Serveur d'exploration MERS

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Host species restriction of Middle East respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4.

Identifieur interne : 001C37 ( Main/Exploration ); précédent : 001C36; suivant : 001C38

Host species restriction of Middle East respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4.

Auteurs : Neeltje Van Doremalen [États-Unis] ; Kerri L. Miazgowicz [États-Unis] ; Shauna Milne-Price [États-Unis] ; Trenton Bushmaker [États-Unis] ; Shelly Robertson [États-Unis] ; Dana Scott [États-Unis] ; Joerg Kinne [Émirats arabes unis] ; Jason S. Mclellan [États-Unis] ; Jiang Zhu [États-Unis] ; Vincent J. Munster

Source :

RBID : pubmed:24899185

Descripteurs français

English descriptors

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and ferret cells enabled MERS-CoV replication, whereas expression of hamster or ferret DPP4 did not. Modeling the binding energies of MERS-CoV spike protein RBD to DPP4 of human (susceptible) or hamster (nonsusceptible) identified five amino acid residues involved in the DPP4-RBD interaction. Expression of hamster DPP4 containing the five human DPP4 amino acids rendered BHK cells susceptible to MERS-CoV, whereas expression of human DPP4 containing the five hamster DPP4 amino acids did not. Using the same approach, the potential of MERS-CoV to utilize the DPP4s of common Middle Eastern livestock was investigated. Modeling of the DPP4 and MERS-CoV RBD interaction predicted the ability of MERS-CoV to bind the DPP4s of camel, goat, cow, and sheep. Expression of the DPP4s of these species on BHK cells supported MERS-CoV replication. This suggests, together with the abundant DPP4 presence in the respiratory tract, that these species might be able to function as a MERS-CoV intermediate reservoir.

DOI: 10.1128/JVI.00676-14
PubMed: 24899185


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Le document en format XML

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<name sortKey="Zhu, Jiang" sort="Zhu, Jiang" uniqKey="Zhu J" first="Jiang" last="Zhu">Jiang Zhu</name>
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<nlm:affiliation>Department of Immunology and Microbial Science and Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.</nlm:affiliation>
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<wicri:regionArea>Department of Immunology and Microbial Science and Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California</wicri:regionArea>
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<region type="state">Californie</region>
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<term>Animals</term>
<term>Camelus (metabolism)</term>
<term>Camelus (virology)</term>
<term>Cattle</term>
<term>Cell Line</term>
<term>Cell Line, Tumor</term>
<term>Coronavirus (metabolism)</term>
<term>Coronavirus (pathogenicity)</term>
<term>Cricetinae</term>
<term>Dipeptidyl Peptidase 4 (metabolism)</term>
<term>Ferrets (metabolism)</term>
<term>Ferrets (virology)</term>
<term>Goats (metabolism)</term>
<term>Goats (virology)</term>
<term>Host Specificity</term>
<term>Humans</term>
<term>Livestock (metabolism)</term>
<term>Livestock (virology)</term>
<term>Macaca mulatta (metabolism)</term>
<term>Macaca mulatta (virology)</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Middle East</term>
<term>Primates (metabolism)</term>
<term>Primates (virology)</term>
<term>Protein Binding</term>
<term>Receptors, Virus (metabolism)</term>
<term>Respiratory Syncytial Viruses (metabolism)</term>
<term>Respiratory Syncytial Viruses (pathogenicity)</term>
<term>Sheep (metabolism)</term>
<term>Sheep (virology)</term>
<term>Vero Cells</term>
<term>Viral Tropism</term>
<term>Virus Replication (genetics)</term>
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<term>Animaux</term>
<term>Bovins</term>
<term>Bétail (métabolisme)</term>
<term>Bétail (virologie)</term>
<term>Capra (métabolisme)</term>
<term>Capra (virologie)</term>
<term>Cellules Vero</term>
<term>Chameaux (métabolisme)</term>
<term>Chameaux (virologie)</term>
<term>Coronavirus (métabolisme)</term>
<term>Coronavirus (pathogénicité)</term>
<term>Cricetinae</term>
<term>Dipeptidyl peptidase 4 (métabolisme)</term>
<term>Furets (métabolisme)</term>
<term>Furets (virologie)</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Lignée cellulaire</term>
<term>Lignée cellulaire tumorale</term>
<term>Macaca mulatta (métabolisme)</term>
<term>Macaca mulatta (virologie)</term>
<term>Moyen Orient</term>
<term>Ovis (métabolisme)</term>
<term>Ovis (virologie)</term>
<term>Primates (métabolisme)</term>
<term>Primates (virologie)</term>
<term>Récepteurs viraux (métabolisme)</term>
<term>Réplication virale (génétique)</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Spécificité d'hôte</term>
<term>Tropisme viral</term>
<term>Virus respiratoires syncytiaux (métabolisme)</term>
<term>Virus respiratoires syncytiaux (pathogénicité)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Dipeptidyl Peptidase 4</term>
<term>Receptors, Virus</term>
</keywords>
<keywords scheme="MESH" type="geographic" xml:lang="en">
<term>Middle East</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Virus Replication</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Réplication virale</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Camelus</term>
<term>Coronavirus</term>
<term>Ferrets</term>
<term>Goats</term>
<term>Livestock</term>
<term>Macaca mulatta</term>
<term>Primates</term>
<term>Respiratory Syncytial Viruses</term>
<term>Sheep</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Bétail</term>
<term>Capra</term>
<term>Chameaux</term>
<term>Coronavirus</term>
<term>Dipeptidyl peptidase 4</term>
<term>Furets</term>
<term>Macaca mulatta</term>
<term>Ovis</term>
<term>Primates</term>
<term>Récepteurs viraux</term>
<term>Virus respiratoires syncytiaux</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en">
<term>Coronavirus</term>
<term>Respiratory Syncytial Viruses</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr">
<term>Coronavirus</term>
<term>Virus respiratoires syncytiaux</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr">
<term>Bétail</term>
<term>Capra</term>
<term>Chameaux</term>
<term>Furets</term>
<term>Macaca mulatta</term>
<term>Ovis</term>
<term>Primates</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en">
<term>Camelus</term>
<term>Ferrets</term>
<term>Goats</term>
<term>Livestock</term>
<term>Macaca mulatta</term>
<term>Primates</term>
<term>Sheep</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Cattle</term>
<term>Cell Line</term>
<term>Cell Line, Tumor</term>
<term>Cricetinae</term>
<term>Host Specificity</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Protein Binding</term>
<term>Vero Cells</term>
<term>Viral Tropism</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Animaux</term>
<term>Bovins</term>
<term>Cellules Vero</term>
<term>Cricetinae</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Lignée cellulaire</term>
<term>Lignée cellulaire tumorale</term>
<term>Moyen Orient</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Spécificité d'hôte</term>
<term>Tropisme viral</term>
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<front>
<div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and ferret cells enabled MERS-CoV replication, whereas expression of hamster or ferret DPP4 did not. Modeling the binding energies of MERS-CoV spike protein RBD to DPP4 of human (susceptible) or hamster (nonsusceptible) identified five amino acid residues involved in the DPP4-RBD interaction. Expression of hamster DPP4 containing the five human DPP4 amino acids rendered BHK cells susceptible to MERS-CoV, whereas expression of human DPP4 containing the five hamster DPP4 amino acids did not. Using the same approach, the potential of MERS-CoV to utilize the DPP4s of common Middle Eastern livestock was investigated. Modeling of the DPP4 and MERS-CoV RBD interaction predicted the ability of MERS-CoV to bind the DPP4s of camel, goat, cow, and sheep. Expression of the DPP4s of these species on BHK cells supported MERS-CoV replication. This suggests, together with the abundant DPP4 presence in the respiratory tract, that these species might be able to function as a MERS-CoV intermediate reservoir.</div>
</front>
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<country>
<li>Émirats arabes unis</li>
<li>États-Unis</li>
</country>
<region>
<li>Californie</li>
<li>Montana</li>
<li>New Hampshire</li>
</region>
</list>
<tree>
<noCountry>
<name sortKey="Munster, Vincent J" sort="Munster, Vincent J" uniqKey="Munster V" first="Vincent J" last="Munster">Vincent J. Munster</name>
</noCountry>
<country name="États-Unis">
<region name="Montana">
<name sortKey="Van Doremalen, Neeltje" sort="Van Doremalen, Neeltje" uniqKey="Van Doremalen N" first="Neeltje" last="Van Doremalen">Neeltje Van Doremalen</name>
</region>
<name sortKey="Bushmaker, Trenton" sort="Bushmaker, Trenton" uniqKey="Bushmaker T" first="Trenton" last="Bushmaker">Trenton Bushmaker</name>
<name sortKey="Mclellan, Jason S" sort="Mclellan, Jason S" uniqKey="Mclellan J" first="Jason S" last="Mclellan">Jason S. Mclellan</name>
<name sortKey="Miazgowicz, Kerri L" sort="Miazgowicz, Kerri L" uniqKey="Miazgowicz K" first="Kerri L" last="Miazgowicz">Kerri L. Miazgowicz</name>
<name sortKey="Milne Price, Shauna" sort="Milne Price, Shauna" uniqKey="Milne Price S" first="Shauna" last="Milne-Price">Shauna Milne-Price</name>
<name sortKey="Robertson, Shelly" sort="Robertson, Shelly" uniqKey="Robertson S" first="Shelly" last="Robertson">Shelly Robertson</name>
<name sortKey="Scott, Dana" sort="Scott, Dana" uniqKey="Scott D" first="Dana" last="Scott">Dana Scott</name>
<name sortKey="Zhu, Jiang" sort="Zhu, Jiang" uniqKey="Zhu J" first="Jiang" last="Zhu">Jiang Zhu</name>
</country>
<country name="Émirats arabes unis">
<noRegion>
<name sortKey="Kinne, Joerg" sort="Kinne, Joerg" uniqKey="Kinne J" first="Joerg" last="Kinne">Joerg Kinne</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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