Tr. Zemlo et al., ROLE OF TRANSCRIPTIONAL REPRESSORS IN TRANSFORMATION BY BOVINE PAPILLOMAVIRUS TYPE-1, Journal of virology, 68(10), 1994, pp. 6787-6793
Transformation of rodent cells by bovine papillomavirus type 1 (BPV-1)
has been shown to require the direct contribution of the viral oncoge
nes encoded by the E5, E6, and E7 translational open reading frames (O
RFs). It is also known that the viral E1 and E2 ORFs contribute indire
ctly to cellular transformation through their transcriptional modulati
on of these viral oncogenes. A mutant BPV-1 disrupted in two of the pr
oteins 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 vi
ral genes that overlap the E2 repressor genes, (ii) the acquisition of
transformation over time in cells harboring the E2 double-repressor m
utant 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 transcription
al repressor. We propose a model by which the combination of E1 and E2
transcriptional repressors functions to modulate the transforming cap
acity of the virus.