Role of transcriptional repressors in transformation by bovine papillomavirus type 1.

Transformation of rodent cells by bovine papillomavirus type 1 (BPV-1) has been shown to require the direct contribution of the viral oncogenes encoded by the E5, E6, and E7 translational open reading frames (ORFs). It is also known that the viral E1 and E2 ORFs contribute indirectly to cellular transformation through their transcriptional modulation of these viral oncogenes. A mutant BPV-1 disrupted in two of the proteins encoded by the E2 ORF, the E2 transcriptional repressors, has a complex transformation phenotype. In this paper, we provide evidence that (i) this phenotype is not attributable to the absence of other viral genes that overlap the E2 repressor genes, (ii) the acquisition of transformation over time in cells harboring the E2 double-repressor mutant correlates with reversions of the mutations that disrupt one of the E2 repressor genes, E8/E2TR, and (iii) the initial transformation defect in the E2 double-repressor mutant can be rescued by disruption of the full-length protein encoded by the E1 ORF, the E1 transcriptional repressor. We propose a model by which the combination of E1 and E2 transcriptional repressors functions to modulate the transforming capacity of the virus.