Cell-type specific transcriptional activities among different papillomavirus long control regions and their regulation by E2

This study systematically examined the viral long control region (LCR) activities and their responses to E2 for human papillomavirus (HPV) types 11, 16, and 18 as well as bovine papillomavirus 1 (BPV1) in a number of different cell types, including human cervical cancer cell lines, human oral keratinocytes, BJ fibroblasts, as well as CV1 cells. The study revealed cell- and virus-type specific differences among the individual LCRs and their regulation by E2. In addition, the integration of the LCR into the host genome was identified as a critical determinant for LCR activity and its response to E2. Collectively, these data indicate a more complex level of transcriptional regulation of the LCR by cellular and viral factors than previously appreciated, including a comparatively low LCR activity and poor E2 responsiveness for HPV16 in most human cells. This study should provide a valuable framework for future transcriptional studies in the papillomavirus field.