人乳头瘤病毒16 E6蛋白可保护细胞或使细胞对肿瘤坏死因子（TNF）更敏感：剂量的影响。

The human papillomavirus 16 E6 protein can either protect or further sensitize cells to TNF: effect of dose.

作者信息

Filippova M, Brown-Bryan T A, Casiano C A, Duerksen-Hughes P J

机构信息

Department of Biochemistry and Microbiology, Center for Molecular Biology and Gene Therapy, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA.

出版信息

Cell Death Differ. 2005 Dec;12(12):1622-35. doi: 10.1038/sj.cdd.4401678. Epub 2005 Jun 3.

High-risk strains of human papillomavirus, including HPV 16, cause human cervical carcinomas, due in part to the activity of their E6 oncogene. E6 interacts with a number of cellular proteins involved in host-initiated apoptotic responses. Paradoxically, literature reports show that E6 can both protect cells from and sensitize cells to tumor necrosis factor (TNF). To examine this apparent contradiction, E6 was transfected into U2OS cells and stable clones were treated with TNF. Intriguingly, clones with a high level of E6 expression displayed an increased sensitivity to TNF by undergoing apoptosis, while those with low expression were resistant. Furthermore, TNF treatment of cells in which the expression of E6 was regulated by the addition of doxycycline demonstrated clearly that while low levels of E6 protect cells from TNF, high levels sensitize cells. Together, these results demonstrate that virus-host interactions can be complex and that both quantitative and qualitative aspects are important in determining outcome.

包括人乳头瘤病毒16型（HPV 16）在内的高危型人乳头瘤病毒会引发人类宫颈癌，部分原因是其E6癌基因的活性。E6与许多参与宿主引发的凋亡反应的细胞蛋白相互作用。矛盾的是，文献报道显示E6既能保护细胞免受肿瘤坏死因子（TNF）的影响，又能使细胞对其敏感。为了研究这一明显的矛盾，将E6转染到U2OS细胞中，并对稳定克隆用TNF进行处理。有趣的是，E6表达水平高的克隆通过凋亡对TNF表现出更高的敏感性，而低表达的克隆则具有抗性。此外，用强力霉素调节E6表达的细胞经TNF处理清楚地表明，低水平的E6保护细胞免受TNF影响，而高水平则使细胞敏感。这些结果共同表明，病毒与宿主的相互作用可能很复杂，并且在决定结果方面，数量和质量方面都很重要。