Department of Virology, The National Institute for Medical Research, The Ridgeway Mill Hill, London NW7 1AA, UK.
Carcinogenesis. 2010 May;31(5):918-26. doi: 10.1093/carcin/bgq027. Epub 2010 Feb 1.
A common feature shared between several human cancer-associated viruses, such as Epstein-Barr virus, Hepatitis B virus and Hepatitis C virus, and Human papillomavirus (HPV) is the ability to reduce the expression of cellular E-cadherin. Since E-cadherin is used by Langerhans cells to move through the stratified epithelium, its reduction may affect the efficiency by which the immune system responds to HPV infection and the length of persistent HPV infections. We observed that the E7 protein of this virus (HPV16) is most efficient at reducing E-cadherin levels. This E7 activity is independent of retinoblastoma protein or AP-2alpha degradation. Instead it is associated with augmentation of cellular DNA methyltransferase I (Dnmt1) activity. Significantly, inhibition of Dnmt activity re-established E-cadherin levels of the cells, presenting the possibility that similar epigenetic intervention clinically may be a way to re-establish the influx of Langerhans cells into infected epithelium to counteract HPV persistence.
几种与人类癌症相关的病毒（如 Epstein-Barr 病毒、乙型肝炎病毒和丙型肝炎病毒以及人类乳头瘤病毒（HPV））的一个共同特征是能够降低细胞 E-钙粘蛋白的表达。由于朗格汉斯细胞通过分层上皮迁移时使用 E-钙粘蛋白，因此其减少可能会影响免疫系统对 HPV 感染的反应效率和持续性 HPV 感染的时间。我们观察到该病毒（HPV16）的 E7 蛋白在降低 E-钙粘蛋白水平方面最为有效。这种 E7 活性不依赖于视网膜母细胞瘤蛋白或 AP-2alpha 的降解。相反，它与细胞 DNA 甲基转移酶 I（Dnmt1）活性的增强有关。重要的是，抑制 Dnmt 活性可重建细胞的 E-钙粘蛋白水平，提示临床上类似的表观遗传干预可能是重建朗格汉斯细胞进入感染上皮以对抗 HPV 持续性的一种方法。
