课题组前期研究中发现负性分子PD-1的高表达与HBV持续感染有关，但导致PD-1增高的分子机制不明。国内外研究新近证实PD-1的低甲基化是造成其高表达的原因，结合课题组前期发现miR-29在慢性HBV感染者中表达增高的现象，以及目前miR-29在感染免疫中发挥负性调节作用的最新研究热点，推测miR-29通过抑制其靶基因DNMT诱导PD-1的低甲基化和高表达，介导病毒免疫逃逸。课题组以慢性HBV感染者及病毒自发清除者为研究对象，分析其miR-29、PD-1表达及PD-1甲基化情况，并用miR-29模拟物转染细胞及shRNA技术进行体外试验证实推论。项目预期将揭示，miR-29通过抑制甲基化转移酶DNMT，造成负性分子PD-1低甲基化，从而引起负性信号异常活化，诱导宿主免疫耐受和病毒免疫逃逸。项目的研究成果对于研究表观修饰在乙肝病毒免疫逃逸中的作用机制和探索新的治疗方案具有重要意义。

Our existing results indicate that over-expression of co-suppression molecule PD-1 was associated with HBV persistence, but the mechanism has not been elucidated yet. One newly proved reason is that over-expression of PD-1 is related to its de-methylation. In consideration of our existing discovery that miR-29 was increased in chronic HBV infection, and that negative regulatory role of miR-29 in infection immunity becomes research hotspot, we speculate that miR-29 induces de-methylation and over-expression of PD-1 by suppress its target gene DNMT, this leads to immune escape of HBV. Our group plans to explore expression level of miR-29, PD-1 and methylation of PD-1 in chronic HBV infection and spontaneous clearance, and hope to confirm our deduction by cell model and shRNA method in vitro. The study expects to reveal that miR-29 could suppress DNMT, induce de-methylation and over-expression of PD-1, results in immune escape of HBV. These research findings have great significance in mechanism and treatment exploration.