The Use of Hepatocytes to Investigate HDV Infection: The HDV/HepaRG Model

Worldwide, it is estimated that more than 350 million people are chronically infected with hepatitis B virus (HBV), approximately 15 million of whom are coinfected with hepatitis D virus (HDV), a satellite of HBV that uses the envelope proteins of the latter to assemble its infectious particles. For a long time after HBV discovery, research on the viral life cycle, viral entry in particular, has been hampered by the lack of practical tissue culture systems. To date, in vitro isolation and serial propagation of HBV are still problematic, but the examination of the entire HBV life cycle is possible using two separate systems: (i) permissive human hepatoma cell lines to study HBV DNA replication, viral transcription, translation, assembly, and release of viral particles and (ii) primary cultures of human or chimpanzee hepatocytes or the susceptible HepaRG cell line for viral entry examination. The experimental model described here for analyzing the function of HBV envelope proteins at viral entry is based on this dual tissue culture system, in which HDV is substituted to HBV for practical reasons.