Many cell culture and animal models have been used to study hepatitis B virus (HBV) replication and its effects in the liver; these have facilitated development of strategies to control and clear chronic HBV infection. We discuss the advantages and limitations of systems for studying HBV and developing antiviral agents, along with recent advances. New and improved model systems are needed. Cell culture systems should be convenient, support efficient HBV infection, and reproduce responses of hepatocytes in the human body. We also need animals that are fully permissive to HBV infection, convenient for study, and recapitulate human immune responses to HBV and effects in the liver. High-throughput screening technologies could facilitate drug development based on findings from cell and animal models.
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