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Title

HSV-1 Cgal+ infection promotes quaking RNA binding protein production and induces nuclear-cytoplasmic shuttling of quaking I-5 isoform in human hepatoma cells

Authors
Sánchez-Quiles, Virginia
Mora, María I
Segura, Victor
Greco, Anna
Epstein, Alberto L
Foschini, Maria Giovanna
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Published in Molecular and Cellular Proteomics. 2011, vol. 10, no. 6, p. M111.009126
Abstract 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.
Keywords AlgorithmsCell Adhesion Molecules/metabolismCell Line, TumorCell Nucleus/metabolism/virologyCyclin-Dependent Kinase Inhibitor p27/metabolismCyclin-Dependent Kinase Inhibitor p57/metabolismCytoplasm/metabolismHerpes Simplex/metabolism/virologyHerpesvirus 1, Human/genetics/growth & development/physiologyHumansProtein Isoforms/genetics/metabolismProtein TransportRNA InterferenceRNA-Binding Proteins/genetics/metabolismStatistics, NonparametricTandem Mass SpectrometryTwo-Dimensional Difference Gel ElectrophoresisViral Plaque AssayViral Proteins/metabolism
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PMID: 21467216
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Research group Groupe de Protéomique biomédicale (635)
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SÁNCHEZ-QUILES, Virginia et al. HSV-1 Cgal+ infection promotes quaking RNA binding protein production and induces nuclear-cytoplasmic shuttling of quaking I-5 isoform in human hepatoma cells. In: Molecular and Cellular Proteomics, 2011, vol. 10, n° 6, p. M111.009126. https://archive-ouverte.unige.ch/unige:25567

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Deposited on : 2013-01-16

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