The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
J Clin Invest. 2010 Mar;120(3):924-30. doi: 10.1172/JCI40094. Epub 2010 Feb 22.
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-2rgamma]) with human hepatocytes. Here we have shown that a high transplantation dose (3 x 106 to 5 x 106 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.
乙型肝炎病毒 (HBV) 和丙型肝炎病毒 (HCV) 感染的通用小型动物模型稀缺，这一直是阻碍深入了解病毒生物学和测试抗病毒疗法的障碍。我们最近描述了一种可调节的系统，用于用人类肝细胞重新填充免疫缺陷小鼠（特别是缺乏延胡索酰乙酰乙酸水解酶 [Fah]、重组激活基因 2 [Rag2] 和白细胞介素 2 受体γ链 [Il-2rgamma] 的小鼠）的肝脏。在这里，我们表明，高移植剂量（3 x 106 至 5 x 106 个人类肝细胞/只小鼠）比以前在这些小鼠中获得的更高的肝嵌合率，高达 95%的人肝细胞嵌合率。具有高水平人肝嵌合的小鼠可传播 HBV 和 HCV，并且感染 HCV 的小鼠对抗病毒治疗有反应。这种人肝嵌合小鼠模型将扩大研究 HBV 和 HCV 感染的实验可能性，并可能对其他人类嗜肝细胞病原体有用，并且对抗病毒药物测试有用。
