Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin, China.
Peking Union Medical College Hospital, Chinese Medical Academy, Beijing, China.
Hepatology. 2017 Oct;66(4):1045-1057. doi: 10.1002/hep.29211. Epub 2017 Aug 26.
The development of pathogenic mechanisms, specific antiviral treatments and preventive vaccines for hepatitis C virus (HCV) infection has been limited due to lack of cell culture models that can naturally imitate the entire HCV life cycle. Here, we established an HCV cell culture model based on human fetal liver stem cells (hFLSCs) that supports the entire blood-borne hepatitis C virus (bbHCV) life cycle. More than 90% of cells remained infected by various genotypes. bbHCV was efficiently propagated, and progeny virus were infectious to hFLSCs. The virus could be passed efficiently between cells. The viral infectivity was partially blocked by specific antibodies or small interfering RNA against HCV entry factors, whereas HCV replication was inhibited by antiviral drugs. We observed viral particles of approximately 55 nm in diameter in both cell culture media and infected cells after bbHCV infection.
Our data show that the entire bbHCV life cycle could be naturally imitated in hFLSCs. This model is expected to provide a powerful tool for exploring the process and the mechanism of bbHCV infection at the cellular level and for evaluating the treatment and preventive strategies of bbHCV infection. (Hepatology 2017;66:1045-1057).
由于缺乏能够自然模拟整个丙型肝炎病毒（HCV）生命周期的细胞培养模型，因此对 HCV 感染的致病机制、特异性抗病毒治疗和预防性疫苗的开发受到限制。在这里，我们基于人胎肝干细胞（hFLSCs）建立了一种支持整个血源 HCV（bbHCV）生命周期的 HCV 细胞培养模型。超过 90%的细胞仍然被各种基因型感染。bbHCV 能够高效增殖，并且衍生的病毒能够感染 hFLSCs。病毒能够在细胞间有效传递。针对 HCV 进入因子的特异性抗体或小干扰 RNA 部分阻断了病毒的感染力，而抗病毒药物则抑制了 HCV 复制。在 bbHCV 感染后，我们在细胞培养物和感染细胞中观察到直径约为 55nm 的病毒颗粒。
我们的数据表明，整个 bbHCV 生命周期可以在 hFLSCs 中自然模拟。该模型有望为探索 bbHCV 感染的细胞水平过程和机制以及评估 bbHCV 感染的治疗和预防策略提供有力工具。（《肝脏病学》2017 年；66：1045-1057）
