Hepatitis B Virus Surface Antigen Enhances the Sensitivity of Hepatocytes to Fas-Mediated Apoptosis via Suppression of AKT Phosphorylation

The Journal of Immunology : Official Journal of the American Association of Immunologists
Zhen-Tang JingXu Lin

Abstract

The Fas receptor/ligand system plays a prominent role in hepatic apoptosis and hepatocyte death. Although hepatitis B virus (HBV) surface Ag (HBsAg) is the most abundant HBV protein in the liver and peripheral blood of patients with chronic HBV infection, its role in Fas-mediated hepatocyte apoptosis has not been disclosed. In this study, we report that HBsAg sensitizes HepG2 cells to agonistic anti-Fas Ab CH11-induced apoptosis through increasing the formation of SDS-stable Fas aggregation and procaspase-8 cleavage but decreasing both the expression of cellular FLIPL/S and the recruitment of FLIPL/S at the death-inducing signaling complex (DISC). Notably, HBsAg increased endoplasmic reticulum stress and consequently reduced AKT phosphorylation by deactivation of phosphoinositide-dependent kinase-1 (PDPK1) and mechanistic target of rapamycin complex 2 (mTORC2), leading to enhancement of Fas-mediated apoptosis. In a mouse model, expression of HBsAg in mice injected with recombinant adenovirus-associated virus 8 aggravated Jo2-induced acute liver failure, which could be effectively attenuated by the AKT activator SC79. Based on these results, it is concluded that HBsAg predisposes hepatocytes to Fas-mediated apoptosis and mice to...Continue Reading

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Citations

Jan 11, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Zhen-Tang JingXu Lin
May 30, 2019·World Journal of Gastrointestinal Oncology·Hong YangJiu-Mao Lin
Apr 8, 2021·African Journal of Laboratory Medicine·Franklin S Azebaze AgueguiaGeorge Mondinde Ikomey
Aug 17, 2021·Frontiers in Cell and Developmental Biology·Peng AnYongting Luo

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