Study on the differences of two mouse models of hepatitis B virus infection by transduction with rAAV8-1. 3HBV.
- Author:
Gang WANG
1
;
Xiao-Yan DONG
;
Wen-Hong TIAN
;
Chi-Jie YU
;
Gang ZHENG
;
Jie GAO
;
Guo-Jing WANG
;
Guo-Chao WEI
;
Yu-Sen ZHOU
;
Xiao-Bing WU
Author Information
1. Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Dependovirus;
genetics;
metabolism;
Disease Models, Animal;
Genetic Vectors;
genetics;
metabolism;
Hepatitis B;
immunology;
virology;
Hepatitis B Antibodies;
immunology;
Hepatitis B Surface Antigens;
immunology;
Hepatitis B e Antigens;
immunology;
Hepatitis B virus;
genetics;
immunology;
physiology;
Hepatocytes;
immunology;
virology;
Humans;
Male;
Mice;
Mice, Inbred BALB C;
Mice, Inbred C57BL;
Transduction, Genetic;
Virus Replication
- From:
Chinese Journal of Virology
2012;28(5):541-547
- CountryChina
- Language:Chinese
-
Abstract:
We recently developed a mouse model of hepatitis B virus (HBV) chronic infection by intravenous (i.v.) injection with rAAV8-1. 3HBV to C57BL/6 mice. To define the responses of different mouse strains after injection with rAAV8-1. 3HBV, we intravenously injected rAAV8-1. 3HBV at doses of 4 x10(9) (Viral genome,vg), 4 x 10(10) vg and 4 x 10(11) vg to C57BL/6 and BALB/c mice,respectively, and determined the levels of serum HBV antigen and antibody by ELISA,serum viral DNA by real-time PCR,and HBcAg expression in liver by immunohistochemical staining. For C57BL/6 mouse strain with injection of rAAV8-1. 3HBV at three doses, 100% of the mice carried HBV for more than 8 months. The levels of serum HBsAg and HBeAg, serum viral DNA and HBcAg-positive hepatocytes increased in a rAAV8-1. 3HBV dose-dependent manner. For C57BL/6 mice injected with rAAV8-1. 3HBV at the dose of 4 x 10(11) vg,over 40% of hepatocytes expressed HBcAg and serum viral DNA reached over 10(5) IU/mL. No HBV antibody was detected in sera of C57BL/6 mice. For BALB/c mice with injection of rAAV8-1. 3HBV at three doses, serum HBeAg, serum viral DNA and HBcAg-positive hepatocytes persisted for more than 8 months, but serum HBsAg declined remarkably at 2 weeks after injection. The levels of serum HBeAg and HBcAg-positive hepatocytes in BALB/c mice increased in a rAAV8-1. 3HBV dose-dependent manner. Injection with rAAV8-1. 3HBV at the dose of 4 x 10(11) vg resulted in over 50% of BALB/c mice hepatocytes expressing HBcAg. Serum anti-HBsAg were detected in BALB/c mice with rAAV8-1. 3HBV injection at the dose of 4 x10 (10) vg. In conclusion, both C57BL/6 and BALB/c strains can be developed to chronic HBV infection mouse models by i. v. injection with rAAV8-1. 3HBV at doses of 4 x10(9) - 4 x 10(11) vg and the levels of HBV replication increase in a rAAV8-1. 3HBV dose-dependent manner. In contrast to C57BL/6 strain, the BALB/c mice carry out humoral immunity to HBsAg, but fail to mediate HBV clearance.
