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Human hepatitis delta virus has a single-stranded circular RNA genome that replicates by RNA-directed RNA synthesis. The virus encodes only a single protein, the delta antigen, which both is small (22 kDa) and lacks sequence homology to known RNA polymerases, suggesting that the virus employs a cellular polymerase for replication. Consistent with this suggestion, we have used homogenized nuclei from a human hepatoma cell line, HepG2, to demonstrate RNA-directed RNA synthesis from both genomic hepatitis delta virus RNA and its complement, the antigenomic RNA. RNA polymerase II was responsible for this transcription because the reaction was inhibited both by low doses of alpha-amanitin and by a monoclonal antibody specific for polymerase II. In addition, it was found that the majority of the RNA products were processed, presumably by self-cleavage and self-ligation, to produce covalently closed circular molecules.

The RNAs of hepatitis delta virus are copied by RNA polymerase II in nuclear homogenates