Permissiveness of human hepatoma cell lines for HCV infection.
Permissiveness of human hepatoma cell lines for HCV infection.
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DOI：
10.1186/1743-422x-9-30
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发表时间：
2012-01-24
期刊：
影响因子：
4.8
通讯作者：
Uprichard SL
中科院分区：
文献类型：
--
作者：
Sainz B Jr;Barretto N;Yu X;Corcoran P;Uprichard SL
尽管已经在体外对原代和已建立的人肝癌细胞系的丙型肝炎病毒（HCV）感染进行了评估，但迄今为止仅发现Huh7细胞对感染性HCV高度敏感。由于我们对 HCV 生命周期的理解将受益于其他允许细胞系的识别，因此我们组装了一组肝细胞系和非肝细胞系，并评估了它们支持 HCV 感染的能力。在这里，我们展示了细胞培养源性 HCV (HCVcc) 对人肝癌细胞系 PLC/PRF/5 和 Hep3B 的感染，尽管感染水平低于 Huh7 细胞中所达到的水平。为了更好地了解 PLC 和 Hep3B 细胞对 HCVcc 感染的耐受性降低，我们进行了研究来评估每种细胞系支持病毒生命周期特定步骤（即进入、复制、外出和传播）的能力。我们发现，虽然 HCV 感染的早期事件（即进入加复制起始）在 PLC 和 Hep3B 细胞中累积相当或仅略有减少，但与 Huh7 细胞培养物相比，PLC 和 Hep3B 培养物中病毒生命周期的后期步骤（例如稳态复制、从头病毒产生和/或传播）受到不同程度的损害。有趣的是，我们还观察到病毒感染后 PLC 和 Hep3B 细胞中干扰素刺激的基因（即 ISG56）表达显着且差异上调。我们的结论是，后来在这些细胞系中 HCV 感染过程中观察到的限制可能部分归因于 HCV 诱导的先天信号传导。尽管如此，鉴定出两种能够支持真正的 HCVcc 感染（即使水平降低）的新细胞系，扩大了目前可用于 HCV 体外研究的细胞系库，并应有助于进一步阐明 HCV 生物学和调节 HCV 感染的细胞决定因素。
Although primary and established human hepatoma cell lines have been evaluated for hepatitis C virus (HCV) infection in vitro, thus far only Huh7 cells have been found to be highly permissive for infectious HCV. Since our understanding of the HCV lifecycle would benefit from the identification of additional permissive cell lines, we assembled a panel of hepatic and non-hepatic cell lines and assessed their ability to support HCV infection. Here we show infection of the human hepatoma cell lines PLC/PRF/5 and Hep3B with cell culture-derived HCV (HCVcc), albeit to lower levels than that achieved in Huh7 cells. To better understand the reduced permissiveness of PLC and Hep3B cells for HCVcc infection, we performed studies to evaluate the ability of each cell line to support specific steps of the viral lifecycle (i.e. entry, replication, egress and spread). We found that while the early events in HCV infection (i.e. entry plus replication initiation) are cumulatively equivalent or only marginally reduced in PLC and Hep3B cells, later steps of the viral life cycle such as steady-state replication, de novo virus production and/or spread are impaired to different degrees in PLC and Hep3B cultures compared to Huh7 cell cultures. Interestingly, we also observed that interferon stimulated gene (i.e. ISG56) expression was significantly and differentially up-regulated in PLC and Hep3B cells following viral infection. We conclude that the restrictions observed later during HCV infection in these cell lines could in part be attributed to HCV-induced innate signaling. Nevertheless, the identification of two new cell lines capable of supporting authentic HCVcc infection, even at reduced levels, expands the current repertoire of cell lines amendable for the study of HCV in vitro and should aid in further elucidating HCV biology and the cellular determinants that modulate HCV infection.