title: Upregulation of endoplasmic reticulum stress and reactive oxygen species by naturally occurring mutations in hepatitis B virus core antigen.
abstract: Hepatitis B virus (HBV) infection is associated with a broad spectrum of clinical manifestations, including cirrhosis and hepatocellular carcinoma (HCC). Endoplasmic reticulum (ER) stress and subsequent oxidative stress have been implicated in liver carcinogenesis and disease progression with chronic inflammation. In our previous study, several mutations in the precore/core region of HBV genotype C were identified from 70 Korean chronic patients, and the mutations were associated with HCC and/or HBV e antigen serostatus. Here, we found that the naturally occurring mutations P5T/H/L of the HBV core antigen induced ER stress. The upregulation of ER stress resulted in higher reactive oxygen species production, intracellular calcium concentration, inflammatory cytokines as well as surface antigen production and apoptosis of cells. This study suggested that these mutations may contribute to the progression of liver disease in chronic patients.
authors.affiliation: 1Department of Biomedical Sciences, Microbiology and Immunology, Liver Research Institute, and Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: HyunJoo
authors.initials: H
authors.lastname: Lee
authors.affiliation: 1Department of Biomedical Sciences, Microbiology and Immunology, Liver Research Institute, and Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Hong
authors.initials: H
authors.lastname: Kim
authors.affiliation: 1Department of Biomedical Sciences, Microbiology and Immunology, Liver Research Institute, and Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Seoung-Ae
authors.initials: SA
authors.lastname: Lee
authors.affiliation: 1Department of Biomedical Sciences, Microbiology and Immunology, Liver Research Institute, and Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: You-Sub
authors.initials: YS
authors.lastname: Won
authors.affiliation: 2Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Korea.
authors.forename: Hye-In
authors.initials: HI
authors.lastname: Kim
authors.affiliation: 2Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Korea.
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Inn
authors.affiliation: 1Department of Biomedical Sciences, Microbiology and Immunology, Liver Research Institute, and Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Bum-Joon
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D017209:Apoptosis; D059865:Endoplasmic Reticulum Stress; D005838:Genotype; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D017382:Reactive Oxygen Species / Q000378:metabolism*; D056910:Republic of Korea
chemical_list: D006512:Hepatitis B Core Antigens; D050505:Mutant Proteins; D017382:Reactive Oxygen Species