title: Hepatitis B virus core antigen determines viral persistence in a C57BL/6 mouse model.
abstract: We recently developed a mouse model of hepatitis B virus (HBV) persistence, in which a single i.v. hydrodynamic injection of HBV DNA to C57BL/6 mice allows HBV replication and induces a partial immune response, so that about 20-30% of the mice carry HBV for more than 6 months. The model was used to identify the viral antigen crucial for HBV persistence. We knocked out individual HBV genes by introducing a premature termination codon to the HBV core, HBeAg, HBx, and polymerase ORFs. The specific-gene-deficient HBV mutants were hydrodynamically injected into mice and the HBV profiles of the mice were monitored. About 90% of the mice that received the HBcAg-mutated HBV plasmid exhibited high levels of hepatitis B surface antigenemia and maintained HBsAg expression for more than 6 months after injection. To map the region of HBcAg essential for viral clearance, we constructed a set of serial HBcAg deletion mutants for hydrodynamic injection. We localized the essential region of HBcAg to the carboxyl terminus, specifically to the 10 terminal amino acids (HBcAg176-185). The majority of mice receiving this HBV mutant DNA did not elicit a proper HBcAg-specific IFN-gamma response and expressed HBV virions for 6 months. These results indicate that the immune response triggered in mice by HBcAg during exposure to HBV is important in determining HBV persistence.
authors.affiliation: Graduate Institute of Microbiology, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Yi-Jiun
authors.initials: YJ
authors.lastname: Lin
authors.forename: Li-Rung
authors.initials: LR
authors.lastname: Huang
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Yang
authors.forename: Horng-Tay
authors.initials: HT
authors.lastname: Tzeng
authors.forename: Ping-Ning
authors.initials: PN
authors.lastname: Hsu
authors.forename: Hui-Lin
authors.initials: HL
authors.lastname: Wu
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.forename: Ding-Shinn
authors.initials: DS
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D006509:Hepatitis B / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017384:Sequence Deletion; D014779:Virus Replication / Q000235:genetics / Q000276:immunology*
chemical_list: D006512:Hepatitis B Core Antigens; D007371:Interferon-gamma