Infection of Primary Chimpanzee Hepatocytes with Recombinant Hepatitis D Virus Particles: A Surrogate Model for Hepatitis B Virus

The discovery of hepatitis B virus (HBV) four decades ago initiated the progressive increase in knowledge of an important hepatotropic infectious agent that culminated in the design of the first successful recombinant vaccine for a human infectious disease. Despite this medical achievement, HBV infections continue to present a paramount health problem, which stems from the establishment of chronic infections of HBV that can progress to cirrhosis and hepatocellular carcinoma. There are over 350 million chronic carriers worldwide for which no cure exists, requiring the development of new and better treatments for this disease. The mechanisms of HBV replication and assembly have been well-characterized, owing to the advent of molecular biology techniques and the development of infectious HBV clones. However, two major experimental impediments that were recognized from the beginning continue to be obstacles in the illumination of the early steps of HBV infection. The narrow host range of HBV and the absence of cell lines susceptible to infection have hampered studies on the mechanisms of viral entry. More specifically, the cellular receptor for HBV has not been identified. The isolation of the HBV receptor would create a new target for drug interactions, expanding the limited choice of treatments that currently exists. Identifying viral receptors has often required several distinct approaches. At present, the only hepadnaviral infection system that has yielded promising results and may help identify all viral receptor components is the infection of primary duck hepatocytes with duck hepatitis B virus (DHBV) (1 –10 ).