Many different papillomaviruses have low transcriptional activity in spiteof strong epithelial specific enhancers

Transcription of the E6-E7 genes of human papillomavirus type 11 (HPV-11), HPV-16 and HPV-18 is specific to epithelial cells, This mechanism originate s from synergism between different transcription factors such as AP-1, NFI and Sp1, which occur in many different cell types, but whose activity is bi ased in favour of epithelial cells, In this study, the transcriptional regu lation of 14 different papillomavirus types in the absence of the viral E2 transcription factor was compared. Genital HPV types, including high-risk, low-risk and common wart-associated HPVs, were found to have strong epithel ial specific enhancers, irrespective of mucosal or skin target cell and pat hology. Skin specific non-genital HPVs, like HPV-1 and HPV-8, as well as bo vine papillomavirus type 4 (BPV-4), had much lower enhancer activity. Conti guous genomic segments including the enhancer and the E6 promoter of genita l as well as non-genital papillomaviruses generally had very low transcript ional activities, presumably due to silencers between enhancer and promoter sequences. This generalization applies to all cell types tested in spite o f significant quantitative differences between the cervical carcinoma-deriv ed cell line HeLa, the skin-derived cell line HaCat, undifferentiated and d ifferentiated primary keratinocytes, The only enhancer with activity in fib roblasts was identified in BPV-1, apparently a reflection of the broader ta rget cell specificity of this virus. The low transcriptional activity of pa pillomaviruses most likely reflects the low gene expression required during most or even all parts of the life-cycle of these viruses.