The coronavirus spike protein induces endoplasmic reticulum stress and upregulation of intracellular chemokine mRNA concentrations
Identifieur interne : 003B17 ( Main/Exploration ); précédent : 003B16; suivant : 003B18The coronavirus spike protein induces endoplasmic reticulum stress and upregulation of intracellular chemokine mRNA concentrations
Auteurs : Gijs A. Versteeg [Pays-Bas] ; Paula S. Van De Nes [Pays-Bas] ; Peter J. Bredenbeek [Pays-Bas] ; Willy J. M. Spaan [Pays-Bas]Source :
- Journal of virology [ 0022-538X ] ; 2007.
Descripteurs français
- KwdFr :
- ARN messager (analyse), Animaux, Chimiokine CXCL2 (génétique), Chimiokines (génétique), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (physiologie), Lignée cellulaire, Protéines de l'enveloppe virale (physiologie), Régulation positive, Réticulum endoplasmique (anatomopathologie), Réticulum endoplasmique (virologie), Souris, Virus de l'hépatite murine (pathogénicité), Virus du SRAS (pathogénicité).
- MESH :
- analyse : ARN messager.
- anatomopathologie : Réticulum endoplasmique.
- génétique : Chimiokine CXCL2, Chimiokines.
- pathogénicité : Virus de l'hépatite murine, Virus du SRAS.
- physiologie : Glycoprotéines membranaires, Protéines de l'enveloppe virale.
- virologie : Réticulum endoplasmique.
- Pascal (Inist)
English descriptors
- KwdEn :
- Animals, Cell Line, Chemokine, Chemokine CXCL2 (genetics), Chemokines (genetics), Coronavirus, Endoplasmic Reticulum (pathology), Endoplasmic Reticulum (virology), Endoplasmic reticulum, Intracellular, Membrane Glycoproteins (physiology), Messenger RNA, Mice, Murine hepatitis virus (pathogenicity), Protein, RNA, Messenger (analysis), SARS Virus (pathogenicity), Spike Glycoprotein, Coronavirus, Stress, Up-Regulation, Viral Envelope Proteins (physiology), Virology.
- MESH :
- chemical , analysis : RNA, Messenger.
- chemical , genetics : Chemokine CXCL2, Chemokines.
- pathogenicity : Murine hepatitis virus, SARS Virus.
- pathology : Endoplasmic Reticulum.
- chemical , physiology : Membrane Glycoproteins, Viral Envelope Proteins.
- virology : Endoplasmic Reticulum.
- Animals, Cell Line, Mice, Spike Glycoprotein, Coronavirus, Up-Regulation.
Abstract
Murine hepatitis virus (MHV) and severe acute respiratory syndrome (SARS) coronavirus (CoV) are two of the best-studied representatives of the family Coronaviridae. During CoV infection, numerous cytokines and chemokines are induced in vitro and in vivo. Human interleukin 8 and its mouse functional counterpart, CXCL2, are early-expressed chemokines. Here we show that SARS-CoV and MHV induce endoplasmic reticulum (ER) stress and Cxcl2 mRNA transcription during infection in vitro. Expression of the viral spike protein significantly induced ER stress and Cxcl2 mRNA upregulation, while expression of the other structural genes did not. Additional experiments with UV-inactivated virus, cell-cell fusion-blocking antibodies, and an MHV mutant with a defect in spike protein maturation demonstrated that spike-host interactions in the ER are responsible for the induction of ER stress and subsequent Cxcl2 mRNA transcription. Despite significant increases in levels of Cxcl2 mRNA and functional nucleus-to-cytoplasm RNA transport, no CXCL2 protein was released into the medium from MHV-infected cells. Yet Sendai virus-infected cells showed substantial Cxcl2 mRNA induction and a simultaneous increase in levels of secreted CXCL2 protein. Our results demonstrate that expression of CoV spike proteins induces ER stress, which could subsequently trigger innate immune responses. However, at that point in infection, translation of host mRNA is already severely reduced in infected cells, preventing the synthesis of CXCL2 and ER stress proteins despite their increased mRNA concentrations.
Affiliations:
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Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">The coronavirus spike protein induces endoplasmic reticulum stress and upregulation of intracellular chemokine mRNA concentrations</title>
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<series><title level="j" type="main">Journal of virology</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Cell Line</term>
<term>Chemokine</term>
<term>Chemokine CXCL2 (genetics)</term>
<term>Chemokines (genetics)</term>
<term>Coronavirus</term>
<term>Endoplasmic Reticulum (pathology)</term>
<term>Endoplasmic Reticulum (virology)</term>
<term>Endoplasmic reticulum</term>
<term>Intracellular</term>
<term>Membrane Glycoproteins (physiology)</term>
<term>Messenger RNA</term>
<term>Mice</term>
<term>Murine hepatitis virus (pathogenicity)</term>
<term>Protein</term>
<term>RNA, Messenger (analysis)</term>
<term>SARS Virus (pathogenicity)</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Stress</term>
<term>Up-Regulation</term>
<term>Viral Envelope Proteins (physiology)</term>
<term>Virology</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (analyse)</term>
<term>Animaux</term>
<term>Chimiokine CXCL2 (génétique)</term>
<term>Chimiokines (génétique)</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (physiologie)</term>
<term>Lignée cellulaire</term>
<term>Protéines de l'enveloppe virale (physiologie)</term>
<term>Régulation positive</term>
<term>Réticulum endoplasmique (anatomopathologie)</term>
<term>Réticulum endoplasmique (virologie)</term>
<term>Souris</term>
<term>Virus de l'hépatite murine (pathogénicité)</term>
<term>Virus du SRAS (pathogénicité)</term>
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<keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>RNA, Messenger</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Chemokine CXCL2</term>
<term>Chemokines</term>
</keywords>
<keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>ARN messager</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Réticulum endoplasmique</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Chimiokine CXCL2</term>
<term>Chimiokines</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Murine hepatitis virus</term>
<term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus de l'hépatite murine</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Endoplasmic Reticulum</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Glycoprotéines membranaires</term>
<term>Protéines de l'enveloppe virale</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Membrane Glycoproteins</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Réticulum endoplasmique</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Endoplasmic Reticulum</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cell Line</term>
<term>Mice</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Up-Regulation</term>
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<term>Coronavirus</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Lignée cellulaire</term>
<term>Protéine</term>
<term>Régulation positive</term>
<term>Réticulum endoplasmique</term>
<term>Souris</term>
<term>Stress</term>
<term>Intracellulaire</term>
<term>Chimiokine</term>
<term>RNA messager</term>
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<front><div type="abstract" xml:lang="en">Murine hepatitis virus (MHV) and severe acute respiratory syndrome (SARS) coronavirus (CoV) are two of the best-studied representatives of the family Coronaviridae. During CoV infection, numerous cytokines and chemokines are induced in vitro and in vivo. Human interleukin 8 and its mouse functional counterpart, CXCL2, are early-expressed chemokines. Here we show that SARS-CoV and MHV induce endoplasmic reticulum (ER) stress and Cxcl2 mRNA transcription during infection in vitro. Expression of the viral spike protein significantly induced ER stress and Cxcl2 mRNA upregulation, while expression of the other structural genes did not. Additional experiments with UV-inactivated virus, cell-cell fusion-blocking antibodies, and an MHV mutant with a defect in spike protein maturation demonstrated that spike-host interactions in the ER are responsible for the induction of ER stress and subsequent Cxcl2 mRNA transcription. Despite significant increases in levels of Cxcl2 mRNA and functional nucleus-to-cytoplasm RNA transport, no CXCL2 protein was released into the medium from MHV-infected cells. Yet Sendai virus-infected cells showed substantial Cxcl2 mRNA induction and a simultaneous increase in levels of secreted CXCL2 protein. Our results demonstrate that expression of CoV spike proteins induces ER stress, which could subsequently trigger innate immune responses. However, at that point in infection, translation of host mRNA is already severely reduced in infected cells, preventing the synthesis of CXCL2 and ER stress proteins despite their increased mRNA concentrations.</div>
</front>
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<affiliations><list><country><li>Pays-Bas</li>
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<tree><country name="Pays-Bas"><noRegion><name sortKey="Versteeg, Gijs A" sort="Versteeg, Gijs A" uniqKey="Versteeg G" first="Gijs A." last="Versteeg">Gijs A. Versteeg</name>
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<name sortKey="Bredenbeek, Peter J" sort="Bredenbeek, Peter J" uniqKey="Bredenbeek P" first="Peter J." last="Bredenbeek">Peter J. Bredenbeek</name>
<name sortKey="Spaan, Willy J M" sort="Spaan, Willy J M" uniqKey="Spaan W" first="Willy J. M." last="Spaan">Willy J. M. Spaan</name>
<name sortKey="Van De Nes, Paula S" sort="Van De Nes, Paula S" uniqKey="Van De Nes P" first="Paula S." last="Van De Nes">Paula S. Van De Nes</name>
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