Serveur d'exploration MERS

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Adaptive Evolution of MERS-CoV to Species Variation in DPP4.

Identifieur interne : 000813 ( PubMed/Curation ); précédent : 000812; suivant : 000814

Adaptive Evolution of MERS-CoV to Species Variation in DPP4.

Auteurs : Michael Letko [États-Unis] ; Kerri Miazgowicz [États-Unis] ; Rebekah Mcminn [États-Unis] ; Stephanie N. Seifert [États-Unis] ; Isabel Sola [Espagne] ; Luis Enjuanes [Espagne] ; Aaron Carmody [États-Unis] ; Neeltje Van Doremalen [États-Unis] ; Vincent Munster [États-Unis]

Source :

RBID : pubmed:30110630

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English descriptors

Abstract

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) likely originated in bats and passed to humans through dromedary camels; however, the genetic mechanisms underlying cross-species adaptation remain poorly understood. Variation in the host receptor, dipeptidyl peptidase 4 (DPP4), can block the interaction with the MERS-CoV spike protein and form a species barrier to infection. To better understand the species adaptability of MERS-CoV, we identified a suboptimal species-derived variant of DPP4 to study viral adaption. Passaging virus on cells expressing this DPP4 variant led to accumulation of mutations in the viral spike which increased replication. Parallel passages revealed distinct paths of viral adaptation to the same DPP4 variant. Structural analysis and functional assays showed that these mutations enhanced viral entry with suboptimal DPP4 by altering the surface charge of spike. These findings demonstrate that MERS-CoV spike can utilize multiple paths to rapidly adapt to novel species variation in DPP4.

DOI: 10.1016/j.celrep.2018.07.045
PubMed: 30110630

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Le document en format XML

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<term>Adaptation, Physiological</term>
<term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Binding Sites</term>
<term>Biological Coevolution</term>
<term>Chiroptera</term>
<term>Chlorocebus aethiops</term>
<term>Cricetulus</term>
<term>Dipeptidyl Peptidase 4 (chemistry)</term>
<term>Dipeptidyl Peptidase 4 (genetics)</term>
<term>Dipeptidyl Peptidase 4 (metabolism)</term>
<term>Gene Expression</term>
<term>Host Specificity</term>
<term>Host-Pathogen Interactions (genetics)</term>
<term>Humans</term>
<term>Middle East Respiratory Syndrome Coronavirus (genetics)</term>
<term>Middle East Respiratory Syndrome Coronavirus (metabolism)</term>
<term>Models, Molecular</term>
<term>Mutation</term>
<term>Protein Binding</term>
<term>Protein Conformation, alpha-Helical</term>
<term>Protein Conformation, beta-Strand</term>
<term>Protein Interaction Domains and Motifs</term>
<term>Receptors, Virus (chemistry)</term>
<term>Receptors, Virus (genetics)</term>
<term>Receptors, Virus (metabolism)</term>
<term>Sequence Alignment</term>
<term>Sequence Homology, Amino Acid</term>
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<term>Spike Glycoprotein, Coronavirus (genetics)</term>
<term>Spike Glycoprotein, Coronavirus (metabolism)</term>
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<term>Adaptation physiologique</term>
<term>Alignement de séquences</term>
<term>Animaux</term>
<term>Cellules Vero</term>
<term>Chiroptera</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (génétique)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (métabolisme)</term>
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<term>Dipeptidyl peptidase 4 ()</term>
<term>Dipeptidyl peptidase 4 (génétique)</term>
<term>Dipeptidyl peptidase 4 (métabolisme)</term>
<term>Expression des gènes</term>
<term>Glycoprotéine de spicule des coronavirus ()</term>
<term>Glycoprotéine de spicule des coronavirus (génétique)</term>
<term>Glycoprotéine de spicule des coronavirus (métabolisme)</term>
<term>Humains</term>
<term>Interactions hôte-pathogène (génétique)</term>
<term>Liaison aux protéines</term>
<term>Modèles moléculaires</term>
<term>Motifs et domaines d'intéraction protéique</term>
<term>Mutation</term>
<term>Pénétration virale</term>
<term>Récepteurs viraux ()</term>
<term>Récepteurs viraux (génétique)</term>
<term>Récepteurs viraux (métabolisme)</term>
<term>Similitude de séquences d'acides aminés</term>
<term>Sites de fixation</term>
<term>Spécificité d'hôte</term>
<term>Structure en brin bêta</term>
<term>Structure en hélice alpha</term>
<term>Séquence d'acides aminés</term>
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<term>Dipeptidyl Peptidase 4</term>
<term>Receptors, Virus</term>
<term>Spike Glycoprotein, Coronavirus</term>
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<term>Receptors, Virus</term>
<term>Spike Glycoprotein, Coronavirus</term>
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<term>Spike Glycoprotein, Coronavirus</term>
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<term>Host-Pathogen Interactions</term>
<term>Middle East Respiratory Syndrome Coronavirus</term>
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<term>Dipeptidyl peptidase 4</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Interactions hôte-pathogène</term>
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<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Dipeptidyl peptidase 4</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Récepteurs viraux</term>
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<term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Binding Sites</term>
<term>Biological Coevolution</term>
<term>Chiroptera</term>
<term>Chlorocebus aethiops</term>
<term>Cricetulus</term>
<term>Gene Expression</term>
<term>Host Specificity</term>
<term>Humans</term>
<term>Models, Molecular</term>
<term>Mutation</term>
<term>Protein Binding</term>
<term>Protein Conformation, alpha-Helical</term>
<term>Protein Conformation, beta-Strand</term>
<term>Protein Interaction Domains and Motifs</term>
<term>Sequence Alignment</term>
<term>Sequence Homology, Amino Acid</term>
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<term>Virus Internalization</term>
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<term>Adaptation physiologique</term>
<term>Alignement de séquences</term>
<term>Animaux</term>
<term>Cellules Vero</term>
<term>Chiroptera</term>
<term>Cricetulus</term>
<term>Dipeptidyl peptidase 4</term>
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<term>Glycoprotéine de spicule des coronavirus</term>
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<term>Modèles moléculaires</term>
<term>Motifs et domaines d'intéraction protéique</term>
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<term>Récepteurs viraux</term>
<term>Similitude de séquences d'acides aminés</term>
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<term>Structure en brin bêta</term>
<term>Structure en hélice alpha</term>
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<front>
<div type="abstract" xml:lang="en">Middle East Respiratory Syndrome Coronavirus (MERS-CoV) likely originated in bats and passed to humans through dromedary camels; however, the genetic mechanisms underlying cross-species adaptation remain poorly understood. Variation in the host receptor, dipeptidyl peptidase 4 (DPP4), can block the interaction with the MERS-CoV spike protein and form a species barrier to infection. To better understand the species adaptability of MERS-CoV, we identified a suboptimal species-derived variant of DPP4 to study viral adaption. Passaging virus on cells expressing this DPP4 variant led to accumulation of mutations in the viral spike which increased replication. Parallel passages revealed distinct paths of viral adaptation to the same DPP4 variant. Structural analysis and functional assays showed that these mutations enhanced viral entry with suboptimal DPP4 by altering the surface charge of spike. These findings demonstrate that MERS-CoV spike can utilize multiple paths to rapidly adapt to novel species variation in DPP4.</div>
</front>
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<Title>Cell reports</Title>
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<Abstract>
<AbstractText>Middle East Respiratory Syndrome Coronavirus (MERS-CoV) likely originated in bats and passed to humans through dromedary camels; however, the genetic mechanisms underlying cross-species adaptation remain poorly understood. Variation in the host receptor, dipeptidyl peptidase 4 (DPP4), can block the interaction with the MERS-CoV spike protein and form a species barrier to infection. To better understand the species adaptability of MERS-CoV, we identified a suboptimal species-derived variant of DPP4 to study viral adaption. Passaging virus on cells expressing this DPP4 variant led to accumulation of mutations in the viral spike which increased replication. Parallel passages revealed distinct paths of viral adaptation to the same DPP4 variant. Structural analysis and functional assays showed that these mutations enhanced viral entry with suboptimal DPP4 by altering the surface charge of spike. These findings demonstrate that MERS-CoV spike can utilize multiple paths to rapidly adapt to novel species variation in DPP4.</AbstractText>
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