Co-transcribed 3' host sequences augment expression of integrated hepatitis B virus DNA.

We have previously reported the cloning and structural analysis of integrated hepatitis B virus DNA copies from the human hepatoma cell line PLC/PRF/5. Here we show that the cloned DNA fragments of 10.7 kb and 10.5 kb contain intact coding sequences for HBsAg since Ltk- cells transfected with these DNAs secrete considerable amounts of HBsAg. We show for the 10.7-kb fragment that multiple readthrough messages composed of viral as well as cellular sequences are transcribed. These RNAs differ only in their 3' sequences. Furthermore, the 10.7-kb insert leads to a substantial increase in HBsAg produced compared with HBV DNA and with the 10.5-kb insert. We provide evidence that the different 3' sequences on the HBsAg transcripts account for the augmentation of expression.