Cellular factors are required to activate bovine papillomavirus-1 early gene transcription and to establish viral plasmid persistence but are not required for cellular transformation

Transcription from the major upstream early gene promoter, P89, of bovine papillomavirus (BPV)-1 is detectable in transfected cells lacking viral gene products yet also responds to viral E2 proteins. In contrast to human papillomaviruses (HPVs), the BPV upstream regulatory region (URR) functions as a transcriptional enhancer in epithelial cells and fibroblasts of bovine, murine or human origin. Mutations of Sp1 and/or two novel transcriptional enhancer factor (TEF)-1 sites within the 5′ URR of the intact BPV-1 genome dramatically reduced P89-initiated mRNA levels, leading to decreased BPV-1 plasmid amplification and inefficient formation of transformed cell foci. However, cell lines transformed with wt or mutant BPV-1 genomes contained similar levels of unintegrated BPV-1 DNA, P89 mRNA and E2-dependent transactivation. We conclude that cellular factors necessary for activating viral early gene transcription, establishment of viral plasmid replication and cell immortalization are not required during the maintenance phase of BPV-1 infection.