title: Alterations in hepatitis B virus nucleotide sequences in a chronic virus carrier from immunotolerant to immunoactive phase.
abstract: Factors involved in transition from the immunotolerant to immunoactive phase in chronic hepatitis B virus (HBV) infection remain unclear. We investigated viral mutations occurring during transition and elucidated their virological and immunological significance. Full-length HBV DNA sequences were serially determined in a chronic HBV carrier from the immunotolerant to immunoactive phase. Viral replicative competence was examined by transfection analysis. HBV-specific CD8(+) T cell response was evaluated by coculture of CD8(+) T cells with autologous dendritic cells followed by interferon-gamma Elispot assay. Eleven point mutations and two deletions appeared around the onset of the immunoactive phase. Viral replicative competence declined significantly after the onset of active hepatitis. Examination of the CD8(+) T cell response against two putative T-cell epitopes, which contained substituted amino acids from the immunotolerant to immunoactive phase, showed that mutant HBV epitopes gave a lesser T cell response than wild-type HBV ones. In summary, point mutations and deletions may occur prior to or concurrent with the onset of the immunoactive phase during chronic HBV infection. These mutations may result in a significant decrease in both viral replicative competence and HBV-specific CD8(+) T cell response, suggesting a possible adaptation for the maintenance of viral persistence.
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita 565-0871, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ohkawa
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tatsumi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ishida
authors.forename: Matsuo
authors.initials: M
authors.lastname: Deguchi
authors.forename: Masanori
authors.initials: M
authors.lastname: Kagita
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hosui
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyagi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Katayama
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
mesh_terms: D000328:Adult; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002353:Carrier State / Q000276:immunology* / Q000821:virology*; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D017354:Point Mutation; D014779:Virus Replication / Q000235:genetics
chemical_list: D018984:Epitopes, T-Lymphocyte