Regulation of human papillomavirus type 16 early gene expression in trophoblastic and cervical cells

We compared the outcome of different cellular and viral factors on the regulation of the HPV-16 early viral gene expression in trophoblastic and cervical cancer cells. A high variability of the long control (LCR) activity was observed, prompting us to evaluate the role of secreted factors in the control of the early gene expression in trophoblastic cell lines. Endogenous progesterone and exogenous dexamethasone were found to activate LCR driven transcriptional activity. Since host cells express HPV early proteins to regulate LCR activity, we investigated the effect of the combined HPV-16 early proteins on the LCR driven transcription and the possible involvement of E2. A physiological level of HPV-16 early proteins expression strongly induced the LCR driven reporter activity. According to mutational analysis, E1 and E2 proteins, indispensable for viral replication, were not involved in LCR extrachromosomal transcriptional regulation. This suggests that E5 and/or E6 and/or E7, consequently, activated viral transcription.