TY - JOUR
T1 - The hepatitis B virus-trimera mouse
T2 - A model for human HBV infection and evaluation of anti-HBV therapeutic agents
AU - Ilan, Ehud
AU - Burakova, Tatjana
AU - Dagan, Shlomo
AU - Nussaum, Ofer
AU - Lubin, Ido
AU - Eren, Rachel
AU - Ben-Moshe, Ofer
AU - Arazi, Joseph
AU - Berr, Shoshana
AU - Neville, Lewis
AU - Yuen, Leonard
AU - Mansour, Tarek S.
AU - Gillard, John
AU - Eid, Ahamed
AU - Jurim, Oded
AU - Shouval, Daniel
AU - Reisner, Yair
AU - Galun, Eithan
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033030127&partnerID=8YFLogxK
U2 - 10.1002/hep.510290228
DO - 10.1002/hep.510290228
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C2 - 9918935
AN - SCOPUS:0033030127
SN - 0270-9139
VL - 29
SP - 553
EP - 562
JO - Hepatology
JF - Hepatology
IS - 2
ER -
