Hepatitis B virus core antigen determines viral persistence in a C57BL/6 mouse model
Journal
Proceedings of the National Academy of Sciences of the United States of America
Journal Volume
107
Journal Issue
20
Pages
9340-9345
Date Issued
2010
Author(s)
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-γ 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.
SDGs
Other Subjects
gamma interferon; hepatitis B core antigen; hepatitis B surface antigen; hepatitis B virus X protein; hepatitis B(e) antigen; virus DNA; animal cell; animal experiment; animal model; animal tissue; antibody titer; antigen expression; article; C57BL 6 mouse; codon; controlled study; deletion mutant; gene construct; hepatitis B; Hepatitis B virus; humoral immunity; male; mouse; nonhuman; open reading frame; persistent virus infection; plasmid; priority journal; spleen cell; virion; virus core; virus mutant; virus replication; virus transcription; Hepatitis B virus; Mus
Publisher
National Academy of Sciences
Type
journal article