Integrated structures of HBV DNA in chronic hepatitis and hepatoma tissues

Cellular DNAs of chronically hepatitis B virus (HBV)-infected human livers were analysed by Southern blot hybridization for the presence of integrated HBV DNA. In 15 out of 16 tissue samples, random HBV DNA integration was evident. By molecular cloning and structural analyses of 19 integrants from 3 chronic hepatitis tissues, rearrangement of HBV DNA with inverted duplication or translocation of cellular flanking DNA at the virus-cell junction was noted. Thus, the rearrangement of HBV DNA or cellular flanking DNA not to be a specific incident of HCC formation. Analyses of various integrants bearing HBV DNA rearrangement and their cellular counterpart DNAs failed to indicate any gross structural alteration in cellular DNA except for a small deletion at the integration sites, indicating HBV DNA rearrangement with inverted duplication to possibly occur prior to integration. Based on nucleotide sequencing analyses of virus-virus junctions, a mechanism of this inverted duplication of HBV DNA is proposed, in which an illegitimate recombination may take place by means of a patchy homology on one side of adjoining viral sequences.