The arrangement of integrated viral DNA is different in BK virus-transformed mouse and hamster cells

Secondary mouse and hamster cells were transformed with BK virus (BKV) or with purified BKV DNA. Restriction analysis of viral sequences present in transformed cell lines yielded complex patterns, indicating the presence in most lines of more than one viral intergration/cell and the existence of a large number of available integration sites. In spite of this variability, however, the arrangement of integrated viral sequences had specific features in the two types of transformed cells. Tandem insertions of full-size BKV genomes, which were a constant feature of transformed mouse lines, were not found in hamster lines. These appeared to contain no complete, intact BKV genomes, but only genomes interrupted by the insertion event or tandem integrations of incomplete viral sequences. Traces of free, full-size viral DNA were observed in all transformed mouse lines, but not in hamster lines. One transformed hamster line, after 84 passages in culture, showed the presence of tandemly integrated, full-size BKV DNA, which was not found in cells at 14 passages after the appearance of the transformed phenotype. This was the only BKV transformed line from which virus could be rescued by fusion with permissive cells. These results suggest that BKV DNA integration occurs differently in hamster (nonpermissive) and mouse (semipermissive) cells, and support the idea that excision of integrated viral DNA occurs usually via homologous recombination.