乙型肝炎病毒感染的自然控制和清除

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DOI：10.12449/JCH260102

关键词：乙型肝炎病毒；共价闭合环状DNA；抗病毒免疫基金项目：国家自然科学基金（82372234，32570162）；国家重点研发计划（2022YFA1303600）

NaturalcontrolandclearanceofhepatitisBvirusinfection

YEJianyu I，2 ，WANG Bing I，2 ，GU Leyan I，2 ， FAN Yingting I，2 ， CHEN Jieliang1，2

1.DepartmentofMedicalMicrobiologyandParasitology，ScholofBasicMedicalSciences，Shanghai MedicalCollge，Fudan University，Shanghai ，China；2.MOE/NHC/CAMsKeyLaboratoryof Medical Molecular Virology，Shanghai ，China

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

Abstract：Hepatitis Bvirus（HBV）isaunique hepatotropicDNAvirusthatforms covalentlyclosedcircularDNA within the nucleusofhepatocytesandcanpartiallintegrateintothehostgenome，establishingthemolecularbasisforpersistentviral infection.HBVinfectionandreplicationdependsonmultiplehepatocyte-enriched hostfactorsandismodulatedbythehepatic microenvironment.The hostachieves natural controlandclearanceof HBVthrough variousmechanisms，includingcytolytic eliminationmediatedbycellularimmunitysuch ascytotoxic Tlymphocytesandnaturalkilercells，inateimmunityand noncytolyticclearancedriven byinterferonsandvariouscytokines，andantibody-mediated protectionandclearanceaspartof humoralimmuneresponse.Inaddition，intracellularrestrictionfactorsandpathways，hepatocyte turnoverthroughdivisionand replacement，andchanges inthe hepatic microenvironment（suchastheincrease inmatrix stiffess）collectively influence the eficiencyandoutcomeofviralcontrolandclearane.Thisarticleclarifiesandelaboratesonrelatedmechanisms，soastodeepen theunderstandingof HBVchronicity，spontaneousresolution，andcureandprovideatheoreticalbasis foroptimizingclinical management and developing novel therapeutic strategies.

KeyWords：HepatitisBVirus；Covalently Closed Circular DNA；Antiviral Immunity

Researchfunding：National Natural ScienceFoundationof China（82372234，32570162）;National KeyR&DProgramof China （2022YFA1303600）

乙型肝炎病毒（hepatitisBvirus，HBV）长期威胁人类健康，其感染慢性化可导致慢性乙型肝炎，并进一步发展为肝硬化及肝细胞癌，造成沉重的疾病负担[1]。（剩余16925字）