title: Epigallocatechin-3-gallate opposes HBV-induced incomplete autophagy by enhancing lysosomal acidification, which is unfavorable for HBV replication.
abstract: Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, exhibits diverse beneficial properties, including antiviral activity. Autophagy is a cellular process that is involved in the degradation of long-lived proteins and damaged organelles. Recent evidence indicates that modulation of autophagy is a potential therapeutic strategy for various viral diseases. In the present study, we investigated the effect of EGCG on hepatitis B virus (HBV) replication and the possible involvement of autophagy in this process. Our results showed that HBV induced autophagosome formation, which was required for replication of itself. However, although EGCG efficiently inhibited HBV replication, it enhanced, but not inhibited, autophagosome formation in hepatoma cells. Further study showed that HBV induced an incomplete autophagy, while EGCG, similar to starvation, was able to induce a complete autophagic process, which appeared to be unfavorable for HBV replication. Furthermore, it was found that HBV induced an incomplete autophagy by impairing lysosomal acidification, while it lost this ability in the presence of EGCG. Taken together, these data demonstrated that EGCG treatment opposed HBV-induced incomplete autophagy via enhancing lysosomal acidification, which was unfavorable for HBV replication.
authors.affiliation: Institute for Immunobiology, Department of Immunology, Shanghai Medical College of Fudan University, Shanghai 200032, P.R. China.
authors.forename: L
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Institute for Immunobiology, Department of Immunology, Shanghai Medical College of Fudan University, Shanghai 200032, P.R. China.
authors.forename: J
authors.initials: J
authors.lastname: Hu
authors.affiliation: Institute for Immunobiology, Department of Immunology, Shanghai Medical College of Fudan University, Shanghai 200032, P.R. China.
authors.forename: W
authors.initials: W
authors.lastname: Shu
authors.affiliation: Institute for Immunobiology, Department of Immunology, Shanghai Medical College of Fudan University, Shanghai 200032, P.R. China.
authors.forename: B
authors.initials: B
authors.lastname: Gao
authors.affiliation: 1] Institute for Immunobiology, Department of Immunology, Shanghai Medical College of Fudan University, Shanghai 200032, P.R. China [2] Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215006, P.R. China.
authors.forename: S
authors.initials: S
authors.lastname: Xiong
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D000071187:Autophagy-Related Protein 5; D000071193:Autophagy-Related Protein 7; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000235:genetics; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics; D010936:Plant Extracts / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D013662:Tea / Q000737:chemistry; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics; D014758:Viral Core Proteins / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects*
chemical_list: C502778:ATG5 protein, human; D000998:Antiviral Agents; D000071187:Autophagy-Related Protein 5; D004279:DNA, Viral; D008869:Microtubule-Associated Proteins; D010936:Plant Extracts; D034741:RNA, Small Interfering; D013662:Tea; D014758:Viral Core Proteins; D002392:Catechin; C045651:epigallocatechin gallate; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes