Liver chimeric mice with tupaia hepatocyte transplantation as an animal model for hepatitis B virus infection and antiviral therapy

Abstract

The human liver chimeric mouse is a milestone animal model for hepatitis B virus (HBV) infection. Such mice with primary human hepatocyte (PHH) transplantation are adequate to support chronic HBV infection for several weeks and to evaluate antiviral drugs. However, the drawbacks of PHHs include lack of available donors, poor expansion in vitro and ethical issues that limit the application of human liver chimeric mice, necessitating the search for alternatives. Here, we transplanted primary tupaia hepatocytes (PTHs) into the livers of immunodeficient mice and achieved high liver chimerism within six weeks. These tupaia liver chimeric mice are adequate to support chronic infection of the four common HBV genotypes A, B, C and D for 36weeks, as well as evaluate of antiviral drugs, including hepatitis B immune globulin (HBIG), monoclonal antibody and nucleoside analogues (NAs), for preventative therapy and treatment post infection. In conclusion, the tupaia liver chimeric mouse model provides a convenient, efficient and stable animal model for chronic HBV infection and long-term drug evaluation.