The hepatitis B virus-trimera mouse: a model for human HBV infection and evaluation of anti-HBV therapeutic agents
Autor: | Oded Jurim, Ido Lubin, Lewis Neville, John Gillard, Eithan Galun, Leonard Yuen, Ofer Ben-Moshe, Ofer Nussbaum, Joseph Arazi, Daniel Shouval, Shlomo Dagan, Tarek S. Mansour, Ahamed Eid, Yair Reisner, Ehud Ilan, Shoshana Berr, Tatjana Burakova, Rachel Eren |
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Rok vydání: | 1999 |
Předmět: |
Hepatitis B virus
medicine.medical_treatment Viremia Mice SCID Liver transplantation medicine.disease_cause Antibodies Viral Kidney Antiviral Agents Deoxycytidine Polymerase Chain Reaction Virus Mice Orthohepadnavirus Mice Inbred NOD medicine Animals Humans RNA Messenger Serum Albumin Hepatitis B Surface Antigens Hepatology biology virus diseases biology.organism_classification medicine.disease Hepatitis B Virology digestive system diseases Liver Transplantation Transplantation Disease Models Animal Hepadnaviridae Liver Lamivudine Immunology DNA Viral Viral load |
Zdroj: | Hepatology (Baltimore, Md.). 29(2) |
ISSN: | 0270-9139 |
Popis: | 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 1 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 beta-L-5-fluoro-2',3'-dideoxycytidine (beta-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. |
Databáze: | OpenAIRE |
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