The coronavirus spike protein induces endoplasmic reticulum stress and upregulation of intracellular chemokine mRNA concentrations.
Identifieur interne : 001A31 ( Ncbi/Checkpoint ); précédent : 001A30; suivant : 001A32The 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 ; Peter J. Bredenbeek ; Willy J M. SpaanSource :
- 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.
- Animaux, Glycoprotéine de spicule des coronavirus, Lignée cellulaire, Régulation positive, Souris.
English descriptors
- KwdEn :
- Animals, Cell Line, Chemokine CXCL2 (genetics), Chemokines (genetics), Endoplasmic Reticulum (pathology), Endoplasmic Reticulum (virology), Membrane Glycoproteins (physiology), Mice, Murine hepatitis virus (pathogenicity), RNA, Messenger (analysis), SARS Virus (pathogenicity), Spike Glycoprotein, Coronavirus, Up-Regulation, Viral Envelope Proteins (physiology).
- 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.
DOI: 10.1128/JVI.01033-07
PubMed: 17670839
Affiliations:
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pubmed:17670839Le document en format XML
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<affiliation wicri:level="1"><nlm:affiliation>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, LUMC E4-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands.</nlm:affiliation>
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<term>Chemokines (genetics)</term>
<term>Endoplasmic Reticulum (pathology)</term>
<term>Endoplasmic Reticulum (virology)</term>
<term>Membrane Glycoproteins (physiology)</term>
<term>Mice</term>
<term>Murine hepatitis virus (pathogenicity)</term>
<term>RNA, Messenger (analysis)</term>
<term>SARS Virus (pathogenicity)</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Up-Regulation</term>
<term>Viral Envelope Proteins (physiology)</term>
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<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>
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<term>Réticulum endoplasmique (virologie)</term>
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<term>Virus du SRAS (pathogénicité)</term>
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<term>Mice</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Up-Regulation</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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