HBV multidrug resistant sW172* truncated variant possibly involve in the ER stress pathway during hepatocarcinogenesis

We investigated the biological effect of HBV rtA181T/sW172* point mutation on HBsAg secretion and the potential mechanisms involved in hepatocarcinogenesis. Plasmids expressed full-long HBV wildtype and HBV rtA181T/sW172* were transfected into HepG2 HCC cell lines or were injected to C57BL / 6 mice. The HBsAg and HBeAg expressions of extracellular and intracellular proteins, mice serum and liver tissues were detected by ELISA. The localization of truncate protein was characterized in vitro. The expression of ER stress gene GRP78 mRNA was determined. Significant high levels of HBsAg was observed in supernatants of cells transfected with HBV wildtype or serum of mice injected with HBV wt compared with HBV rtA181T/sW172* mutant. Reverse trend was observed in intracellular cells and intrahepatic liver cells. S wild protein only could rescue this dysfunction. HBV rtA181T/sW172* truncate surface proteins showed a more aggregated cytoplasmic pattern which also localized to the ER in comparison with HBV wt. Meanwhile, grp78 mRNA was increased in cells 72 hour post-transfected with HBV rtA181T/sW172* cells relative to HBV wt (P=0.0154). The HBV sW172* truncate mutant has a defect on HBsAg secretion which can lead to surface protein retention in ER, it may contribute to the hepatocarcinogenisis through activating the ER stress signaling pathways.PubMe