Development of an Adenovirus Vector Containing a Hepatitis C Virus Expression Cassette and Its Application

Abstract

  Hepatitis C virus (HCV) is a hepatotropic member of the Flaviviridae family and contains a 9.6 kb positive-sense RNA genome. Approximately 170-million people are infected with HCV worldwide. These people face increased risks of chronic hepatitis, cirrhosis and hepatocellular carcinoma compared with the general population. Transduction of the HCV genome into hepatocytes is essential for understanding the mode of action of HCV infection, and for preparing HCV, evaluating HCV replication, and screening anti-HCV drugs. Although electroporation of in vitro-synthesized HCV genome and transduction of plasmid vectors containing the HCV genome are widely used in HCV research, a more convenient system with higher transduction efficiency is needed. Among viral transduction systems, adenovirus (Ad) vector is one of the most efficient and convenient systems; Ad vector has been widely used in clinical gene therapies. Therefore, Ad vector is a promising system for the delivery of the HCV genome; however, an Ad vector expressing the HCV genome has never been developed. We here describe the preparation of an Ad vector expressing the HCV genome, and outline future directions of HCV research using this vector system.