Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Front Immunol. 2021 Feb 19;12:638447. doi: 10.3389/fimmu.2021.638447. eCollection 2021.
Viral hepatitis particularly Hepatitis B Virus (HBV) is still an ongoing health issue worldwide. Despite the vast technological advancements in research and development, only HBV vaccines, typically given during early years, are currently available as a preventive measure against acquiring the disease from a secondary source. In general, HBV can be cleared naturally by the human immune system if detected at low levels early. However, long term circulation of HBV in the peripheral blood may be detrimental to the human liver, specifically targeting human hepatocytes for cccDNA integration which inevitably supports HBV life cycle for the purpose of reinfection in healthy cells. Although there is some success in using nucleoside analogs or polyclonal antibodies targeting HBV surface antigens (HBsAg) in patients with acute or chronic HBV (CHB), majority of them would either respond only partially or succumb to the disease entirely unless they undergo liver transplants from a fully matched healthy donor and even so may not necessarily guarantee a 100% chance of survival. Indeed, cultures and various transgenic animal models have already provided us with a good understanding of HBV but they primarily lack human specificity or virus-host interactions in the presence of human immune surveillance. Therefore, the demand of utilizing humanized mice has increased over the last decade as a pre-clinical platform for investigating human-specific immune responses against HBV as well as identifying potential immunotherapeutic strategies in eradicating the virus. Basically, this review covers some of the recent developments and key advantages of humanized mouse models over other conventional transgenic mice platforms.
病毒性肝炎，尤其是乙型肝炎病毒（HBV），仍然是全球范围内持续存在的健康问题。尽管在研究和开发方面取得了巨大的技术进步，但目前仅可获得 HBV 疫苗作为预防措施，用于防止从二次来源感染该疾病。通常情况下，如果在早期检测到低水平的 HBV，人体免疫系统可以自然清除它。然而，HBV 在周围血液中的长期循环可能对人类肝脏有害，特别是针对人类肝细胞进行 cccDNA 整合，这不可避免地支持 HBV 的生命周期，以便在健康细胞中再次感染。尽管在急性或慢性乙型肝炎（CHB）患者中使用核苷类似物或针对 HBV 表面抗原（HBsAg）的多克隆抗体取得了一定的成功，但大多数患者要么只能部分应答，要么完全无法抵御该疾病，除非他们接受来自完全匹配的健康供体的肝移植，即使这样也不一定能保证 100%的生存机会。事实上，培养物和各种转基因动物模型已经为我们提供了对 HBV 的很好理解，但它们主要缺乏人类特异性或病毒-宿主相互作用，而人类免疫监测则存在这些作用。因此，在过去十年中，利用人源化小鼠作为研究针对 HBV 的人类特异性免疫反应以及确定消除病毒的潜在免疫治疗策略的临床前平台的需求有所增加。总的来说，本综述涵盖了人源化小鼠模型相对于其他传统转基因小鼠平台的一些最新进展和关键优势。
