Repression of bovine papillomavirus type 1 transcription by the E1 replication protein

Bovine papillomavirus type 1 (BPV-1) is the prototype virus for the study of papillomavirus gene regulation. The functions of the BPV-1 E2 proteins in transcriptional regulation have been well characterized. The BPV-1 E1 protein is required for viral DNA replication and can bind to the origin of replication alone or in a complex with the E2 transactivator protein. In this study, we demonstrated that the BPV-1 E1 protein is also involved in transcriptional regulation. The E1 protein significantly repressed E2-transactivated transcription from the major early promoter P89. This activity is consistent with the elevated level of P89 transcription observed in BPV-1 E1 open reading frame mutants. Transcriptional repression by E1 correlated with the ability of an E1-E2 protein complex to bind the replication origin but was not dependent on viral DNA replication. These studies identify a new mechanism involved in the regulation of papillomavirus transcription which has implications regarding expression of the viral transforming functions.