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A single asparagine-linked glycosylation site of the severe acute respiratory syndrome coronavirus spike glycoprotein facilitates inhibition by mannose-binding lectin through multiple mechanisms.

Identifieur interne : 002589 ( Main/Exploration ); précédent : 002588; suivant : 002590

A single asparagine-linked glycosylation site of the severe acute respiratory syndrome coronavirus spike glycoprotein facilitates inhibition by mannose-binding lectin through multiple mechanisms.

Auteurs : Yanchen Zhou [États-Unis] ; Kai Lu ; Susanne Pfefferle ; Stephanie Bertram ; Ilona Glowacka ; Christian Drosten ; Stefan Pöhlmann ; Graham Simmons

Source :

RBID : pubmed:20573835

Descripteurs français

English descriptors

Abstract

Mannose-binding lectin (MBL) is a serum protein that plays an important role in host defenses as an opsonin and through activation of the complement system. The objective of this study was to assess the interactions between MBL and severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) glycoprotein (SARS-S). MBL was found to selectively bind to retroviral particles pseudotyped with SARS-S. Unlike several other viral envelopes to which MBL can bind, both recombinant and plasma-derived human MBL directly inhibited SARS-S-mediated viral infection. Moreover, the interaction between MBL and SARS-S blocked viral binding to the C-type lectin, DC-SIGN. Mutagenesis indicated that a single N-linked glycosylation site, N330, was critical for the specific interactions between MBL and SARS-S. Despite the proximity of N330 to the receptor-binding motif of SARS-S, MBL did not affect interactions with the ACE2 receptor or cathepsin L-mediated activation of SARS-S-driven membrane fusion. Thus, binding of MBL to SARS-S may interfere with other early pre- or postreceptor-binding events necessary for efficient viral entry.

DOI: 10.1128/JVI.00554-10
PubMed: 20573835


Affiliations:


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Le document en format XML

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<name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name>
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<term>Aged</term>
<term>Amino Acid Motifs</term>
<term>Asparagine (genetics)</term>
<term>Asparagine (metabolism)</term>
<term>Cell Adhesion Molecules (genetics)</term>
<term>Cell Adhesion Molecules (metabolism)</term>
<term>Cell Line</term>
<term>Glycosylation</term>
<term>Humans</term>
<term>Lectins, C-Type (genetics)</term>
<term>Lectins, C-Type (metabolism)</term>
<term>Male</term>
<term>Mannose-Binding Lectin (genetics)</term>
<term>Mannose-Binding Lectin (metabolism)</term>
<term>Membrane Glycoproteins (chemistry)</term>
<term>Membrane Glycoproteins (genetics)</term>
<term>Membrane Glycoproteins (metabolism)</term>
<term>Middle Aged</term>
<term>Protein Binding</term>
<term>Receptors, Cell Surface (genetics)</term>
<term>Receptors, Cell Surface (metabolism)</term>
<term>SARS Virus (chemistry)</term>
<term>SARS Virus (genetics)</term>
<term>SARS Virus (metabolism)</term>
<term>Severe Acute Respiratory Syndrome (metabolism)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Viral Envelope Proteins (chemistry)</term>
<term>Viral Envelope Proteins (genetics)</term>
<term>Viral Envelope Proteins (metabolism)</term>
<term>Young Adult</term>
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<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Asparagine (génétique)</term>
<term>Asparagine (métabolisme)</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires ()</term>
<term>Glycoprotéines membranaires (génétique)</term>
<term>Glycoprotéines membranaires (métabolisme)</term>
<term>Glycosylation</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Lectine liant le mannose (génétique)</term>
<term>Lectine liant le mannose (métabolisme)</term>
<term>Lectines de type C (génétique)</term>
<term>Lectines de type C (métabolisme)</term>
<term>Liaison aux protéines</term>
<term>Lignée cellulaire</term>
<term>Molécules d'adhérence cellulaire (génétique)</term>
<term>Molécules d'adhérence cellulaire (métabolisme)</term>
<term>Motifs d'acides aminés</term>
<term>Mâle</term>
<term>Protéines de l'enveloppe virale ()</term>
<term>Protéines de l'enveloppe virale (génétique)</term>
<term>Protéines de l'enveloppe virale (métabolisme)</term>
<term>Récepteurs de surface cellulaire (génétique)</term>
<term>Récepteurs de surface cellulaire (métabolisme)</term>
<term>Sujet âgé</term>
<term>Syndrome respiratoire aigu sévère (métabolisme)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Virus du SRAS ()</term>
<term>Virus du SRAS (génétique)</term>
<term>Virus du SRAS (métabolisme)</term>
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<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en">
<term>Membrane Glycoproteins</term>
<term>Viral Envelope Proteins</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>Asparagine</term>
<term>Cell Adhesion Molecules</term>
<term>Lectins, C-Type</term>
<term>Mannose-Binding Lectin</term>
<term>Membrane Glycoproteins</term>
<term>Receptors, Cell Surface</term>
<term>Viral Envelope Proteins</term>
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<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Asparagine</term>
<term>Cell Adhesion Molecules</term>
<term>Lectins, C-Type</term>
<term>Mannose-Binding Lectin</term>
<term>Membrane Glycoproteins</term>
<term>Receptors, Cell Surface</term>
<term>Viral Envelope Proteins</term>
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<keywords scheme="MESH" qualifier="chemistry" xml:lang="en">
<term>SARS Virus</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>SARS Virus</term>
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<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Asparagine</term>
<term>Glycoprotéines membranaires</term>
<term>Lectine liant le mannose</term>
<term>Lectines de type C</term>
<term>Molécules d'adhérence cellulaire</term>
<term>Protéines de l'enveloppe virale</term>
<term>Récepteurs de surface cellulaire</term>
<term>Virus du SRAS</term>
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<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>SARS Virus</term>
<term>Severe Acute Respiratory Syndrome</term>
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<term>Asparagine</term>
<term>Glycoprotéines membranaires</term>
<term>Lectine liant le mannose</term>
<term>Lectines de type C</term>
<term>Molécules d'adhérence cellulaire</term>
<term>Protéines de l'enveloppe virale</term>
<term>Récepteurs de surface cellulaire</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Virus du SRAS</term>
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<term>Syndrome respiratoire aigu sévère</term>
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<keywords scheme="MESH" qualifier="virology" xml:lang="en">
<term>Severe Acute Respiratory Syndrome</term>
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<term>Aged</term>
<term>Amino Acid Motifs</term>
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<term>Glycosylation</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Protein Binding</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Young Adult</term>
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<term>Adulte d'âge moyen</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires</term>
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<term>Motifs d'acides aminés</term>
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<front>
<div type="abstract" xml:lang="en">Mannose-binding lectin (MBL) is a serum protein that plays an important role in host defenses as an opsonin and through activation of the complement system. The objective of this study was to assess the interactions between MBL and severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) glycoprotein (SARS-S). MBL was found to selectively bind to retroviral particles pseudotyped with SARS-S. Unlike several other viral envelopes to which MBL can bind, both recombinant and plasma-derived human MBL directly inhibited SARS-S-mediated viral infection. Moreover, the interaction between MBL and SARS-S blocked viral binding to the C-type lectin, DC-SIGN. Mutagenesis indicated that a single N-linked glycosylation site, N330, was critical for the specific interactions between MBL and SARS-S. Despite the proximity of N330 to the receptor-binding motif of SARS-S, MBL did not affect interactions with the ACE2 receptor or cathepsin L-mediated activation of SARS-S-driven membrane fusion. Thus, binding of MBL to SARS-S may interfere with other early pre- or postreceptor-binding events necessary for efficient viral entry.</div>
</front>
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<name sortKey="Bertram, Stephanie" sort="Bertram, Stephanie" uniqKey="Bertram S" first="Stephanie" last="Bertram">Stephanie Bertram</name>
<name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name>
<name sortKey="Glowacka, Ilona" sort="Glowacka, Ilona" uniqKey="Glowacka I" first="Ilona" last="Glowacka">Ilona Glowacka</name>
<name sortKey="Lu, Kai" sort="Lu, Kai" uniqKey="Lu K" first="Kai" last="Lu">Kai Lu</name>
<name sortKey="Pfefferle, Susanne" sort="Pfefferle, Susanne" uniqKey="Pfefferle S" first="Susanne" last="Pfefferle">Susanne Pfefferle</name>
<name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name>
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