Small animal model systems for studying hepatitis B virus replication and pathogenesis

The lack of reliable in vitro infection systems and convenient animal models has hindered progress in hepatitis B virus (HBV) research and the development of new treatment options. Due to various restraints encountered using chimpanzees and other models of HBV infection that are based on HBV-related viruses, and due to the necessity to work with small and well-characterized animal systems, it is not surprising that most recent developments have focused on mice. Various strains of transgenic mice harboring the entire HBV genome, or selected viral genes, were developed and proved to be very useful to elucidate mechanisms of HBV replication and pathogenesis. Furthermore, novel, exciting alternative mouse models have been developed recently, which allow not only studies on viral replication, but also the investigation of mechanisms of viral entry and clearance. This article provides an overview and discussion of the different mouse models of HBV replication and infection that are currently available.