Association of the Hepatitis B Virus Large Surface Protein with Viral Infectivity and Endoplasmic Reticulum Stress-mediated Liver Carcinogenesis

doi:10.3390/cells9092052

CNU IR > Pharmacy and Science > Dept. of Biotechnology (including master's program) > Periodical Articles > Item 310902800/34082

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Title:	Association of the Hepatitis B Virus Large Surface Protein with Viral Infectivity and Endoplasmic Reticulum Stress-mediated Liver Carcinogenesis
Authors:	Lin, Wei-Ling Hung, Jui-Hsiang Huang, Wenya
Contributors:	Natl Cheng Kung Univ Hosp, Dept Pathol, Lab Clin Biochem Chia Nan Univ Pharm & Sci, Dept Biotechnol Natl Cheng Kung Univ, Coll Med, Dept Med Lab Sci & Biotechnol
Keywords:	hepatitis B virus large surface protein endoplasmic reticulum viral entry sodium taurocholate cotransporting polypeptide ground glass hepatocyte pre-S deletion hepatocellular carcinoma
Date:	2020
Issue Date:	2022-11-18 11:23:10 (UTC+8)
Publisher:	Mdpi
Abstract:	Hepatitis B is the most prevalent viral hepatitis worldwide, affecting approximately one-third of the world's population. Among HBV factors, the surface protein is the most sensitive biomarker for viral infection, given that it is expressed at high levels in all viral infection phases. The large HBV surface protein (LHBs) contains the integral pre-S1 domain, which binds to the HBV receptor sodium taurocholate co transporting polypeptide on the hepatocyte to facilitate viral entry. The accumulation of viral LHBs and its prevalent pre-S mutants in chronic HBV carriers triggers a sustained endoplasmic reticulum (ER) overload response, leading to ER stress-mediated cell proliferation, metabolic switching and genomic instability, which are associated with pro-oncogenic effects. Ground glass hepatocytes identified in HBV-related hepatocellular carcinoma (HCC) patients harbor pre-S deletion variants that largely accumulate in the ER lumen due to mutation-induced protein misfolding and are associated with increased risks of cancer recurrence and metastasis. Moreover, in contrast to the major HBs, which is decreased in tumors to a greater extent than it is in peritumorous regions, LHBs is continuously expressed during tumorigenesis, indicating that LHBs serves as a promising biomarker for HCC in people with CHB. Continuing efforts to delineate the molecular mechanisms by which LHBs regulates pathological changes in CHB patients are important for establishing a correlation between LHBs biomarkers and HCC development.
Relation:	Cells, v.9, n.9, pp.16
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Periodical Articles

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