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Hepatitis C virus infection network

par Tafforeau, Lionel ;de Chassey, B;Navratil, V;André, P;Rabourdin-Combe, C;Lotteau, V
Référence 6th international conference on pathways, networks and systems medicine (16-21 june 2008: Chania, Greece)
Publication Non publié, 2008

Communication à un colloque

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Résumé :

-Oral presentation- Replication of Hepatitis C virus (HCV) relies on multiple interactions with host factors but how these interactions determine infection, pathogenesis and sensitivity to treatment remains largely undefined. To provide a comprehensive view of a HCV mediated cellular infection, we present here a proteome-wide mapping of interactions between HCV and human cellular proteins. A total of 314 protein-protein interactions between HCV and human proteins was identified by yeast two-hybrid, and 170 by literature mining. The dataset was integrated into a reconstructed human interactome and topological analysis of this network showed that cellular proteins interacting with HCV are enriched in highly central and interconnected proteins. The global analysis of these proteins based on functional annotation revealed the enrichment of cellular pathways targeted by HCV. A network comprised of proteins associated with frequent clinical disorders of chronically infected patients was constructed by connecting the insulin, Jak/STAT and TGFb pathways with cellular proteins targeted by HCV. CORE protein appeared as a major perturbator of this network. Focal adhesion was also identified as a new function affected by the virus, mainly by NS3 and NS5A proteins.