4K7F

Newly identified epitope V60 from HBV core protein complexed with HLA-A*0201

Summary for 4K7F

• Entry DOI: 10.2210/pdb4k7f/pdb
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, Core protein, ... (4 entities in total)
• Functional Keywords: host-virus interaction, immune response, disease mutation, viral replication, ig-like domain, immune system, tcr, membrane glycoprotein, viral capsid protein
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01892; Secreted: P61769
• Total number of polymer chains: 6
• Total formula weight: 89595.67

Authors

Meng, S.D.,Zhang, Y.,Wu, Y.,Qi, J.X. (deposition date: 2013-04-17, release date: 2013-06-05, Last modification date: 2022-08-24)

Primary citation

Zhang, Y.,Ren, Y.,Wu, Y.,Zhao, B.,Qiu, L.,Li, X.,Xu, D.,Liu, J.,Gao, G.F.,Meng, S.
The L60V variation in hepatitis B virus core protein elicits new epitope-specific cytotoxic T lymphocytes and enhances viral replication.
J.Virol., 87:8075-8084, 2013

PubMed 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.

PubMed: 23678186
DOI: 10.1128/JVI.00577-13

Experimental method

X-RAY DIFFRACTION (2 Å)