Transcriptional activation of the human papillomavirus type 5 and 16 long control region in cells from cutaneous and mucosal origin

Human papillomavirus type-16 (HPV-16) infects mucosal epithelium and is the most common type found in cervical cancer. HPV-5 infects cornified epithelium and is the most common type found on normal skin and belongs to the types frequently associated with skin cancers of Epidermodysplasia verruciformis patients. One factor by which this anatomical tropism could be determined is the regulation of HPV gene expression in the host cell. The HPV long control region (LCR) contains cis-responsive elements that regulate HPV transcription and the epithelial tropism of HPV is determined by epithelial specific constitutive enhancers in the LCR. Since HPV-16 and other types infecting the mucosa differ in host cell from HPV types infecting skin, it has been hypothesized that it is the combination of ubiquitous transcription factors working in concert in the host cell that determines the cell-type-specific expression. To study if HPV tropism could be determined by differences in transcriptional regulation we have cloned the transcriptional regulating region, LCR, from HPV-16 and HPV-5 and studied the activation of a reporter gene in cell lines with different origin. To analyse promoter activity we transfected the plasmids into four different cell lines; HaCaT, C33A, NIKS and W12E and the efficiency of HPV-5 and HPV-16 LCR in the different cell lines was compared. In HaCaT cells, with a skin origin, the HPV-5 LCR was two-fold more efficient in transcriptional activation compared to the HPV-16 LCR. In cervical W12E cells the HPV-16 LCR was almost 2-fold more effective in activating transcription compared to the HPV-5 LCR. The ability to initiate transcription in the other cell lines was independent on cell origin and HPV-type.