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Hepatitis C virus infection protein network
Authors:A Aublin‐Gex  G Meiffren  F Pradezynski  B F Faria  T Chantier  M Le Breton  J Pellet  N Davoust  P E Mangeot  A Chaboud  F Penin  Y Jacob  P O Vidalain  M Vidal  P André  C Rabourdin‐Combe  V Lotteau
Affiliation:1. IMAP Team, Inserm Unit 851, Lyon, France;2. IFR128 BioSciences Lyon‐Gerland, Université de Lyon, Lyon, France;3. Institut de Biologie et Chimie des Protéines, CNRS UMR 5086, Lyon, France;4. Unité Postulante de Génétique, Papillomavirus et Cancer Humain, Institut Pasteur, Paris, France;5. Laboratoire de Génomique Virale et Vaccination, Institut Pasteur, CNRS URA 3015, Paris, France;6. Center for Cancer Systems Biology, Dana‐Farber Cancer Institute, Harvard Medical School, Boston, MA, USA;7. Hospices Civils de Lyon, H?pital de la Croix‐Rousse, Laboratoire de virologie, Lyon, France
Abstract:
A proteome‐wide mapping of interactions between hepatitis C virus (HCV) and human proteins was performed to provide a comprehensive view of the cellular infection. A total of 314 protein–protein interactions between HCV and human proteins was identified by yeast two‐hybrid and 170 by literature mining. Integration of this data set into a reconstructed human interactome showed that cellular proteins interacting with HCV are enriched in highly central and interconnected proteins. A global analysis on the basis of functional annotation highlighted the enrichment of cellular pathways targeted by HCV. A network of proteins associated with frequent clinical disorders of chronically infected patients was constructed by connecting the insulin, Jak/STAT and TGFβ pathways with cellular proteins targeted by HCV. CORE protein appeared as a major perturbator of this network. Focal adhesion was identified as a new function affected by HCV, mainly by NS3 and NS5A proteins.
Keywords:functional analysis  hepatitis C  interactome  virus‐host cell
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