Animal Models to Study Hepatitis C Virus Infection.

Animal Models to Study Hepatitis C Virus Infection.
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DOI:
10.3389/fimmu.2018.01032
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发表时间:
2018
影响因子:
7.3
通讯作者:
Meuleman P
Meuleman P
中科院分区:
医学2区
文献类型:
--
作者:
Burm R;Collignon L;Mesalam AA;Meuleman P

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丙型肝炎病毒(HCV)是全球主要的健康问题,有超过7100万慢性感染者。虽然新的直接作用的抗病毒药物显着提高了HCV的治愈率,高治疗成本,耐药病毒变异的潜在出现,以及保护性疫苗的不可用性的挑战完全根除HCV。相关的动物模型是必需的,额外的开发仍然是必要的,以有效地研究HCV生物学,病毒-宿主相互作用和新的抗病毒方法和预防性疫苗的评价。黑猩猩是唯一易受实验性HCV感染的非人灵长类动物,已被广泛用于研究HCV感染,特别是用于分析感染后的先天性和适应性免疫应答。然而,财政,实际,特别是道德的限制,促使替代小动物模型的探索。这些包括不同类型的转基因小鼠,免疫缺陷小鼠,其肝脏植入人肝细胞(人源化小鼠),以及最近的免疫活性啮齿动物,其易受与HCV密切相关的病毒感染。在这篇综述中,我们提供了一个概述,目前可用的动物模型,已被证明是有价值的研究丙型肝炎病毒,并讨论其主要优点和缺点。
With more than 71 million chronically infected people, the hepatitis C virus (HCV) is a major global health concern. Although new direct acting antivirals have significantly improved the rate of HCV cure, high therapy cost, potential emergence of drug-resistant viral variants, and unavailability of a protective vaccine represent challenges for complete HCV eradication. Relevant animal models are required, and additional development remains necessary, to effectively study HCV biology, virus–host interactions and for the evaluation of new antiviral approaches and prophylactic vaccines. The chimpanzee, the only non-human primate susceptible to experimental HCV infection, has been used extensively to study HCV infection, particularly to analyze the innate and adaptive immune response upon infection. However, financial, practical, and especially ethical constraints have urged the exploration of alternative small animal models. These include different types of transgenic mice, immunodeficient mice of which the liver is engrafted with human hepatocytes (humanized mice) and, more recently, immunocompetent rodents that are susceptible to infection with viruses that are closely related to HCV. In this review, we provide an overview of the currently available animal models that have proven valuable for the study of HCV, and discuss their main benefits and weaknesses.
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