Objective Hepatitis C poses a global health problem. Hepatitis C virus (HCV) infects over 170 millions individuals worldwide with the majority remaining undiagnosed and untreated. To this day, there is no vaccine and the available treatment, a combination of ribavirin and pegylated α-interferon has a limited efficacy and important side effects. A better understanding of HCV life cycle will unravel target for new potential therapeutics. In recent years, the knowledge concerning hepatitis C virus (HCV) entry inside the cells has improved, suggesting a complex mechanism involving several (co)receptors. All the studies regarding HCV entry have been performed in non polarized cells, however HCV infects primarily hepatocytes that are highly polarized cells with a complex organization. Polarized cells have two separate membrane domain, the apical and basolateral domain, with different functions and molecular composition. Separation of the two domain is achieved by complex and tightly regulated intracellular trafficking. Tight junction proteins, which play an essential role in cell polarization, figure in the different molecules involved in HCV entry. This suggests that cell polarity might be relevant to HCV entry and probably add supplementary constraints on HCV entry. In this project I therefore propose to study the mechanisms of HCV entry in polarized cells. To develop this project, a model of polarized hepatic cells will be established and used to investigate the specific roles of entry factors, the intracellular trafficking of the virus, the role of cytoskeleton in HCV entry and the dependence on signaling to mediate entry. The data generated in this project will shed new light on a complex and tightly regulated process. Importantly, studying entry in polarized hepatocytes should also bridge the gap between in vitro data and HCV infection in patients. This is especially important as HCV so far lacks a suitable animal model. Fields of science natural sciencesbiological sciencesmicrobiologyvirologymedical and health scienceshealth sciencesinfectious diseasesRNA viruseshepatitis Cnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologycell polaritymedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines 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) Topic(s) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Call for proposal FP7-PEOPLE-2009-RG See other projects for this call Funding Scheme MC-IRG - International Re-integration Grants (IRG) Coordinator CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS EU contribution € 100 000,00 Address RUE MICHEL ANGE 3 75794 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Administrative Contact Jean-Benoist Duburcq (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
