摘要Epigallocatechin-3-gallate(EGCG),a major polyphenolic compound in green tea,exhibits anti-viral activity against multiple viruses,including hepatitis B virus(HBV).However,its role in HBV replication and the underlying mechanisms remain incompletely understood.In this study,we investigated the effects of EGCG on HBV replication and its modulation of auto-phagy using two established HBV cell models.Our results show that EGCG significantly re-duces secreted levels of hepatitis B surface antigen(HBsAg)and HBV deoxyribonucleic acid(DNA),as well as intracellular HBV DNA replicative intermediates,encapsidated pregenomic ribonucleic acid(pgRNA),and core protein(HBc),without affecting total HBV messenger RNAs(mRNAs)or pgRNA levels.EGCG enhances autophagic flux,evidenced by increased autophagosome formation and accelerated turnover of the selective autophagy receptor p62 and LC3-Ⅱ.This enhanced autophagy promotes HBc degradation.Pharmacological inhibition of autophagy with 3-methyladenine(3-MA),chloroquine(CQ),or bafilomycin A1(BafA1)ab-olished the suppressive effect of EGCG on HBV.Notably,treatment with CQ or BafA1 together with EGCG markedly increased HBV production by blocking autophagic degradation and indu-cing accumulation of autophagosomes-effects similar to those induced by the autophagy ac-tivator rapamycin,which facilitates HBV replication.Mechanistically,EGCG activates the ad-enosine 5'-monophosphate-activated protein kinase(AMPK)/transcription factor EB(TFEB)signaling axis,leading to enhanced lysosomal biogenesis and ATP production,thereby pro-moting autophagic clearance.Pharmacological or genetic inhibition of AMPK attenuated TFEB transcriptional activity,suppressed lysosomal biogenesis and ATP generation,impaired auto-phagic degradation,increased HBc levels,and ultimately enhanced HBV replication.Con-versely,pharmacological activation of AMPK produced opposing effects.These findings re-veal a novel mechanism by which EGCG inhibits HBV:EGCG promotes autophagic degrada-tion of the viral core protein via activation of the AMPK/TFEB signaling pathway.