A transgenic mouse lineage useful for testing antivirals targeting hepatitis B virus

To test therapeutics for the efficacy against hepatitis B virus (HBV), the lineage of transgenic mice serum HBV DNA of levels of 106 to 108 viral genome equivalents/ml is made. In the study described in this chapter, mice from the lineage, producing the highest levels of HBV markers were developed. Endogenous DNA polymerase activity was present in the particles pelleted from serum and the product of this reaction migrated in agarose gels, indicating whole virus in the mouse serum. HBV core antigen was detected by immunohistochemistry. The antigen found in the nuclei of the exocrine pancreatic cells of mice and pancreatic islet cells were stained frequently. HBV surface antigen was detected in the cytoplasm of a minority of hepatocytes. After a two-week follow-up, the viral DNA levels of vehicle- and lamivudine-treated mice increased to 27 and 17% of pretreatment levels, while those of the entecavir-treated mice remained at 1% of pretreatment levels. These results indicate that this model system can be used to evaluate the efficacy of inhibitors of viral DNA replication.