Integrated defective replication units of hepatitis B virus.

Stable transformants of the human hepatoma cell line HepG2 were established that constitutively transcribe a DNA unit consisting of a stretch of hepatitis B virus DNA and of nonviral DNA conferring resistance to neomycin. Previously it had been shown that upon cotransfection of such transformants with replication-competent HBV DNA, transcripts of such units become reverse transcribed, demonstrating that DNA constructs can function as defective replication units. Transformed cell lines stably transcribing the defective replication units could be shown to use the transcriptional starts for the viral pregenome and for the large core antigen at a ratio of 9:1. Upon the induction of replicative processes in the transformed cells by transfection with replication-competent wild type (wt) DNA, defective pregenomes transcribed from the integrated state became included in the pool of replicating nucleic acids.