The hepatitis B virus-trimera mouse: A model for human HBV infection and evaluation of anti-HBV therapeutic agents

Ehud Ilan, Tatjana Burakova, Shlomo Dagan*, Ofer Nussaum, Ido Lubin, Rachel Eren, Ofer Ben-Moshe, Joseph Arazi, Shoshana Berr, Lewis Neville, Leonard Yuen, Tarek S. Mansour, John Gillard, Ahamed Eid, Oded Jurim, Daniel Shouval, Yair Reisner, Eithan Galun

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

Previous studies have demonstrated the feasibility of implantation of human blood cells or tissues in lethally irradiated mice or rats, radioprotected with SCID mouse bone marrow cells: The Trimera system. In the present study, we describe the development of a mouse Trimera model for human hepatitis B virus (HBV) infection. In this model, viremia is induced by transplantation of ex vivo HBV-infected human liver fragments. Engraftment of the human liver fragments, evaluated by hematoxylin-eosin staining and human serum albumin mRNA expression, was observed in 85% of the transplanted animals I month postimplantation. Viremia levels were determined in these mice by measuring serum HBV DNA using polymerase chain reaction (PCR), followed by dot-blot hybridization. HBV DNA is first detected 8 days after liver transplantation. Viremia attains a peak between days 18 and 25 when HBV infection is observed in 85% of the transplanted animals. The HBV-Trimera model was used to evaluate the therapeutic effects of human polyclonal anti- HBs antibodies (Hepatect) and of two reverse-transcriptase inhibitors, lamivudine (3TC) and β-L-5-fluoro-2',3'-dideoxycytidine (β-L-5FddC). Treatment of HBV-Trimera mice with these drugs effectively reduced both the percentage of infected animals and the viral load in their sera. Treatment cessation resulted in rebound of viral load, indicating HBV replication upon drug withdrawal. These results show that the HBV-Trimera model represents a novel experimental tool for simulating human HBV infection and evaluating potential anti-HBV therapeutic agents.

Original languageAmerican English
Pages (from-to)553-562
Number of pages10
JournalHepatology
Volume29
Issue number2
DOIs
StatePublished - 1999
Externally publishedYes

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