>Infections à coronavirus</term><term>Polyosides</term><term>Récepteurs viraux</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="virologie" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Camelus</term><term>Humans</term><term>Mucins</term><term>Virus Attachment</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Attachement viral</term><term>Chameaux</term><term>Humains</term><term>Mucines</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) targets the epithelial cells of the respiratory tract both in humans and in its natural host, the dromedary camel. Virion attachment to host cells is mediated by 20-nm-long homotrimers of spike envelope protein S. The N-terminal subunit of each S protomer, called S1, folds into four distinct domains designated S1<sup>A</sup> through S1<sup>D</sup> Binding of MERS-CoV to the cell surface entry receptor dipeptidyl peptidase 4 (DPP4) occurs via S1<sup>B</sup> We now demonstrate that in addition to DPP4, MERS-CoV binds to sialic acid (Sia). Initially demonstrated by hemagglutination assay with human erythrocytes and intact virus, MERS-CoV Sia-binding activity was assigned to S subdomain S1<sup>A</sup> When multivalently displayed on nanoparticles, S1 or S1<sup>A</sup> bound to human erythrocytes and to human mucin in a strictly Sia-dependent fashion. Glycan array analysis revealed a preference for α2,3-linked Sias over α2,6-linked Sias, which correlates with the differential distribution of α2,3-linked Sias and the predominant sites of MERS-CoV replication in the upper and lower respiratory tracts of camels and humans, respectively. Binding is hampered by Sia modifications such as 5-<i>N</i>-glycolylation and (7,)9-<i>O</i>-acetylation. Depletion of cell surface Sia by neuraminidase treatment inhibited MERS-CoV entry of Calu-3 human airway cells, thus providing direct evidence that virus-Sia interactions may aid in virion attachment. The combined observations lead us to propose that high-specificity, low-affinity attachment of MERS-CoV to sialoglycans during the preattachment or early attachment phase may form another determinant governing the host range and tissue tropism of this zoonotic pathogen.</div></front></TEI><affiliations><list><country><li>France</li><li>Pays-Bas</li><li>États-Unis</li></country><region><li>Californie</li><li>Gueldre (province)</li><li>Utrecht (province)</li><li>Île-de-France</li></region><settlement><li>Paris</li><li>Utrecht</li><li>Wageningue</li></settlement><orgName><li>Université d'Utrecht</li><li>Université de Wageningue</li></orgName></list><tree><country name="Pays-Bas"><region name="Utrecht (province)"><name sortKey="Li, Wentao" sort="Li, Wentao" uniqKey="Li W" first="Wentao" last="Li">Wentao Li</name></region><name sortKey="Bosch, Berend Jan" sort="Bosch, Berend Jan" uniqKey="Bosch B" first="Berend-Jan" last="Bosch">Berend-Jan Bosch</name><name sortKey="De Groot, Raoul J" sort="De Groot, Raoul J" uniqKey="De Groot R" first="Raoul J" last="De Groot">Raoul J. De Groot</name><name sortKey="De Haan, Cornelis A M" sort="De Haan, Cornelis A M" uniqKey="De Haan C" first="Cornelis A M" last="De Haan">Cornelis A M. De Haan</name><name sortKey="Haagmans, Bart L" sort="Haagmans, Bart L" uniqKey="Haagmans B" first="Bart L" last="Haagmans">Bart L. Haagmans</name><name sortKey="Hulswit, Ruben J G" sort="Hulswit, Ruben J G" uniqKey="Hulswit R" first="Ruben J G" last="Hulswit">Ruben J G. Hulswit</name><name sortKey="Lang, Yifei" sort="Lang, Yifei" uniqKey="Lang Y" first="Yifei" last="Lang">Yifei Lang</name><name sortKey="Raj, V Stalin" sort="Raj, V Stalin" uniqKey="Raj V" first="V Stalin" last="Raj">V Stalin Raj</name><name sortKey="Van Dieren, Brenda" sort="Van Dieren, Brenda" uniqKey="Van Dieren B" first="Brenda" last="Van Dieren">Brenda Van Dieren</name><name sortKey="Van Kuppeveld, Frank J M" sort="Van Kuppeveld, Frank J M" uniqKey="Van Kuppeveld F" first="Frank J M" last="Van Kuppeveld">Frank J M. Van Kuppeveld</name><name sortKey="Van Lent, Jan W M" sort="Van Lent, Jan W M" uniqKey="Van Lent J" first="Jan W M" last="Van Lent">Jan W M. Van Lent</name><name sortKey="Widagdo, W" sort="Widagdo, W" uniqKey="Widagdo W" first="W" last="Widagdo">W. Widagdo</name><name sortKey="Widjaja, Ivy" sort="Widjaja, Ivy" uniqKey="Widjaja I" first="Ivy" last="Widjaja">Ivy Widjaja</name></country><country name="États-Unis"><region name="Californie"><name sortKey="Mcbride, Ryan" sort="Mcbride, Ryan" uniqKey="Mcbride R" first="Ryan" last="Mcbride">Ryan Mcbride</name></region><name sortKey="Paulson, James C" sort="Paulson, James C" uniqKey="Paulson J" first="James C" last="Paulson">James C. Paulson</name><name sortKey="Peng, Wenjie" sort="Peng, Wenjie" uniqKey="Peng W" first="Wenjie" last="Peng">Wenjie Peng</name></country><country name="France"><region name="Île-de-France"><name sortKey="Tortorici, M Alejandra" sort="Tortorici, M Alejandra" uniqKey="Tortorici M" first="M Alejandra" last="Tortorici">M Alejandra Tortorici</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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