How Current Direct-Acting Antiviral and Novel Cell Culture Systems for HCV are Shaping Therapy and Molecular Diagnosis of Chronic HCV Infection

We have entered a new era of hepatitis C virus (HCV) therapy in which elimination of infection and disease is a real possibility. HCV cell culture models were instrumental for identification of therapeutic targets, testing candidate drugs, and profiling of therapeutic strategies. Here we describe current and novel methods of cell culture systems for HCV that are allowing investigation of HCV life cycle and virus-host interaction required for replication and propagation. The development of protocols to grow infectious virus in culture and generate hepatocyte cell lines from specific individuals hold great promise to investigate the mechanisms exploited by the virus to spread the infection and the host factors critical for HCV replication and propagation, or resistance to infection. Since host factors are presumably conserved and equally interacting with different HCV isolates and genotypes, the development of drugs targeting host factors essential for virus replication holds great promises in further increasing treatment efficacy. Refocusing of therapeutic goals also impacted in vitro diagnosis. The primary goal of anti-HCV therapy is to achieve a sustained virologic response (SVR) defined as " undetectable" HCV RNA genome in the serum or plasma at 12 to 24 weeks following the end of treatment. Use of direct antiviral agents has substantially changed the threshold of the viral load used to define SVR and led to a reassessment, as discussed herein, of result interpretation and requirements of clinically-approved, quantitative molecular assays.