Ottinger Matthias, Smith Jennifer A, Schweiger Michal-Ruth, Robbins Dana, Powell Maria L C, You Jianxin, Howley Peter M
Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Virology. 2009 Dec 20;395(2):161-71. doi: 10.1016/j.virol.2009.09.027.
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.
本研究系统地检测了人乳头瘤病毒11型、16型和18型以及牛乳头瘤病毒1型(BPV1)的病毒长控制区(LCR)活性及其对E2的反应,检测在多种不同细胞类型中进行,包括人宫颈癌细胞系、人口腔角质形成细胞、BJ成纤维细胞以及CV1细胞。该研究揭示了各个LCR之间细胞和病毒类型特异性差异以及它们受E2的调控情况。此外,LCR整合到宿主基因组被确定为LCR活性及其对E2反应的关键决定因素。总体而言,这些数据表明,细胞和病毒因子对LCR的转录调控水平比之前认为的更为复杂,包括在大多数人类细胞中,HPV16的LCR活性相对较低且对E2反应较差。本研究应为乳头瘤病毒领域未来的转录研究提供有价值的框架。