我国宫颈癌防控形势严峻，难点在于无法阻遏HPV持续感染所致宫颈病变进展。HPV E7癌蛋白在病毒逃避宿主免疫防御并致宫颈病变的过程中发挥重要作用。此前我们发现HPV E7癌蛋白能结合LSD1并影响其功能，LSD1则能通过调控CD47启动子区域的组蛋白甲基化水平来增强其表达。研究发现，CD47能与免疫细胞上的受体结合参与诱导“别我吃”抑制性免疫信号。我们推测，HR-HPV借由HPV E7-LSD1-CD47信号使受感染细胞不被免疫清除，建立持续感染进而导致宫颈病变。本项目拟首先分析临床样本中LSD1、CD47表达与HPV感染转归及宫颈病变发生发展的相关性，探讨其作为分子标志物的价值；然后通过基因敲除等关键技术和人源化NSG鼠、转基因鼠的各级宫颈病变模型，从体内外两方面探讨HPV E7与LSD1结合调控CD47致病毒免疫逃逸的关键信号通路与效应特征，为HR-HPV防控新策略的建立提供科学依据。

The prevention and control of cervical cancer in China is a big challege. The difficulty lies in the inability to repress the progression of cervical lesions caused by persistent HPV infection. HPV E7 oncoprotein plays an important role in the process of virus evading host immune defense and causing cervical lesions. Previously, we found that HPV E7 oncoprotein can bind to LSD1 and affect its function, and LSD1 can increase CD47 expression by regulating histone methylation level in the promoter region. The study found that CD47 binds to receptors on immune cells and is involved in inducing an "indiscriminate immune" inhibitory immune signal. We hypothesized that HR-HPV would protect the infected cells from immune clearance by HPV E7-LSD1-CD47 signaling, establishing a persistent infection leading to cervical lesions. This project will firstly analyze the correlation between the LSD1/ CD47 expression in clinical samples and the development of HPV infection and cervical lesions to explore its value as a molecular marker, and then explored the key signaling pathways and effect characteristics of HPV E7 and LSD1 binding to CD47-induced viral immune escape from both in vitro and in vivo by imploring the key technologies such as gene knockout and humanized NSG mice, The cervical lesion models of transgenic mice, providing a scientific basis for the establishment of a new HR-HPV prevention and control strategy.