乙型肝炎病毒（HBV）感染是一个严重的全球性健康问题，但HBV感染及其导致的慢性肝炎的发生机制仍不明确。DTX1是一种E3泛素连接酶，在调节宿主T细胞与乙肝病毒免疫反应机制中起着至关重要的作用。抗菌肽DEFB1是DTX1的泛素化底物之一，但其在乙肝感染中的作用和相关机制尚未明确。在我们的前期研究中发现DTX1、DEFB1基因水平在慢性乙肝病人的肝组织中表达显著升高，而DEFB1蛋白水平降低，且HBV患者DEFB1蛋白水平与DTX1负相关，因此，我们推测，DTX1可能通过泛素化降解DEFB1从而调控HBV感染。本研究拟以DTX1基因敲除小鼠、L02和HepG2.2.15细胞系为研究对象，通过构建HBV感染小鼠模型和细胞模型，阐明DTX1和DEFB1在HBV感染中的作用，并探索DTX1泛素化降解DEFB1的分子机制。本研究将帮助我们为慢性乙肝的治疗寻找新的靶向分子。

Infection of hepatitis B virus is a serious global health issue, but the mechanisms of HBV infection and hepatitis occurrence still remain vague. DTX1 is an E3 ubiquitin ligase, which plays important roles in regulating T cell function and HBV immunity. DEFB1 is one of the substrates of DTX1-mediated ubiquitination, but its role in HBV infection remains unknown. In our previous study we found that the expression levels of DTX1 and DEFB1 genes were significantly elevated in HBV-infected patients, whereas the protein level of DEFB1 significantly dropped. Moreover, the protein levels of DEFB1 in HBV-infected patients were negatively correlated with that of DTX1. Taken together, we speculate that DTX1 may regulate HBV infection via mediating the ubiquitination and degradation of DEFB1. In this study, DTX1 knockout mice, L02 and HepG2.2.15 cells will be used to illustrate the role of DTX1 and DEFB1 in HBV infection, molecular biology experiments will be conducted to explore the mechanism of DEFB1 ubiquitination mediated by DTX1. This study will help us to look for the novel therapeutic target to chronic HBV hepatitis.