Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Innate Immunity Unit, Institut Pasteur.
Curr Opin HIV AIDS. 2020 May;15(3):173-179. doi: 10.1097/COH.0000000000000616.
Antiviral therapy for chronic hepatitis B infection is rarely curative, thus research in HBV cure strategies is a priority. Drug development and testing has been hampered by the lack of robust cell culture systems and small animal models. This review summarizes existing models for HBV cure research and focuses on recent developments since 2017 until today.
The field has progressed in the development of cell culture and animal models to study HBV. Although early cell culture systems relied on transfection of HBV genomes in hepatoma cell lines, novel models expressing the entry receptor for HBV are susceptible to infection. Improved culture conditions for primary human hepatocytes, the primary target of HBV, have enabled the screening and validation of novel antivirals. Mouse models grafted with partially humanized livers are suitable for testing viral entry inhibitors or direct acting antivirals, and can be reconstituted with human immune cells to analyze immunotherapies. Other immunocompetent models include mice transduced with HBV genomes or woodchucks infected with their native hepatitis virus.
Model systems for HBV research have helped lay the groundwork for the development and optimization of antiviral and immune-based therapeutic approaches that are now moving to clinical trials.
慢性乙型肝炎病毒感染的抗病毒治疗很少能根治，因此，HBV 根治策略的研究是当务之急。药物研发和测试受到缺乏稳健的细胞培养系统和小动物模型的阻碍。本文综述了现有的 HBV 根治研究模型，并重点介绍了 2017 年以来的最新进展。
该领域在研究 HBV 的细胞培养和动物模型方面取得了进展。虽然早期的细胞培养系统依赖于在肝癌细胞系中转染 HBV 基因组，但表达 HBV 进入受体的新型模型容易受到感染。对原代人肝细胞（HBV 的主要靶标）的培养条件进行了改进，从而能够筛选和验证新型抗病毒药物。部分人源化肝脏移植的小鼠模型适合测试病毒进入抑制剂或直接作用抗病毒药物，并且可以用人类免疫细胞重建来分析免疫疗法。其他免疫功能健全的模型包括转导 HBV 基因组的小鼠或感染其天然肝炎病毒的土拨鼠。
HBV 研究的模型系统为开发和优化抗病毒和免疫为基础的治疗方法奠定了基础，这些方法现在正在进入临床试验。
