title: [Study on the differences of two mouse models of hepatitis B virus infection by transduction with rAAV8-1. 3HBV].
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.
authors.affiliation: Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Dong
authors.forename: Wen-Hong
authors.initials: WH
authors.lastname: Tian
authors.forename: Chi-Jie
authors.initials: CJ
authors.lastname: Yu
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Guo-Jing
authors.initials: GJ
authors.lastname: Wang
authors.forename: Guo-Chao
authors.initials: GC
authors.lastname: Wei
authors.forename: Yu-Sen
authors.initials: YS
authors.lastname: Zhou
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Wu
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006509:Hepatitis B / Q000276:immunology / Q000821:virology*; D006510:Hepatitis B Antibodies / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D022781:Hepatocytes / Q000276:immunology / Q000821:virology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014161:Transduction, Genetic; D014779:Virus Replication
chemical_list: D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens