INHIBITION OF DUCK HEPATITIS-B VIRUS-REPLICATION BY INTERFERON-GAMMA

Interferons have been evaluated extensively as candidate antiviral age nts in hepadnaviral infection. We examined the effect of recombinant h uman interferon-gamma on duck hepatitis B virus replication in human h epatoma cells (Huh 7) transiently transfected with cloned duck hepatit is B virus DNA. Cells transfected in the presence of interferon-gamma display a dose-dependent reduction in the levels of encapsidated repli cative intermediates in the cytoplasm, as judged by Southern blotting of purified viral core DNA. The effect is observed at inferferon-gamma concentrations that do not affect growth rate or viability of Huh 7 c ells or their transfection efficiency. Northern analysis of duck hepat itis B virus transcripts in transfected cells demonstrated markedly di minished levels of pre- and subgenomic RNA in interferon-gamma-treated cells. Nuclear run-on analysis was performed to determine whether the se transcripts were diminished due to decreased rates of transcription initiation or increased rates of RNA degradation. Levels of transcrip tion initiation were unaffected by interferon-gamma, implying that duc k hepatitis B virus transcripts in interferon-gamma-treated cells are degraded more rapidly than in untreated cells.