Construction of Recombinant Adenoviruses that Produce Infectious Hepatitis B Virus

Hepatitis B viruses (HBVs) are characterized by their high species and tissue specificity. Because of the large number of patients chronically infected with HBV, the development of new treatment strategies remains a major goal but is hindered by the lack of infection systems that would allow testing. Only primary human or humanoid hepatocytes are fully permissive for HBV infection. Consequently, no permissive cell line and no convenient small animal model are available to study HBV infection. However, highly differentiated liver cell lines support virus replication following transfection of replication competent HBV constructs. Stable cell lines with integrated HBV genomes, for example, HepG 2.2.15 cells (1 ), are commonly used for assessing the action of drugs on HBV replication. HBV-transgenic mice (2 ) and have been generated and were proven to be very useful for immunological studies. However, stable cell lines as well as transgenic mice, unlike in natural infection, replicate HBV from an integrated genome that cannot be eliminated. In addition, they cannot mimic an acute infection and the level of virus replication cannot be varied or adjusted.