HCV Molecular Virology and Animal Models

Hepatitis C virus (HCV) infection was once considered a threat to life but is now curable. This miraculous achievement is the result of years of effort to understand basic HCV biology, which led to the development of HCV cell culture systems eventually enabling drug discovery. Initial studies focused on biochemical characterization of viral proteins and dissected their roles in the virus life cycle. Two of the viral proteins, NS3-4A protease and NS5B polymerase, were selected early on as potential drug targets, and subsequent collaborative efforts of academia and industry led to the development of highly effective inhibitors against these enzymes. Another HCV protein, NS5A that has no known enzymatic activity, was more recently identified as an unexpected target of a highly potent class of anti-HCV inhibitors. Various combinations of these protease, polymerase, and NS5A inhibitors now constitute the current anti-HCV regimens with cure rates of above 95%. This chapter is divided into two parts. The first part begins with a short introduction to HCV and its life cycle and reviews insights into biochemical and functional characteristics of HCV RNA elements and proteins. The second part discusses the HCV animal models and how their use yielded important insights into the viral life cycle, immunity, and disease pathogenesis.