In vivo study of the mechanism of action of antiviral agents against hepadna virus replication in the liver. Resistance of supercoiled viral DNA.

The mode of action of antiviral agents (interferon and adenine arabinoside) was studied in human and in animals chronically infected with hepadna virus. Interferon (36-100 megaunits) was given to 20 carrier patients, and hepatitis B virus (HBV)-DNA replicative forms were studied in pre- and post-treatment biopsies. ARA-A was given intravenously to duck hepatitis B virus (DHBV)-infected ducks. Changes in intrahepatic viral replicative forms were studied by Southern blotting using 32P-labelled HBV or DHBV probe. Our study indicates that both interferon and ARA-A seem to effectively decrease 'mature' forms of viral DNA by an effect on either mRNA or DNA polymerase. However, the supercoiled viral DNA tends to resist the treatment, and may become the transcribing template for a new cycle of viral replication after cessation of the drugs.