Hepatitis B virus core antigen determines viral persistence in a C57BL/6 mouse model.
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.
Lin
Yi-Jiun
YJ
Graduate Institute of Microbiology, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
Huang
Li-Rung
LR
Yang
Hung-Chih
HC
Tzeng
Horng-Tay
HT
Hsu
Ping-Ning
PN
Wu
Hui-Lin
HL
Chen
Pei-Jer
PJ
Chen
Ding-Shinn
DS
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*
D006512:Hepatitis B Core Antigens; D007371:Interferon-gamma