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.

Reactive Oxygen Species-Mediated c-Jun NH 2 -Terminal Kinase Activation Contributes to Hepatitis B Virus X Protein-Induced Autophagy via Regulation of the Beclin-1/Bcl-2 Interaction

“…Evidence indicates that HBx plays a crucial role in HBV-induced autophagosome formation, which is required for HBV replication (28)(29)(30)(31)(32). As our data revealed that HBx induces autophagy via the ROS-JNK signaling pathway, we further examined the role of this signaling pathway in HBV-induced autophagy and its replication.…”

“…Recent studies have shown that autophagy is an important host factor in the regulation of the replication of diverse viruses, such as dengue virus, poliovirus, influenza virus A, and coxsackievirus B3 virus, as well as HBV (25)(26)(27)(28)(29)(30)(31)(32). Evidence indicates that HBV can activate autophagosome formation, which is required for its own replication (28)(29)(30)(31)(32). Furthermore, HBx appears to play an important role in HBV-induced autophagosome formation (28,(33)(34)(35)(36).…”

“…Accumulating evidence indicates that autophagy is involved in various pathological processes, including cancer and metabolic and neurodegenerative disorders (23,24). Recent studies have shown that autophagy is an important host factor in the regulation of the replication of diverse viruses, such as dengue virus, poliovirus, influenza virus A, and coxsackievirus B3 virus, as well as HBV (25)(26)(27)(28)(29)(30)(31)(32). Evidence indicates that HBV can activate autophagosome formation, which is required for its own replication (28)(29)(30)(31)(32).…”

Hepatitis B virus dampens autophagy maturation via negative regulation of Rab7 expression

“…For HBV, Sir D et al first reported that HBV could activate the early autophagic pathway (7). But it seems like autophagy causes no harm to HBV (8). The precise underlying mechanisms why the enhanced autophagosomes promote HBV DNA replication instead of engulfing it need to be elucidated.…”

Identification of hydrolyzable tannins (punicalagin, punicalin and geraniin) as novel inhibitors of hepatitis B virus covalently closed circular DNA

“…Hydrolyzable tannins are known to be hydrolyzed into smaller polyphenols, such as gallic or ellagic acids, it is therefore conceivable that the inhibition of cccDNA formation and stability by tannin is attributed to different hydrolysis products and/or other metabolites. Gallic or ellagic acids have been shown to inhibit multiple steps in HBV life cycle, including virus entry (Huang et al, 2014), DNA replication (He et al, 2011; Zhong et al, 2015), and HBeAg secretion (Shin et al, 2005). However, the direct effect of hydrolyzable tannins on cccDNA metabolism has not been studied.…”