Molecular Systems Biology · 2008 · 384 citations · 59 references
Life SciencesInfectious DiseasesMolecular BiologyMolecular VirologyProteomicsVirologyHost-virus InteractionsMolecular Interaction NetworksProtein Interaction DomainsProtein Interaction MappingProtein-protein Interaction NetworksViral HepatitisEssential Functions IdentificationFunctional AnnotationHost Factors In InfectionHuman Interactome MappingInteractomicsProtein-protein Interaction DomainsProtein-protein Interaction MappingVirus-host Protein Interactions
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 TGFbeta 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.
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