Animal Models for the Study of Hepatitis C Virus Infection and Related Liver Disease
Animal Models for the Study of Hepatitis C Virus Infection and Related Liver Disease
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DOI：
10.1053/j.gastro.2012.02.016
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发表时间：
2012-05-01
期刊：
影响因子：
29.4
通讯作者：
Bukh, Jens
中科院分区：
文献类型：
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作者：
Bukh, Jens
丙型肝炎病毒（HCV）每年导致超过30万人的肝脏相关死亡。尽管引入了直接作用的抗病毒药物，但慢性HCV患者的治疗仍不理想。目前还没有预防HCV感染的疫苗。相关的动物模型对HCV的研究和药物、疫苗的开发具有重要意义。黑猩猩是研究HCV感染和相关先天性和适应性宿主免疫反应的最佳模型。它们可用于HCV疫苗的免疫原性和有效性研究。HCV感染的唯一小动物模型是T细胞和B细胞缺陷小鼠与人类嵌合肝脏。虽然这些小鼠不能用于适应性免疫的研究，但它们为HCV中和，病毒与受体之间的相互作用，先天宿主反应和治疗方法提供了新的见解。最近在开发基因人源化小鼠方面的进展令人兴奋，但这些模型仅允许研究HCV生命周期中的特定步骤，并且具有有限的病毒复制或没有病毒复制。
Hepatitis C virus (HCV) causes liver-related death in more than 300,000 people annually. Treatments for patients with chronic HCV are suboptimal, despite the introduction of directly acting antiviral agents. There is no vaccine that prevents HCV infection. Relevant animal models are important for HCV research and development of drugs and vaccines. Chimpanzees are the best model for studies of HCV infection and related innate and adaptive host immune responses. They can be used in immunogenicity and efficacy studies of HCV vaccines. The only small animal models of robust HCV infection are T- and B-cell deficient mice with human chimeric livers. Although these mice cannot be used in studies of adaptive immunity, they have provided new insights into HCV neutralization, interactions between virus and receptors, innate host responses, and therapeutic approaches. Recent progress in developing genetically humanized mice is exciting, but these models only permit studies of specific steps in the HCV life cycle and have limited or no viral replication.