Division of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany.
PLoS Pathog. 2011 Apr;7(4):e1002029. doi: 10.1371/journal.ppat.1002029. Epub 2011 Apr 28.
Hepatitis C virus (HCV) is hepatotropic and only infects humans and chimpanzees. Consequently, an immunocompetent small animal model is lacking. The restricted tropism of HCV likely reflects specific host factor requirements. We investigated if dominant restriction factors expressed in non-liver or non-human cell lines inhibit HCV propagation thus rendering these cells non-permissive. To this end we explored if HCV completes its replication cycle in heterokaryons between human liver cell lines and non-permissive cell lines from human non-liver or mouse liver origin. Despite functional viral pattern recognition pathways and responsiveness to interferon, virus production was observed in all fused cells and was only ablated when cells were treated with exogenous interferon. These results exclude that constitutive or virus-induced expression of dominant restriction factors prevents propagation of HCV in these cell types, which has important implications for HCV tissue and species tropism. In turn, these data strongly advocate transgenic approaches of crucial human HCV cofactors to establish an immunocompetent small animal model.
丙型肝炎病毒（HCV）具有嗜肝性，仅感染人类和黑猩猩。因此，缺乏免疫功能正常的小动物模型。HCV 的限制嗜性可能反映了特定的宿主因子要求。我们研究了非肝脏或非人类细胞系中表达的优势限制因子是否抑制 HCV 的复制，从而使这些细胞成为非允许性的。为此，我们探讨了人类肝细胞系和非允许性细胞系（来自人类非肝脏或小鼠肝脏）之间的异核细胞中是否完成 HCV 的复制周期。尽管存在功能性病毒模式识别途径和对干扰素的反应性，但在所有融合细胞中都观察到了病毒的产生，只有在用外源性干扰素处理细胞时才会被消除。这些结果排除了这些细胞类型中固有或病毒诱导的优势限制因子表达阻止 HCV 的复制，这对 HCV 的组织和物种嗜性具有重要意义。反过来，这些数据强烈主张使用关键的人类 HCV 共因子的转基因方法来建立免疫功能正常的小动物模型。
