Guévin Carl, Lamarre Alain, Labonté Patrick
Institut National de la Recherche Scientifique-Institut Armand-Frappier (INRS-IAF), 531 blvd. Des Prairies, Laval, Québec, Canada.
Antiviral Res. 2009 Oct;84(1):14-22. doi: 10.1016/j.antiviral.2009.07.009. Epub 2009 Jul 19.
In the absence of an immunocompetent mouse model for HCV replication, we developed a convenient xenograft mouse model that produces infectious viral particles. For this purpose, HCV-permissive tumors were generated in SCID/beige mice using a tumorigenic population of the human hepatocarcinoma-derived Huh7 cell line. Following infection, HCV RNA increased in the mouse sera and the human tumor by up to 10(5)GE/ml and 10(7)GE/microg of RNA, respectively. Immunohistochemistry analysis revealed that active viral replication had taken place within the tumor. Moreover, virus recovered from infected mice sera was readily infectious in cell culture. Finally, we showed that interferon-alpha and the protease inhibitor BILN-2061 inhibited the cell culture HCVcc strain JFH1 replication in vivo. In conclusion, we developed a simple and inexpensive mouse model that allows the production of infectious HCV particles in vivo. Such a model will be an extremely valuable tool for the characterization of promising drug candidates.
由于缺乏用于丙型肝炎病毒（HCV）复制的具有免疫活性的小鼠模型，我们开发了一种能产生传染性病毒颗粒的便捷异种移植小鼠模型。为此，使用源自人肝癌的Huh7细胞系的致瘤群体在SCID/米色小鼠中生成了对HCV敏感的肿瘤。感染后，小鼠血清和人肿瘤中的HCV RNA分别增加至高达10⁵基因组当量（GE）/毫升和10⁷GE/微克RNA。免疫组织化学分析显示肿瘤内发生了活跃的病毒复制。此外，从感染小鼠血清中回收的病毒在细胞培养中易于感染。最后，我们表明α干扰素和蛋白酶抑制剂BILN-2061在体内抑制了细胞培养的HCVcc毒株JFH1的复制。总之，我们开发了一种简单且廉价的小鼠模型，该模型能够在体内产生传染性HCV颗粒。这样的模型将是用于鉴定有前景的候选药物的极其有价值的工具。
