Abstract
Bovine papillomavirus type 1 (BPV-1) is capable of replicating as a stable, high-copy-number plasmid in transformed rodent cells. The BPV-1 E1 open reading frame (ORF) encodes multiple functions involved in viral DNA replication. Mutations which disrupt the translational integrity of the E1 ORF disable the viral genome from replicating as a stable plasmid and result in the integration of the viral genome into the host chromosome generally at a low copy number. Despite the low copy number of the integrated genomes, BPV-1 E1 mutants transform rodent cells to anchorage independence very efficiently, at levels equal to or greater than that of wild-type (wt) BPV-1. Studies were performed to provide insight into why these low-copy-number, replication-defective mutants are capable of expressing an equal or greater transformation potential than wt BPV-1. Analysis of viral RNA revealed higher rates of transcription per viral genome in cells harboring E1 mutated BPV-1 DNA than in cells containing wt BPV-1 DNA. Furthermore, the levels of viral RNA mapping the P89 promoter were found to be 15- to 35-fold higher in cells transformed by E1 mutated DNAs compared with wt BPV-1 transformants. This promoter controls expression of the BPV-1 E6 transforming gene and is regulated by the viral E2 gene products. The studies presented in this report determined that the E1 mutants were perturbed in their E2 transcriptional regulation, suggesting a possible explanation for the observed P89 induction. Mutations throughout the E1 ORF, in either of the two regions previously identified as encoding distinct replication functions, were altered in viral transcription.
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Selected References
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