Hepatitis C virus infection in phenotypically distinct Huh7 cell lines.

Hepatitis C virus infection in phenotypically distinct Huh7 cell lines.
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DOI:
10.1371/journal.pone.0006561
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发表时间:
2009-08-10
期刊:
影响因子:
3.7
通讯作者:
Uprichard SL
Uprichard SL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sainz B Jr;Barretto N;Uprichard SL

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2005年,基于HCV基因型2a JFH-1分子克隆和人源性肝癌细胞系Huh 7开发了第一个稳健的丙型肝炎病毒(HCV)感染性细胞培养系统。尽管已经做出了很多努力来剖析和扩展JFH-1衍生的克隆的库,但是很少关注宿主细胞,尽管有趣的事实是迄今为止仅发现Huh 7细胞对HCV感染是高度容许的,并且此外仅有限数量的Huh 7细胞系/原种似乎是完全容许的。因此,我们从不同来源编译了一组Huh 7系,并评估了它们对HCV感染的容许性。我们发现,尽管来自不同实验室的Huh 7系在形态和细胞生长方面确实不同,但大多数(9个中的8个)对感染是高度容许的,如感染后的强HCV RNA和从头感染性病毒体产生所证明的。虽然在8个允许细胞系中达到的HCV RNA水平相对相等,但3个Huh 7系显示出更高的感染性病毒体产生,表明这些细胞系更有效地支持病毒生命周期中的复制后事件。与先前的研究一致,发现对感染具有相对抗性的单一Huh 7系证明了HCV进入的阻断。这些研究不仅表明不同实验室中的大多数Huh 7细胞系实际上对HCV感染是高度容许的,而且还鉴定了表型不同的Huh 7细胞系,这可能有助于研究HCV感染的细胞决定因素。
In 2005, the first robust hepatitis C virus (HCV) infectious cell culture system was developed based on the HCV genotype 2a JFH-1 molecular clone and the human-derived hepatoma cell line Huh7. Although much effort has been made to dissect and expand the repertoire of JFH-1-derived clones, less attention has been given to the host cell despite the intriguing facts that thus far only Huh7 cells have been found to be highly permissive for HCV infection and furthermore only a limited number of Huh7 cell lines/stocks appear to be fully permissive. As such, we compiled a panel of Huh7 lines from disparate sources and evaluated their permissiveness for HCV infection. We found that although Huh7 lines from different laboratories do vary in morphology and cell growth, the majority (8 out of 9) were highly permissive for infection, as demonstrated by robust HCV RNA and de novo infectious virion production following infection. While HCV RNA levels achieved in the 8 permissive cell lines were relatively equivalent, three Huh7 lines demonstrated higher infectious virion production suggesting these cell lines more efficiently support post-replication event(s) in the viral life cycle. Consistent with previous studies, the single Huh7 line found to be relatively resistant to infection demonstrated a block in HCV entry. These studies not only suggest that the majority of Huh7 cell lines in different laboratories are in fact highly permissive for HCV infection, but also identify phenotypically distinct Huh7 lines, which may facilitate studies investigating the cellular determinants of HCV infection.
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