人乳头瘤病毒E6/E7蛋白影响Toll样受体信号通路的表观遗传学调控机制研究

人乳头瘤病毒（HPV）感染与皮肤黏膜良性增生性病变、宫颈癌及其他肿瘤的发生关系密切。由于人们对宿主免疫系统防御和调控HPV感染的机制知之甚少，导致迄今缺乏切实有效的HPV感染防治手段。研究表明，HPV感染引起的Toll样受体（TLR）信号通路改变与表观遗传修饰关系密切。基于我们对HPV感染中TLR作用的研究，本项目拟建立宫颈癌细胞系C-33A及HT-3的HPV16型E6/E7基因表达模型和人原代角质形成细胞及HaCaT细胞的HPV11型E6/E7基因表达模型，检测细胞内TLR信号通路关键蛋白的表达及其表观遗传修饰状态，以期阐明HPV感染过程中宿主细胞如何通过表观遗传修饰调节TLR信号通路进而引发免疫逃逸。研究结果有望揭示HPVE6/E7蛋白通过表观遗传学调控TLR信号通路的机制，丰富HPV免疫致病机制的研究，具有较高的学术价值和潜在应用价值。

Infection with human papillomavirus (HPV) often causes cutaneous benign lesions, cervical cancer, and a number of other tumors. The mechanisms of host immune system to prevent and control HPV infection still remain poorly understood, which leads to the lack of effective anti-viral therapeutic strategies. It has been demonstrated that the deregulated Toll-like receptor (TLR) signaling pathways during HPV infection are very relevant to epigenetic alterations. In this study, cervical cancer cell lines (C-33A and HT-3) expressing HPV16E6/E7 genes as well as human keratinocytes and HaCaT cells expressing HPV11E6/E7 genes will be established. We will then analyze the expression and epigenetic modifications of some critical proteins in the cellular TLR signaling pathways. The results would illustrate the possible mechanisms of HPVE6/E7 proteins to regulate TLR signaling pathways via epigenetic modulations. Therefore, this project shows outstanding academic significance and potential application values.