ABSTRACT
This chapter elaborates the discovery of the HBV-like viruses, woodchuck hepatitis virus (WHV), ground squirrel hepatitis virus (GSHV), and duck hepatitis B virus (DHBV), energized a rapid investigation of the hepadnavirus replication cycle. Based on the structural analyses of virion DNA purified from serum and on replicative intermediates present in infected livers, the following model for hepadnavirus replication was proposed. On infection, relaxed circular virion DNA is converted into covalently closed circular DNA (cccDNA). cccDNA directs the synthesis of viral mRNAs and the synthesis of the template for reverse transcription, termed pregenomic RNA. Pregenomic RNA is packaged into core particles and subsequently copied into minus-strand DNA, followed by plus-strand DNA synthesis. The final product of this reaction is relaxed circular virion DNA. cccDNA accumulates in the nucleus of infected cells. The ability to transfect tissue culture cells with cloned DNA was exploited early on as a means of expressing the HBV genome in cell culture.
