Objectif The Hepathitis C Virus (HCV) infects more than 150 million people worldwide and is the major cause of hepatic cirrhosis and hepatocellular carcinoma. Current available treatment options have limited efficacy and result in effective viral suppression only in about 50% of treated patients. In addition, HCV exhibits an extremely high genetic variability, mainly due to lack of proofreading activity of the viral RNA polymerase and its ability to generate recombinant genomes. Genetic diversity allows the virus to evolve variants capable to escape immune response and drug pressure and hampers the development of effective vaccines. Research of novel specific drugs is hindered by our limited understanding of several key steps of the viral life cycle.To clarify different aspects of HCV RNA biology, we propose the development of two new assays based on detection of fluorescent proteins. Our first objective is to use the reconstitution of a GFP protein to measure native recombination capability of HCV under different infection conditions. This part will clarify the relative importance of several factors in the generation on new recombinant forms. Subsequently, we will deploy a system to visualize genomic RNA and viral Core protein simultaneously in live cells. By fusing different fluorophores to RNA-binding proteins and to the Core, we will be able to measure packaging and copackaging efficiencies of HCV. Lastly, we will trace the pathway of RNA molecules and Core using live imaging. This will help identifying the sites of recombination, dimerization and packaging in the cell.Taken together, the data produced will help clarify several important aspects of the viral replication cycle, and identify possible new targets for antiviral intervention. Moreover, the systems proposed represent novel approaches to the study of RNA biology in HCV, providing the Copenhagen Hepatitis C Program with advanced and competitive know-how in the field of HCV research. Champ scientifique natural sciencesbiological sciencesmicrobiologyvirologymedical and health scienceshealth sciencesinfectious diseasesRNA viruseshepatitis Cnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesgeneticsRNA Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Appel à propositions FP7-PEOPLE-2010-RG Voir d’autres projets de cet appel Régime de financement MC-IRG - International Re-integration Grants (IRG) Coordinateur REGION HOVEDSTADEN Contribution de l’UE € 100 000,00 Adresse KONGENS VAENGE 2 3400 Hillerod Danemark Voir sur la carte Région Danmark Hovedstaden Nordsjælland Type d’activité Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments) Contact administratif Jens Bukh (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
