人乳头瘤病毒(HPV)感染至今是一种难治且易复发的传染性疾病，常引发皮肤黏膜增生性病变、宫颈癌及其他肿瘤。宿主免疫系统防御和调控HPV感染的机制知之甚少，因而导致缺乏有效防御手段和治疗方法。Toll样受体（TLR）介导的自噬作为天然免疫的重要部分，但在HPV感染的免疫应答中的作用并不明确。 基于我们对HPV感染中TLR作用的研究，本项目，拟通过建立HPV病毒感染角质形成细胞(KC)的模型，分析研究HPV感染对宿主细胞自噬状态；研究TLR介导的自噬信号通路。建立HPV 早期蛋白的KC表达模型，分析TLR通路下游基因和自噬基因的表达和功能，以期阐明HPV感染过程中，宿主细胞的自噬调控机制。进一步采用不同TLR激动剂、自噬抑制剂及诱导剂影响细胞自噬，了解自噬的诱导及抑制对HPV感染的影响。本研究将揭示HPV感染的自噬及其调控机制，促进HPV感染的防御机制研究，具有较高的学术价值和潜在应用价值。

Human papilloma virus (HPV) infection is still a refractory, palindromic and infectious disease which often causes skin mucous membrane hyperplasia, cervical cancer and other tumors. The host immune system defension and regulation mechanisms of HPV infection poorly understood, results in lacking of effective defense means and treatment methods. Toll-like receptor (TLR) mediated autophagy is an important part of innate immunity, but the functions of immune response in HPV infection remains unclear. Based on our investigation of the relationship between HPV infection and TLR signaling pathway, in this project, the reaserch model of keratinocytes (KC) infected by HPV pseudovirus will be established, to analysis the autophagy level of the host cell after HPV infection, and reaserch the autophagy signaling pathway mediated by TLR as well. The reaserch model of keratinocytes (KC) expressed early genes of HPV also will be established, to analysis the downstream genes' expression and functions of TLR and autophagy, in order to clarify the autophagy regulation mechanism of host cells in HPV infection. Furthermore, different TLR agonists, inhibitors and inducers of autophagy will be used to change the autophagy level of the host cell and to clarify the effect on virus infection. This research will reveal the regulation mechanism of autophagy in HPV infection, and also will promote the investigation of defense mechanism in HPV infection, has a high academic value and potential application value.