病毒特异性T细胞耗竭是HBV持续存在的重要原因，但具体机制未明。KLRG1是NK细胞和T细胞的一种抑制性受体，其活化可抑制NK细胞和T细胞功能。近年发现E-cadherin是KLRG1的配体，可活化KLRG1信号。我们在前期工作中，发现细胞中HBV可以下调ZEB2的水平并促进E-cadherin的表达，HBV感染者血液中sE-cadherin水平明显增高。据此，本项目提出假说：HBV下调ZEB2的水平，从而促进E-cadherin的表达，通过激活KLRG1通路引起病毒特异性CD8+ T细胞耗竭，导致HBV持续感染。为此，本项目拟综合利用细胞实验、动物实验和临床标本，探讨HBV上调E-cadherin的机制及临床意义，重点解析E-cadherin/LKRG1通路在HBV特异性CD8+细胞耗竭中的作用机制。本项目的实施，将有助于深入理解病毒与宿主的相互关系，并为研发新的治疗靶点提供思路。

Virus specific T cell exhaustion is one of the main causes for Hepatitis B virus persistent infection, and the mechanism has not been fully elucidated yet. Killer cell lectin-like receptor G1 (KLRG1) is an inhibitory receptor molecule, which is mainly expressed in NK and T cell and produces inhibitory signals to negatively regulate the function of immune cells. E-cadherin is a well known intercellular adhesion molecule, but its role in immunomodulation is less known. Recently, E-cadherin wss found to be the ligand of KLRG1 and take part in T cell exhaustion. Our early work discovered that Hepatitis B virus (HBV) increased the expression of E-cadherin accompanied with down-regulation of ZEB2. In addition, sE-cadherin increased in sera of patients with HBV infection. Therefore, we proposed a hypothesis: HBV enhances E-cadherin expression by down-regulation of ZEB2, and the enhanced E-cadherin stimulates KLRG1 pathway and induces virus specific CD8+ T cell exhaustion, which in turn promotes persist infection. This project aims to elaborate the mechanism that HBV increase the expression of E-cadherin via down-regulation of ZEB2 and the clinical significance in CD8+ T cell exhaustion through stimulating KLRG1. This research may enrich our knowledge about interaction between virus and host and provide an explanation for HBV chronic infection. Furthermore, it may help to explore new therapy targets.