Chronic hepatitis C virus (HCV) infection is a slow and asymptomatic progressive liver disease leading to steatosis, an abnormal accumulation of lipid droplets (LDs) in hepatocytes, as well as long-term complications such as cirrhosis and hepatocellular carcinoma (HCC). In line with HCV extensive genetic diversity, including 8 genotypes and >90 subtypes, clinical studies have reported an association between HCV genotype 3 chronic infections and a higher prevalence of steatosis and increased fibrosis progression rate toward cirrhosis and HCC. Among viral factors, HCV core protein appears to have a key role in the dysregulation of hepatocyte signaling and metabolic pathways representing important risk factors for steatosis and HCC. However, whether Core genotypic origin differentially modulates key biological pathways that may account for aggravated clinical outcomes remains an open question. Therefore, our research project aims at identifying genotype-specific mechanisms and viral determinants involved in host pathogenic responses, using novel viral models encoding core proteins of different genotypes.
Following a first high-throughput screen performed at the Biomics platform, we have previously identified differential modulation of key pro-steatogenic and pro-oncogenic factors in link with core genotypic origin. To consolidate these promising results, we wish to perform a second screen based on an additional set of intergenotypic viruses encoding core from other genotypes and strains with distinct clinical features.
