ENHANCED TRANSCRIPTIONAL ACTIVATION BY E2 PROTEINS FROM THE ONCOGENICHUMAN PAPILLOMAVIRUSES

A systematic comparison of transcriptional activation by papillomaviru s E2 proteins revealed that the E2 proteins from high-risk human papil lomaviruses (human papillomavirus type 16 [HPV-16] and HPV-18) are muc h more active than are the E2 proteins from low-risk HPVs (HPV-6b and HPV-11). Despite the tropism of HPVs for particular epithelial cell ty pes, this difference in transcriptional activation was observed in a n umber of different epithelial and nonepithelial cells. The enhanced ac tivities of the E2 proteins from high-risk HPV's did not result from h igher steady-state levels of protein in vivo, and in vitro DNA-binding assays revealed similar binding properties for these two classes of E 2 proteins. These results demonstrate that the E2 proteins from high-r isk HPVs have an intrinsically enhanced potential to activate transcri ption from promoters with E2-responsive elements. We found that there are also substantial differences between the activation properties of the bovine papillomavirus type 1 E2 protein and those of either of the two classes of HPV E2 proteins, especially with regard to requirement s for particular configurations of E2 binding sites in the target prom oter. Our results indicate that there are at least three distinct func tional classes of E2 proteins and that these classes of E2 proteins ma y perform different roles during the respective viral life cycles.