title: The L60V variation in hepatitis B virus core protein elicits new epitope-specific cytotoxic T lymphocytes and enhances viral replication.
abstract: Mutations in the core protein (HBc) of hepatitis B virus (HBV) are associated with aggressive hepatitis and advanced liver diseases in chronic hepatitis B (CHB). In this study, we identified the L60V variation in HBc that generates a new HLA-A2-restricted CD8(+) T cell epitope by screening an overlapping 9-mer peptide pool covering HBc and its variants. The nonameric epitope V60 was determined by structural and immunogenic analysis. The HBc L60V variation is correlated with hepatic necroinflammation and higher viral levels, and it may be associated with a poor prognosis in CHB patients. Immunization with the defined HBV epitope V60 peptide elicited specific cytotoxic T lymphocyte (CTL)-induced liver injury in HLA-A2(+) HBV transgenic mice. In addition, in vitro and in vivo experiments both demonstrated that the HBc L60V variation facilitates viral capsid assembly and increases HBV replication. These data suggest that the HBc L60V variation can impact both HBV replication and HBV-specific T cell responses. Therefore, our work provides further dissection of the impact of the HBc L60V variation, which orchestrates HBV replication, viral persistence, and immunopathogenesis during chronic viral infection.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yulin
authors.initials: Y
authors.lastname: Ren
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Bao
authors.initials: B
authors.lastname: Zhao
authors.forename: Lipeng
authors.initials: L
authors.lastname: Qiu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.forename: Dongping
authors.initials: D
authors.lastname: Xu
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.forename: Songdong
authors.initials: S
authors.lastname: Meng
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D002213:Capsid / Q000502:physiology*; D045744:Cell Line, Tumor; D002681:China; D003461:Crystallography; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D057809:HEK293 Cells; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D020125:Mutation, Missense / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication / Q000235:genetics*
chemical_list: D018984:Epitopes, T-Lymphocyte; D014758:Viral Core Proteins