title: A Novel Hydrodynamic Injection Mouse Model of HBV Genotype C for the Study of HBV Biology and the Anti-Viral Activity of Lamivudine.
abstract: BACKGROUND
  Absence of an immunocompetent mouse model of persistent hepatitis B virus (HBV) infection has hindered the research of HBV infection and the development of antiviral medications.
  
  
  OBJECTIVE
  In the present study, we aimed to develop a novel HBV genotype C mouse model by hydrodynamic injection (HI) and then used it to evaluate the antiviral activity of lamivudine.
  
  
  METHODS
  A quantity of 15 μg of HBV plasmid [pcDNA3.1 (+)-HBV1.3C], adeno-associated virus-HBV1.3C (pAAV-HBV1.3C) or pAAV-HBV1.2A) were injected into male C57BL/6 mice, by HI, accounting for a total of 13 mice per group. Then, lamivudine was administered to mice with sustained HBV viremia, for 4 weeks. Real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry methods were used to detect HBsAg, HBeAg, HBsAb, HBcAg and HBV DNA, in serum or liver of the mice, at indicated time points.
  
  
  RESULTS
  In 60% of the mice injected with pcDNA3.1 (+)-HBV1.3C, HBsAg, HBeAg, HBcAg and HBV DNA persisted for > 20 weeks in liver, post-injection, with no HBsAb appearance. Meanwhile, no significant inflammation was observed in these mice. Compared with pAAV-HBV1.2A and pAAV-HBV1.3C, pcDNA3.1 (+)-HBV1.3C administration led to higher and longer HBV viremia. Furthermore, serum HBV DNA was significantly reduced by lamivudine, after 4 weeks administration, and returned to the original level, after ceasing administration for 1 week, in the mice.
  
  
  CONCLUSIONS
  In conclusion, our observations indicated that pcDNA3.1 (+)-HBV1.3C was superior to AAV/HBV plasmid for establishment of persistent HBV infection by HI, in vivo, and this mouse model could be useful for studies of hepatitis virology and for the development of innovatory treatments for HBV infections.
authors.affiliation: Liver Disease Key Lab, 458 Hospital of PLA, Guangzhou, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Li
authors.affiliation: Liver Disease Key Lab, 458 Hospital of PLA, Guangzhou, China.
authors.forename: Guangze
authors.initials: G
authors.lastname: Liu
authors.affiliation: Liver Disease Key Lab, 458 Hospital of PLA, Guangzhou, China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Chen
authors.affiliation: Liver Disease Key Lab, 458 Hospital of PLA, Guangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Liver Disease Key Lab, 458 Hospital of PLA, Guangzhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Liver Disease Key Lab, 458 Hospital of PLA, Guangzhou, China.
authors.forename: Xiangping
authors.initials: X
authors.lastname: Kong
keywords: Animal; Hepatitis B virus; Injections; Intravenous; Lamivudine; Models