消除乙型肝炎病毒感染危害的关键科学问题与突破路径

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关键词：乙型肝炎病毒；共价闭合环状DNA；分子机制基金项目：新发突发与重大传染病防控国家科技重大专项（2025ZD01906700）

Keyscientific issuesandbreakthroughpathstoeliminate theharmofhepatitis B virusinfection

WANG Yixue 1，2 ，PENG Bol，2 ，WEI Lei，LONG Quanxin4，XIA Yuchen’，SUN Yinyan χl，2l，2 ，LI Wenhui1，2

1.NationalIstiutefgicalScienes，Beig26Cin；singaIstiuteofudisciplinaryBiomedicalch TsinghuaUniversityBeijingoo84，China；.CnterforIfectiousDiseaseResearch，ShoolofMedicine，WestlakeUieity Hangzhou3loo24，China；4.KeyLaboratoryofMolecular Biologyfor Infectious Diseases（MinistryofEducation），Institutefor ViralHepatitis，DepartmentofInfectiousDiseases，TheSecondAflitedHospital，ChongqingedicalUniversity，Coging 400010，China；5.TaiKang Medical School，Wuhan University，Wuhan 43o071，China

Corresponding author：LIWenhui，liwenhui@nibs.ac.cn（ORCID：O000-0003-1305-7404）

Abstract：HepatitisBvirus （HBV）exclusively infects liver parenchymal celsand formscovalently closedcircular DNA （cccDNA）withintheirnuclei.HBVcccDNAservesastheessntial templateforviralgenetranscription，thesolesourceofprogeny virus production，andthekeydriverofviralantigenexpresion，anditisthemolecularbasisforthepersistenceofHBVifection. Therefore，eliminationand/orfunctionalsilencingofccDNAis thekeytoeradicatechronicHBVinfection.Thisarticlediscuses thecriticalscientificissues thatneedtobesolvedduring eliminationoftheharmofHBVinfectionfromtheperspectivesof the synthesis，transcriptionandclearanceofccDA，aswellastheimpactofonparenchyalcelloncDA，inordertoprovide areferencefor eradicatingHBVinfectioninthefuture.

KeyWords：HepatitisB Virus；Covalently Closed Circular DNA；Molecular Mechanisms

Researchfunding：PreventionandControlof Emergingand Major Infectious Diseases-National Scienceand Technology Major Project （2025ZD01906700）

乙型肝炎病毒（hepatitisBvirus，HBV）在全球范围内约感染2.54亿人[1]。（剩余15286字）