Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA.
Int J Mol Sci. 2020 May 29;21(11):3869. doi: 10.3390/ijms21113869.
The narrow range of species permissive to infection by hepatitis C virus (HCV) presents a unique challenge to the development of useful animal models for studying HCV, as well as host immune responses and development of chronic infection and disease. Following earlier studies in chimpanzees, several unique approaches have been pursued to develop useful animal models for research while avoiding the important ethical concerns and costs inherent in research with chimpanzees. Genetically related hepatotropic viruses that infect animals are being used as surrogates for HCV in research studies; chimeras of these surrogate viruses harboring specific regions of the HCV genome are being developed to improve their utility for vaccine testing. Concurrently, genetically humanized mice are being developed and continually advanced using human factors known to be involved in virus entry and replication. Further, xenotransplantation of human hepatocytes into mice allows for the direct study of HCV infection in human liver tissue in a small animal model. The current advances in each of these approaches are discussed in the present review.
感染丙型肝炎病毒 (HCV) 的物种范围狭窄,这给研究 HCV 的有用动物模型的发展带来了独特的挑战,也给宿主免疫反应以及慢性感染和疾病的发展带来了挑战。在对黑猩猩进行早期研究之后,人们采取了几种独特的方法来开发有用的动物模型进行研究,同时避免了与黑猩猩研究相关的重要伦理问题和成本。感染动物的具有亲缘关系的嗜肝病毒被用作 HCV 在研究中的替代物;这些替代病毒的嵌合体携带 HCV 基因组的特定区域,正在被开发以提高其在疫苗测试中的效用。同时,具有已知参与病毒进入和复制的人类因素的基因人源化小鼠正在被开发并不断推进。此外,将人肝细胞异种移植到小鼠中可以在小动物模型中直接研究 HCV 感染人类肝脏组织的情况。本综述讨论了这些方法中的每一种方法的最新进展。