title: Induction of endoplasmic reticulum-derived oxidative stress by an occult infection related S surface antigen variant.
abstract: OBJECTIVE
  To investigate the mechanism of endoplasmic reticulum (ER) stress induction by an occult infection related hepatitis B virus S surface antigen (HBsAg) variant.
  
  
  METHODS
  We used an HBsAg variant with lower secretion capacity, which was a KD variant from a Korean subject who was occultly infected with the genotype C. We compared the expression profiles of ER stress-related proteins between HuH-7 cells transfected with HBsAg plasmids of a wild-type and a KD variant using Western blot.
  
  
  RESULTS
  Confocal microscopy indicated that the KD variant had higher levels of co-localization with ER than the wild-type HBsAg. The KD variant up-regulated ER stress-related proteins and induced reactive oxygen species (ROS) compared to the wild-type via an increase in calcium. The KD variant also down-regulated anti-oxidant proteins (HO-1, catalase and SOD) compared to the wild-type, which indicates positive amplification loops of the ER-ROS axis. The KD variant also induced apoptotic cell death via the up-regulation of caspase proteins (caspase 6, 9 and 12). Furthermore, the KD variant induced a higher level of nitric oxide than wild-type HBsAg via the up-regulation of the iNOS protein.
  
  
  CONCLUSIONS
  Our data indicate that occult infection related HBsAg variants can lead to ER-derived oxidative stress and liver cell death in HuH-7 cells.
authors.affiliation: In-Kyung Lee, Seoung-Ae Lee, Hong Kim, You-Sub Won, Bum-Joon Kim, Department of Microbiology and Immunology, Liver Research Institute, Cancer Research Institute and SNUMRC, College of Medicine, Seoul National University, Seoul 110-799, South Korea.
authors.forename: In-Kyung
authors.initials: IK
authors.lastname: Lee
authors.affiliation: In-Kyung Lee, Seoung-Ae Lee, Hong Kim, You-Sub Won, Bum-Joon Kim, Department of Microbiology and Immunology, Liver Research Institute, Cancer Research Institute and SNUMRC, College of Medicine, Seoul National University, Seoul 110-799, South Korea.
authors.forename: Seoung-Ae
authors.initials: SA
authors.lastname: Lee
authors.affiliation: In-Kyung Lee, Seoung-Ae Lee, Hong Kim, You-Sub Won, Bum-Joon Kim, Department of Microbiology and Immunology, Liver Research Institute, Cancer Research Institute and SNUMRC, College of Medicine, Seoul National University, Seoul 110-799, South Korea.
authors.forename: Hong
authors.initials: H
authors.lastname: Kim
authors.affiliation: In-Kyung Lee, Seoung-Ae Lee, Hong Kim, You-Sub Won, Bum-Joon Kim, Department of Microbiology and Immunology, Liver Research Institute, Cancer Research Institute and SNUMRC, College of Medicine, Seoul National University, Seoul 110-799, South Korea.
authors.forename: You-Sub
authors.initials: YS
authors.lastname: Won
authors.affiliation: In-Kyung Lee, Seoung-Ae Lee, Hong Kim, You-Sub Won, Bum-Joon Kim, Department of Microbiology and Immunology, Liver Research Institute, Cancer Research Institute and SNUMRC, College of Medicine, Seoul National University, Seoul 110-799, South Korea.
authors.forename: Bum-Joon
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D059865:Endoplasmic Reticulum Stress; D020869:Gene Expression Profiling; D014644:Genetic Variation; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000235:genetics* / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D018613:Microscopy, Confocal; D008875:Middle Aged; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D006514:Hepatitis B Surface Antigens; D017382:Reactive Oxygen Species
keywords: Apoptotic cell death; Colocalization; Endoplasmic reticulum oxidative stress; Hepatitis B virus; KD variant; Reactive oxidative species