The papillomaviruses are a group of small DNA viruses associated with benign and malignant proliferative lesions in a variety of higher vertebrates. Currently, there are recognized to be 46 distinct human papillomaviruses (HPVs) and six bovine papillomaviruses (BPVs). The lytic expression of these viruses is linked to the state of differentiation of squamous epithelial cells and to date no tissue culture system exists for their propagation in the laboratory. The bovine papillomavirus type 1 (BPV-1) is one of a subgroup of papillomaviruses which is capable of inducing fibroblastic tumors when inoculated into hamsters and is capable of inducing morphologic transformation of certain rodent cells in tissue culture. To date, transformation of rodent cells remains the only in vitro assay for the systematic study of the papillomaviruses. Because of this property, BPV-1 has become the prototype for unravelling the molecular biology of the papillomaviruses. A unique feature of this papillomavirus transformation system is that the viral DNA does not integrate into the host chromosome. The DNA remains extrachromosomal as a stable multiple copy plasmid. The factors involved in stable transformtaion, as well as for stable plasmid maintenance, are being extensively studies. A second characteristic associated with the papillomavirus infection is the propensity of certain viruses to be associated with lesions which may progress to carcinomas. What factors, either viral or host, which are involved in such a progression from a benign lesions to a carcinoma are as yet unknown. Our studies are designed to unravel the molecular biology of the normal virus infection of cells as well as for understanding the viral and cellular factors involved in carcinogenic progression. We have determined that BPV-1 encodes at least two genes which can independently transform mouse cells. Also, we have mapped transcriptional regulatory elements in the LCR of BPV-1 which are trans-activated by the full viral E2 gene product. A transcriptional repressor is encoded by the 3' portion of the E2 ORF. This domain of E2 contains the DNA binding site.
