慢性乙型肝炎（Chronic hepatitis B ，CHB）是肝纤维化、肝硬化及肝细胞癌的主要风险因素。目前尽管采用干扰素和核苷类似物等治疗手段，但仍难以彻底治愈，因此探究HBV感染的免疫机制，特别是宿主遗传背景的作用，对开发新治疗策略至关重要。本研究通过AAV8-rcccDNA小鼠模型，考察了FVB/N×C57BL/6与DBA/2×C57BL/6两种遗传背景小鼠对HBV感染免疫反应的差异。结果显示FVB/N×C57BL/6小鼠呈现免疫耐受状态，表现为持续的HBsAg表达和低HBsAb水平。相反，DBA/2×C57BL/6小鼠模拟了急性感染恢复，具体为HBsAg转阴、HBsAb阳性及病毒复制中低水平。本研究证实在HBV感染治疗与研究中考虑宿主遗传背景的必要性，并指出适应性免疫系统调控在HBV治愈中的潜力，AAV8-rcccDNA小鼠模型的改进为模拟人类HBV感染免疫状态提供了有效工具，有利于 HBV 治疗策略的优化和研发。

Chronic hepatitis B (CHB) is a major risk factor for liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Despite the use of interferons and nucleoside analogues as treatment options, a complete cure remains elusive, making the exploration of HBV infection's immunological mechanisms, especially the role of host genetic background, crucial for developing new therapeutic strategies. This study utilized the AAV8-rcccDNA mouse model to investigate the differences in immune response to HBV infection between mice of two genetic backgrounds, FVB/N×C57BL/6 and DBA/2×C57BL/6. The results showed that FVB/N×C57BL/6 mice exhibited an immune-tolerant state, characterized by persistent HBsAg expression and low levels of HBsAb. In contrast, DBA/2×C57BL/6 mice simulated the recovery phase of acute infection, specifically showing HBsAg seroclearance, HBsAb positivity, and mid-to-low levels of viral replication. This study underscores the necessity of considering the host genetic background in HBV infection treatment and research and highlights the potential of adaptive immune system regulation in achieving HBV cure. The improvement of the AAV8-rcccDNA mouse model provides an effective tool for simulating the human immune state during HBV infection, facilitating the optimization and development of HBV treatment strategies.