[Study on the differences of two mouse models of hepatitis B virus infection by transduction with rAAV8-1. 3HBV].

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 4×109(Viral genome,vg),4×1010vg and 4×1011vg 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 4×1011vg,over 40% of hepatocytes expressed HBcAg and serum viral DNA reached over 105IU/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 4×1011vg 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 4×1010vg.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 4×109~4×1011vg 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.