| Domaine : |
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Sciences du Vivant/Biochimie, Biologie Moléculaire
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| Titre : |
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HSV-1 Cgal+ infection promotes quaking RNA binding protein production and induces nuclear-cytoplasmic shuttling of quaking I-5 isoform in human hepatoma cells. |
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| Auteur(s) : |
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Virginia Sánchez-Quiles1, María I Mora1, 2, Victor Segura1, Anna Greco3, Alberto L Epstein3, Maria Giovanna Foschini, Loïc Dayon4, Jean-Charles Sanchez4, Jesús Prieto5, 6, Fernando J Corrales1, Enrique Santamaría1 |
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| Laboratoire : |
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| Résumé : |
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Herpesvirus type 1 (HSV-1) based oncolytic vectors arise as a promising therapeutic alternative for neoplastic diseases including hepatocellular carcinoma. However, the mechanisms mediating the host cell response to such treatments are not completely known. It is well established that HSV-1 infection induces functional and structural alterations in the nucleus of the host cell. In the present work, we have used gel-based and shotgun proteomic strategies to elucidate the signaling pathways impaired in the nucleus of human hepatoma cells (Huh7) upon HSV-1 Cgal(+) infection. Both approaches allowed the identification of differential proteins suggesting impairment of cell functions involved in many aspects of host-virus interaction such as transcription regulation, mRNA processing, and mRNA splicing. Based on our proteomic data and additional functional studies, cellular protein quaking content (QKI) increases 4 hours postinfection (hpi), when viral immediate-early genes such as ICP4 and ICP27 could be also detected. Depletion of QKI expression by small interfering RNA results in reduction of viral immediate-early protein levels, subsequent decrease in early and late viral protein content, and a reduction in the viral yield indicating that QKI directly interferes with viral replication. In particular, HSV-1 Cgal(+) induces a transient increase in quaking I-5 isoform (QKI-5) levels, in parallel with an enhancement of p27(Kip1) protein content. Moreover, immunofluorescence microscopy showed an early nuclear redistribution of QKI-5, shuttling from the nucleus to the cytosol and colocalizing with nectin-1 in cell to cell contact regions at 16-24 hpi. This evidence sheds new light on mechanisms mediating hepatoma cell response to HSV-1 vectors highlighting QKI as a central molecular mediator. |
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Langue du texte
intégral : |
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Anglais |
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| Journal : |
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Mol Cell Proteomics |
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| Audience : |
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internationale |
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| Type de publication : |
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Articles dans des revues avec comité de lecture |
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| Date de publication : |
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06/2011 |
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Date de publication
électronique : |
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05/04/2011 |
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| Volume : |
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10 |
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| Numéro : |
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6 |
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| Page, identifiant, ... : |
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M111.009126 |
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| Descripteur(s) MeSH : |
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Algorithms – Cell Adhesion Molecules – Cell Line – Tumor – Cell Nucleus – Cyclin-Dependent Kinase Inhibitor p27 – Cyclin-Dependent Kinase Inhibitor p57 – Cytoplasm – Herpes Simplex – Herpesvirus 1 – Human – Humans – Protein Isoforms – Protein Transport – RNA Interference – RNA-Binding Proteins – Statistics – Nonparametric – Tandem Mass Spectrometry – Two-Dimensional Difference Gel Electrophoresis – Viral Plaque Assay – Viral Proteins |
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