乙型肝炎病毒感染的自然控制和清除

叶建宇; 王冰; 顾乐言; 樊映廷; 陈捷亮

doi:10.12449/JCH260102

乙型肝炎病毒感染的自然控制和清除

DOI: 10.12449/JCH260102

叶建宇^{1, 2},
王冰^{1, 2},
顾乐言^{1, 2},
樊映廷^{1, 2},
陈捷亮^{1, 2, , ,}

1.
复旦大学上海医学院基础医学院病原生物学系，上海 200032
2.
国家卫生健康委员会/教育部/医科院医学分子病毒学重点实验室，上海 200032

基金项目:

国家自然科学基金 (82372234);

国家自然科学基金 (32570162);

国家重点研发计划 (2022YFA1303600)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：叶建宇、王冰、顾乐言、樊映廷负责整理文献资料及撰写论文；陈捷亮负责指导撰写并修改论文。

详细信息

通信作者:
陈捷亮，jieliangchen@fudan.edu.cn （ORCID： 0000-0002-9647-0239）

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出版历程
- 收稿日期: 2025-10-31
- 录用日期: 2025-12-01
- 出版日期: 2026-01-25

Natural control and clearance of hepatitis B virus infection

Jianyu YE^{1, 2},
Bing WANG^{1, 2},
Leyan GU^{1, 2},
Yingting FAN^{1, 2},
Jieliang CHEN^{1, 2
, ,
,}

1.
Department of Medical Microbiology and Parasitology，School of Basic Medical Sciences，Shanghai Medical College，Fudan University，Shanghai 200032，China
2.
MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology，Shanghai 200032，China

Research funding:

National Natural Science Foundation of China (82372234);

National Natural Science Foundation of China (32570162);

National Key R&D Program of China (2022YFA1303600)

More Information

Corresponding author: CHEN Jieliang， jieliangchen@fudan.edu.cn （ORCID： 0000-0002-9647-0239）

摘要

摘要: 乙型肝炎病毒（HBV）是一种独特的嗜肝DNA病毒，在肝细胞核内形成共价闭合环状DNA并可部分整合入宿主基因组，构成病毒持续感染的分子基础。HBV感染复制依赖多种肝细胞富集因子及微环境调控。宿主通过多种方式实现对HBV的自然控制和清除，包括以细胞毒性T细胞及自然杀伤细胞等细胞免疫介导的溶细胞性清除，以干扰素和各类细胞因子驱动的天然免疫与非溶细胞性清除，以及体液免疫中抗体介导的保护与清除。此外，细胞内限制性因子和通路、肝细胞分裂更新及基底硬度等肝脏微环境变化亦共同影响病毒控制和清除的效率与结局。本文深入阐明并动态解析相关机制，将有助于加深理解乙型肝炎慢性化及自愈和治愈的过程，为优化诊疗及研发新型干预策略提供理论基础。
- 乙型肝炎病毒 /
- 共价闭合环状DNA /
- 抗病毒免疫
Abstract: Hepatitis B virus （HBV） is a unique hepatotropic DNA virus that forms covalently closed circular DNA within the nucleus of hepatocytes and can partially integrate into the host genome， establishing the molecular basis for persistent viral infection. HBV infection and replication depends on multiple hepatocyte-enriched host factors and is modulated by the hepatic microenvironment. The host achieves natural control and clearance of HBV through various mechanisms， including cytolytic elimination mediated by cellular immunity such as cytotoxic T lymphocytes and natural killer cells， innate immunity and noncytolytic clearance driven by interferons and various cytokines， and antibody-mediated protection and clearance as part of humoral immune response. In addition， intracellular restriction factors and pathways， hepatocyte turnover through division and replacement， and changes in the hepatic microenvironment （such as the increase in matrix stiffness） collectively influence the efficiency and outcome of viral control and clearance. This article clarifies and elaborates on related mechanisms， so as to deepen the understanding of HBV chronicity， spontaneous resolution， and cure and provide a theoretical basis for optimizing clinical management and developing novel therapeutic strategies.
- Hepatitis B Virus /
- Covalently Closed Circular DNA /
- Antiviral Immunity

HTML全文

注： HBV是一种嗜肝DNA病毒，感染肝细胞后形成cccDNA和整合DNA，转录产生多种HBV RNA以合成病毒抗原和子代病毒，过程中多种肝细胞富集因子对感染复制的建立与维持具有重要作用。宿主通过溶细胞性、非溶细胞性、限制性因子/通路、肝细胞分裂更新及抗病毒抗体等多种机制控制和清除HBV，期间各类免疫细胞、细胞因子及细胞外基底硬度变化等协同作用。cccDNA，共价闭合环状DNA；HBV，乙型肝炎病毒；NTCP，钠离子-牛磺胆酸共转运蛋白；HNF-4α，肝细胞核因子4α；C/EBP-α，CCAAT增强子结合蛋白α；Treg，调节性T细胞；MHC，主要组织相容性复合体；CTL，细胞毒性T细胞；cDC1，Ⅰ型经典树突状细胞；DC，树突状细胞；IFN-γ，干扰素γ；NKT，自然杀伤T细胞；NK，自然杀伤细胞。

图 1 HBV感染与控制清除机制示意图

Figure 1. Schematic of HBV infection and the mechanisms of viral control and clearance

下载: 全尺寸图片幻灯片

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