Morbillivirus glycoprotein expression induces ER stress, alters Ca2+ homeostasis and results in the release of vasostatin.

Détails

Ressource 1Télécharger: BIB_FA5A8E6C8DE0.P001.pdf (2503.90 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_FA5A8E6C8DE0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Morbillivirus glycoprotein expression induces ER stress, alters Ca2+ homeostasis and results in the release of vasostatin.
Périodique
PLoS One
Auteur(s)
Brunner J.M., Plattet P., Doucey M.A., Rosso L., Curie T., Montagner A., Wittek R., Vandelvelde M., Zurbriggen A., Hirling H., Desvergne B.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2012
Volume
7
Numéro
3
Pages
e32803
Langue
anglais
Résumé
Although the pathology of Morbillivirus in the central nervous system (CNS) is well described, the molecular basis of neurodegenerative events still remains poorly understood. As a model to explore Morbillivirus-mediated CNS dysfunctions, we used canine distemper virus (CDV) that we inoculated into two different cell systems: a monkey cell line (Vero) and rat primary hippocampal neurons. Importantly, the recombinant CDV used in these studies not only efficiently infects both cell types but recapitulates the uncommon, non-cytolytic cell-to-cell spread mediated by virulent CDVs in brain of dogs. Here, we demonstrated that both CDV surface glycoproteins (F and H) markedly accumulated in the endoplasmic reticulum (ER). This accumulation triggered an ER stress, characterized by increased expression of the ER resident chaperon calnexin and the proapoptotic transcription factor CHOP/GADD 153. The expression of calreticulin (CRT), another ER resident chaperon critically involved in the response to misfolded proteins and in Ca(2+) homeostasis, was also upregulated. Transient expression of recombinant CDV F and H surface glycoproteins in Vero cells and primary hippocampal neurons further confirmed a correlation between their accumulation in the ER, CRT upregulation, ER stress and disruption of ER Ca(2+) homeostasis. Furthermore, CDV infection induced CRT fragmentation with re-localisation of a CRT amino-terminal fragment, also known as vasostatin, on the surface of infected and neighbouring non-infected cells. Altogether, these results suggest that ER stress, CRT fragmentation and re-localization on the cell surface may contribute to cytotoxic effects and ensuing cell dysfunctions triggered by Morbillivirus, a mechanism that might potentially be relevant for other neurotropic viruses.
Mots-clé
Animals, Calcium/metabolism, Calreticulin/metabolism, Calreticulin/secretion, Cell Membrane/metabolism, Cercopithecus aethiops, Distemper Virus, Canine/genetics, Distemper Virus, Canine/physiology, Endoplasmic Reticulum Stress, Gene Expression, Glycoproteins/genetics, Hippocampus/cytology, Homeostasis, Neurons/metabolism, Neurons/secretion, Peptide Fragments/metabolism, Peptide Fragments/secretion, Protein Transport, Rats, Up-Regulation, Vero Cells, Viral Proteins/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/05/2012 17:20
Dernière modification de la notice
20/08/2019 16:25
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