Human liver chimeric mice provide a model for hepatitis B and C virus infection and treatment
Human liver chimeric mice provide a model for hepatitis B and C virus infection and treatment
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DOI：
10.1172/jci40094
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发表时间：
2010-03-01
影响因子：
15.9
通讯作者：
Verma, Inder M.
中科院分区：
文献类型：
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作者：
Bissig, Karl-Dimiter;Wieland, Stefan F.;Verma, Inder M.
乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）感染的通用小动物模型的缺乏已经成为进一步了解病毒生物学和测试抗病毒治疗的障碍。我们最近描述了一种可调节的系统，用于重新填充免疫缺陷小鼠的肝脏（特别是缺乏富马奈尔的小鼠）。乙酰乙酸水解酶[Fah]，重组激活基因2 [Rag2]，以及IL-2受体的γ链[Il-2r γ])与人肝细胞的关系。在这里，我们已经证明，高移植剂量(3 × 10（6)至5 × 10(6)个人肝细胞/小鼠）比以前在这些小鼠中获得的肝嵌合率更高，高达95%的人肝细胞嵌合。高水平的老鼠。乙肝病毒和丙型肝炎病毒在人肝脏嵌合中同时繁殖，感染丙型肝炎病毒的小鼠对抗病毒治疗有反应。这种人类肝脏嵌合小鼠模型将扩大研究HBV和HCV感染以及可能的其他人类嗜肝性病原体的实验可能性，并证明对抗病毒药物测试有用。
A paucity of versatile small animal models of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection has been an impediment to both furthering understanding of virus biology and testing antiviral therapies. We recently described a regulatable system for repopulating the liver of immunodeficient mice (specifically mice lacking fumaryl. acetoacetate hydrolase [Fah], recombination activating gene 2 [Rag2], and the gamma-chain of the receptor for IL-2 [Il-2r gamma]) with human hepatocytes. Here we have shown that a high transplantation dose (3 x 10(6) to 5 x 10(6) human hepatocytes/mouse) generates a higher rate of liver chimerism than was previously obtained in these mice, up to 95% human-hepatocyte chimerism. Mice with a high level. of human liver chimerism propagated both HBV and HCV, and the HCV-infected mice were responsive to antiviral treatment. This human liver chimeric mouse model will expand the experimental possibilities for studying HBV and HCV infection, and possibly other human hepatotropic pathogens, and prove useful for antiviral drug testing.