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...
Saved in:
Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 20; pp. 9340 - 9345 |
---|---|
Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
18.05.2010
National Acad Sciences |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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. |
---|---|
Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 Contributed by Ding-Shinn Chen, April 8, 2010 (sent for review November 24, 2009) Author contributions: Y.-J.L., L.-R.H., P.-N.H., P.-J.C., and D.-S.C. designed research; Y.-J.L., L.-R.H., and H.-T.T. performed research; Y.-J.L., L.-R.H., and P.-J.C. analyzed data; and Y.-J.L., L.-R.H., H.-C.Y., H.-L.W., and P.-J.C. wrote the paper. 1Y.-J.L. and L.-R.H. contributed equally to this work. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.1004762107 |