In Vitro Transformation by Bovine Papillomavirus

We have studied tumorigenic transformation of mouse tissue culture cells by bovine papillomavirus (BPV) as a model of papillomavirus-induced cell proliferation. When BPV or its 7.9-kb full-length viral DNA genome induces focal transformation of mouse calls, the viral DNA is maintained in the transformed cells as multiple extrachromosomal copies. The transforming capacity was initially localized to a 69% subgenomic fragment of the viral DNA genome. We have further characterized the BPV DNA sequences that can encode the transforming function by generating and analyzing the transforming activity of a series of BPV DNA deletion mutants. The results indicated that two discontinuous segments of the viral DNA are required for transformation. One segment, near the 5' end of the 69% transforming fragment, probably represents a control element of the viral DNA. The second segment, which lies within the 3' end of the 69% fragment, encodes transforming sequences of the viral DNA. A retroviral control element (the long terminal repeat DNA. A retroviral control element (the long terminal repeat DNA of Harvey murine sarcoma virus) will activate the 2.3-kb segment at the 3' end of the 69% fragment to transform the mouse cells.