Post date: Jan 18, 2018 4:36:37 PM
Voici une offre de Post-Doc de 2 ans à l’Institut Pasteur de Lille, ayant pour sujet : «Identification and characterization of host factors specifically involved in HCV genotype-3 infection »
Contact: Dr Jean DUBUISSON, jean.dubuisson@ibl.cnrs.fr, tél +33 320 87 11 60
Molecular & Cellular Virology Team (www.ciil.fr)
Center for Infection & Immunity (Inserm, CNRS, University of Lille)
Institut Pasteur de Lille
1 rue du Professeur Calmette, Bât IBL,
59021 Lille Cédex, France
DURATION: 2 YEARS
STARTING DATE: May or June 2018
FINANCIAL SUPPORT: ANRS
Project summary: Identification and characterization of host factors specifically involved in HCV genotype-3 infection
Hepatitis C virus (HCV) is an important human pathogen that infects the liver and establishes chronic infection in the majority of cases, leading to cirrhosis and hepatocellular carcinoma over the course of many years. HCV includes 7 recognized genotypes with genotype-3 being the second most common genotype overall. As compared to other genotypes, genotype 3 is associated with faster progression of fibrosis, a greater risk for hepatocellular carcinoma (HCC), and a higher mortality. Furthermore, higher rates of hepatic steatosis are observed in HCV genotype-3 patients, even in the absence of other metabolic complications, supporting the hypothesis that some specific viral sequences are involved in the etiology of steatosis in genotype-3 patients. As liver damage may be multifactorial, the major challenge in clinical research studies is to carefully exclude patients with risk factors for liver steatosis other than HCV (i.e., patients with obesity, significant alcohol intake, diabetes, ongoing intravenous drug addiction, or use of steatogenic drugs). Cell culture systems are therefore needed to specifically investigate the interactions between HCV genotype-3 and lipid metabolism. The main objective of this proposal is therefore to characterize the interplay between HCV genotype 3 and host cells to better understand the specific interactions between HCV genotype-3 and lipid metabolism. To achieve this goal, we will use a functional genomic screen using a dedicated phenotypic assay relying on the monitoring of HCV genotype-3 infection by high content confocal imaging and apply it to the screening of a genome-wide siRNA library. This will lead to the identification of host cell factors involved in the HCV genotype-3 life cycle. After validation of metabolic host factors involved in HCV genotype-3 replication with a secondary screen, we will identify host factors specifically used by genotype-3 by comparison with other HCV genotypes. Finally, we will use state-of-the-art approaches based on live cell imaging and super-resolution microscopy as well as pharmacological, biochemical and molecular biology tools to decipher the mechanisms of action of the most interesting host factors involved in genotype-3 interplay with lipid metabolism. The characterization of the mechanism of action of these host factors will shed light on the specific interplay between HCV genotype-3 and its host, which will also lead at the longer term to a better understanding of genotype-3 induced pathogenesis.