The BPV1-E2 trans-acting protein can be either an activator or a repressor of the HPV18 regulatory region

Abstract

The human papillomavirus 18 (HPV 18) long control region contains promoter and enhancer elements whose activity is restricted to several human cell lines of epithelial origin. This enhancer possesses a considerable constitutive activity which is further stimulated in the presence of the E2 trans-activating protein of bovine papillomavirus 1 (BPV1). Surprisingly the same BPV1 protein strongly repressed transcription from the genuine HPV18 enhancer-promoter DNA sequences. We suggest that binding of several molecules of E2 protein between the viral CAAT and TATA elements sterically hinders transcription initiation from this promoter, while the same DNA--protein assembly stimulates the SV40 promoter when cloned in an enhancer configuration upstream of this heterologous promoter. Unlike BPV1-E2 the homologous E2 gene product does not seem to strongly modulate viral transcription. Finally the BPV1-E2 gene product may repress some essential viral or host genes, since we failed to isolate HeLa cells expressing BPV1-E2.