{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T08:47:50Z","timestamp":1783759670414,"version":"3.55.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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 acute liver failure via suppression of AKT prosurviving activity, suggesting that interventions directed at enhancing the activation or functional activity of AKT may be of therapeutic value in Fas-mediated progressive liver cell injury and liver diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1800732","type":"journal-article","created":{"date-parts":[[2018,8,31]],"date-time":"2018-08-31T13:29:24Z","timestamp":1535722164000},"page":"2303-2314","source":"Crossref","is-referenced-by-count":29,"title":["Hepatitis B Virus Surface Antigen Enhances the Sensitivity of Hepatocytes to Fas-Mediated Apoptosis via Suppression of AKT Phosphorylation"],"prefix":"10.1093","volume":"201","author":[{"given":"Zhen-Tang","family":"Jing","sequence":"first","affiliation":[{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University , Fuzhou 350122 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7118-815X","authenticated-orcid":false,"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University , Fuzhou 350122 ,","place":["China"]},{"name":"Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University , Fuzhou 350004 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Xiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University , Fuzhou 350122 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University , Fuzhou 350122 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Ting","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University , Fuzhou 350122 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Nan","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University , Fuzhou 350122 ,","place":["China"]},{"name":"Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University , Fuzhou 350004 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Jian","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University , Fuzhou 350122 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University , Fuzhou 350122 ,","place":["China"]},{"name":"Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University , Fuzhou 350004 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,10,15]]},"reference":[{"key":"2025030417573734200_r1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0092-8674(00)81874-7","article-title":"Apoptosis by death factor","volume":"88","author":"Nagata","year":"1997","journal-title":"Cell"},{"key":"2025030417573734200_r2","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/nm0497-409","article-title":"Essential roles of the Fas ligand in the development of hepatitis","volume":"3","author":"Kondo","year":"1997","journal-title":"Nat. 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Chem."},{"key":"2025030417573734200_r18","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1128\/MCB.22.1.207-220.2002","article-title":"Molecular ordering of the initial signaling events of CD95","volume":"22","author":"Algeciras-Schimnich","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"2025030417573734200_r19","doi-asserted-by":"crossref","first-page":"27316","DOI":"10.1016\/S0021-9258(19)61513-9","article-title":"CD95-mediated apoptosis in vivo involves acid sphingomyelinase","volume":"275","author":"Kirschnek","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2025030417573734200_r20","doi-asserted-by":"crossref","first-page":"22307","DOI":"10.1074\/jbc.272.35.22307","article-title":"Activation-induced aggregation and processing of the human Fas antigen. Detection with cytoplasmic domain-specific antibodies","volume":"272","author":"Kamitani","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2025030417573734200_r21","doi-asserted-by":"crossref","first-page":"38241","DOI":"10.1074\/jbc.274.53.38241","article-title":"Identification and characterization of a ligand-independent oligomerization domain in the extracellular region of the CD95 death receptor","volume":"274","author":"Papoff","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2025030417573734200_r22","first-page":"5659","article-title":"Cutting edge: SDS-stable Fas microaggregates: an early event of Fas activation occurring with agonistic anti-Fas antibody but not with Fas ligand","volume-title":"J. 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Pathol."},{"key":"2025030417573734200_r31","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/sj.cdd.4401549","article-title":"Akt inhibition upregulates FasL, downregulates c-FLIPs and induces caspase-8-dependent cell death in Jurkat T lymphocytes","volume":"12","author":"Uriarte","year":"2005","journal-title":"Cell Death Differ."},{"key":"2025030417573734200_r32","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1097\/01.LAB.0000079328.76631.28","article-title":"Cellular FLICE\/caspase-8-inhibitory protein as a principal regulator of cell death and survival in human hepatocellular carcinoma","volume":"83","author":"Okano","year":"2003","journal-title":"Lab. Invest."},{"key":"2025030417573734200_r33","doi-asserted-by":"crossref","first-page":"6319","DOI":"10.1128\/JVI.02627-10","article-title":"Subversion of cellular autophagy machinery by hepatitis B virus for viral envelopment","volume":"85","author":"Li","year":"2011","journal-title":"J. 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Microbiol."},{"key":"2025030417573734200_r39","doi-asserted-by":"crossref","first-page":"e6132","DOI":"10.5812\/hepatmon.6132","article-title":"The role of Fas\/Fas ligand system in the pathogenesis of liver cirrhosis and hepatocellular carcinoma","volume":"12","author":"Hammam","year":"2012","journal-title":"Hepat. Mon."},{"key":"2025030417573734200_r40","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1084\/jem.182.5.1223","article-title":"Involvement of the CD95 (APO-1\/Fas) receptor and ligand in liver damage","volume":"182","author":"Galle","year":"1995","journal-title":"J. Exp. Med."},{"key":"2025030417573734200_r41","first-page":"429","article-title":"Fas antigen expression and its relationship with apoptosis in human hepatocellular carcinoma and noncancerous tissues","volume":"149","author":"Higaki","year":"1996","journal-title":"Am. J. Pathol."},{"key":"2025030417573734200_r42","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/ijc.23921","article-title":"EGF and HGF levels are increased during active HBV infection and enhance survival signaling through extracellular matrix interactions in primary human hepatocytes","volume":"124","author":"Barreiros","year":"2009","journal-title":"Int. J. Cancer"},{"key":"2025030417573734200_r43","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1046\/j.1365-2893.1999.00175.x","article-title":"Involvement of Fas system-mediated apoptosis in pathogenesis of viral hepatitis","volume":"6","author":"Hayashi","year":"1999","journal-title":"J. Viral Hepat."},{"key":"2025030417573734200_r44","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1093\/emboj\/16.10.2794","article-title":"FLICE is activated by association with the CD95 death-inducing signaling complex (DISC)","volume":"16","author":"Medema","year":"1997","journal-title":"EMBO J."},{"key":"2025030417573734200_r45","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1007\/s10495-015-1104-6","article-title":"Lipid rafts and raft-mediated supramolecular entities in the regulation of CD95 death receptor apoptotic signaling","volume":"20","author":"Gajate","year":"2015","journal-title":"Apoptosis"},{"key":"2025030417573734200_r46","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/ni1024","article-title":"Ligand-independent redistribution of Fas (CD95) into lipid rafts mediates clonotypic T cell death","volume":"5","author":"Muppidi","year":"2004","journal-title":"Nat. Immunol."},{"key":"2025030417573734200_r47","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1158\/1541-7786.MCR-07-0331","article-title":"Localization of Fas\/CD95 into the lipid rafts on down-modulation of the phosphatidylinositol 3-kinase signaling pathway","volume":"6","author":"B\u00e9n\u00e9teau","year":"2008","journal-title":"Mol. Cancer Res."},{"key":"2025030417573734200_r48","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1083\/jcb.118.6.1305","article-title":"Hepatitis B surface antigen assembles in a post-ER, pre-Golgi compartment","volume":"118","author":"Huovila","year":"1992","journal-title":"J. Cell Biol."},{"key":"2025030417573734200_r49","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1172\/JCI26373","article-title":"Endoplasmic reticulum stress: cell life and death decisions","volume":"115","author":"Xu","year":"2005","journal-title":"J. Clin. 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