Development and exploitation of a more true-to-life novel infectious cell culture system for Hepatitis C (HCV) growth for the characterization of new anti-HCV drugs
Hellenic Pasteur Institute
HCV often leads to liver cirrhosis and cancer. Current therapeutic approach (pegylated interferon-α/ribavirin) is effective in only 50% of patients (250 million people worldwide). New therapies are first tested in vitro, in cultured HCV-infected hepatocytes, to verify their efficacy against viral replication and their cytotoxic action. These studies are being performed under atmospheric oxygen levels (20% v/v). However, in the liver, oxygen tensions range between 12 and 1% with a median value of 3% (v/v). Investigating HCV proliferation in human hepatoma cell lines cultured at 3% or 20% oxygen revealed that viral replication is highly enhanced at 3%. Moreover, 3% oxygen favors metabolic activity of both healthy and HCV-infected cells. To further examine this phenomenon, the team proposes to use primary human hepatocytes and different HCV strains, explore changes in hepatocellular transcript expression profile caused at 3% oxygen and sought specific cellular factors important for HCV replication by gene silencing.
Final Report (in Greek)
Niki Vassilaki, Researcher, Molecular Virology Laboratory, Hellenic Pasteur Institute
Ioannis Koskinas, Assistant Professor in Pathology-Hepatology, Second Pathological Clinic, Faculty of Medicine, National and Kapodistrian University of Athens (EKPA), Ippokrateio General Hospital of Athens
Pinelopi Mavromara, Professor in Microbiology, Department of Molecular Biology and Genetics, Democritus University of Thrace