The use of the hydrodynamic HBV animal model to study HBV biology and anti-viral therapy.
A simple reproducible and versatile small animal model for hepatitis B virus (HBV) infection is still unavailable. We have generated a simple transient liver-targeted transgenic mouse. Hydrodynamics tail vein injection of a head-to-tail dimer of adw HBV genome (pHBVadwHTD) into immunocompetent mice generated HBsAg and HBeAg expression in both serum and hepatocytes, followed by seroconversion. The injection of pHBVadwHTD into SCID mice generated prolonged HBsAg and HBeAg antigenemia and HBV viremia. Our results demonstrate that hydrodynamic injection of naked DNA could support the generation of HBV particles. We used this model for the assessment of anti-viral agents. Administration of our human monoclonal antibodies, HBV-Ab17(XTL) and HBV-Ab19(XTL), as well as Lamivudine (3TC) treatment suppressed HBV viremia. The model presented herein supports long and stable expression of HBV and will enable determination of various biological questions related to HBV life cycle, mutants and could enhance the development of anti-viral reagents.
Ketzinel-Gilad
Mali
M
Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, Israel 91120.
Zauberman
Arie
A
Nussbaum
Ofer
O
Shoshany
Yariv
Y
Ben-Moshe
Ofer
O
Pappo
Orit
O
Felig
Yaakov
Y
Ilan
Ehud
E
Wald
Hanna
H
Dagan
Shlomo
S
Galun
Eithan
E