Grant: Operating Grant

The infection by the hepatitis C virus (HCV) is a growing public health concern since it affects 170 million people worldwide and is responsible for chronic liver diseases, such as cirrhosis and liver cancer. The standard treatment, involving weekly interferon injection concurrently with the oral administration of ribavirin, is not well tolerated and provides low efficacy. This illustrates the urgent need for the development of new antiviral strategies. The viral proteins interact together and form highly organized and complex cell networks which are used by HCV to control the infection. Additionally, as an obligate parasite, HCV proteins recruit cellular machineries during host infection in order to accomplish critical viral processes. Hence, these virus-virus and virus-host interactions represent potential targets for the development of new classes of antivirals. However, HCV biology and its natural pathogenesis largely remain poorly understood. The aim of this proposal is to understand how virus/virus and virus/host interactions control HCV infection. Especially, we will focus our study on the characterization of NS3/4A and NS5A viral proteins self-interactions and will characterize their respective involvements during the different steps of the HCV life cycle. Moreover, we will address how HCV exploits the interaction between NS3/4A and the cellular protein YB-1 recently identified in our group. Finally, we propose to identify new host machineries that associates with several viral components and to study how they are co-opted by HCV for the benefit of the infection.This study will allow to better understand the pathophysiology and the complexity of HCV infection as well as to identify novel therapeutic targets for the treatment of HCV-infected patients. Indeed, the design of a novel drug class that disrupts the above-mentioned interactions may ultimately represent an efficient therapeutic approach.