For the ideal preclinical animal model of hepatitis B virus (HBV), its hepatocytes should allow HBV entry and cccDNA generation and have both innate and adaptive immune systems. However, HBV only naturally infects humans and chimpanzees due to highly restricted species specificity, and no effective model has been established so far to truly reflect the immune mechanism and pathogenesis of HBV infection. This article reviews five commonly used mouse models, i.e., HBV transgenic model, HBV plasmid DNA hydrodynamic injection model, AAV-HBV transfection model, cccDNA surrogate model, and human-mouse chimeric liver model, and looks forward to the new models that will appear in the future, such as hNTCP transgenic cynomolgus monkey, rhesus monkey, or pig models, so as to provide a reference for researchers to select these models, accelerate the process of drug screening, validate new therapies, and better solve the problems of HBV biological pathogenesis.

Animals ; Cell Line ; Cytological Techniques ; methods ; Embryonic Stem Cells ; cytology ; Interleukin Receptor Common gamma Subunit ; genetics ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Mutation