The bovine papillomavirus replicon.

The bovine papillomavirus genome contains two cis-acting sequences which can serve as signals for replication. At least three virally encoded genes seem to be involved in plasmid replication: E6, E6/7 and E1. Mutations in either the E6 or the E7 open reading frame create plasmids that are maintained at a low copy number per cell. Mutations in the E1 open reading frame are absolutely lethal to replication. Complementation experiments show that these mutations define separate genes. Experiments are described which show that cells harbouring plasmids with mutations in either the E6 or the E7 open reading frame acquire an immunity to high copy-number plasmids. We suggest that either the cell or the virus encodes a repressor. The positive action of E6 and E6/7 modulates the activity of this repressor to allow for the high copy-number state. Though the viral oncogenes are capable of transforming cells separately when they are expressed as part of certain recombinant DNA expression systems, it is clear that, in the context of the entire viral replicon, interactions between the transforming functions and replication functions must exist.