While the HBV-Tg mice serve an important role in delineating the mechanism of HBV clearance and persistence,[3] the system nonetheless inherits the shortfalls that the

mice produce and express HBV antigens but are congenially tolerant to HBV antigens. To meet the requirement of a mouse model resembling natural chronic HBV infection in human adult, there are several approaches in the development of mouse animal Palbociclib molecular weight model by introducing HBV DNA into the mouse liver. Among them, there are three commonly used ones as hydrodynamic-based transfection of HBV DNA, delivery of adenovirus or adeno-associated viral vectors (AAVs) containing HBV DNA. Here, we describe the recent advance in development of immunocompetent non-Tg mouse models for studying HBV immune responses in this review. These non-Tg mouse animal

models for HBV infection provide new approaches to investigate the mechanisms of HBV clearance PF-01367338 molecular weight and persistence. Hydrodynamic injection is a simple and efficient method to deliver genetic materials into liver in vivo.[6] High level of gene expression in liver is achieved by injection of large volume of DNA solution (7% of body weight) via mice tail vein within 5–8 s. This procedure results in high hydraulic pressure in the inferior vena cava and pushing the DNA into hepatic vein. A sharp increase in venous pressure enlarges the liver fenestrae and enhances the membrane permeability, allowing for fluid extravasation into parenchymal cells.[7, 8] The DNA internalization via this physical process is receptor-independent. Immunocompetent mice receiving replication-competent HBV DNA injection hydrodynamically display acute self-limiting hepatitis buy Paclitaxel with very different rates of clearance, whereas the persistent expressions of HBV antigens are observed in hepatocytes of immunocompromised mice.[9] These results suggest that host immune response against viral transgene products may contribute to viral DNA clearance. Indeed, cellular immune responses are elicited in immune-competent mice receiving hydrodynamically delivery of HBV DNA.[10] The vectors backbone carrying the viral

transgenes seems to be a factor influencing HBV clearance in the in vivo transfection models. It has been demonstrated that excision of covalent linkage of bacteria DNA increases maintenance of the transgenes in mouse liver.[11] It is likely that the sequence in AAV backbone regulates long-term expression of HBV transgenes and leads to persistent HBV surface antigenemia. The genetic background of recipient mice also determines viral clearance.[10] It is well established that HBV-specific cytotoxic T cell response is critical for HBV clearance, and it is plausible that different HBV-cytotoxic T lymphocyte (CTL) response occurs in various mice strains. Among certain mouse strains, persistence of HBV DNA in mice liver is accompanied by few activated intrahepatic cytotoxic T cells.