The use of the hydrodynamic HBV animal model to study HBV biology and anti-viral therapy

Mali Ketzinel-Gilad*, Arie Zauberman, Ofer Nussbaum, Yariv Shoshany, Ofer Ben-Moshe, Orit Pappo, Yaakov Felig, Ehud Ilan, Hanna Wald, Shlomo Dagan, Eithan Galun

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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-Ab17XTL and HBV-Ab19XTL, 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.

Original languageEnglish
Pages (from-to)228-237
Number of pages10
JournalHepatology Research
Volume34
Issue number4
DOIs
StatePublished - Apr 2006
Externally publishedYes

Bibliographical note

Funding Information:
The study was supported by a grant from XTL Biopharmaceuticals Ltd., the Israeli Ministry of Science and by the Horwitz, Blum and Grinspoon Foundation.

Keywords

  • Animal models
  • Hepatitis B virus infection
  • Hydrodynamic injection
  • Naked DNA
  • Transgenic mice

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