Hepatitis C virus triggers apoptosis of a newly developed hepatoma cell line through antiviral defense system
Hepatitis C virus triggers apoptosis of a newly developed hepatoma cell line through antiviral defense system
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DOI：
10.1053/j.gastro.2007.09.017
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发表时间：
2007-11-01
期刊：
影响因子：
29.4
通讯作者：
Liu, Chen
中科院分区：
文献类型：
--
作者：
Zhu, Haizhen;Dong, Huijia;Liu, Chen
背景与目的：丙型肝炎病毒（HepatitisCvirus，HCV）是一种可引起慢性病毒感染的病毒.病毒对宿主免疫系统的逃避在HCV的发病机制中起着关键作用。然而，HCV和肝细胞先天抗病毒防御系统之间的相互作用尚不清楚。本研究的目的是研究人肝细胞对HCV感染的反应。方法：我们从分化良好的肝细胞癌组织中建立了一种新的人肝癌细胞系LH 86。感染性HCV分离株JFH-1用于感染LH 86细胞。检测病毒感染后HCV的复制和细胞凋亡。HCV诱导的细胞凋亡的机制进行了确定。检测I型干扰素诱导和相关信号分子。结果：LH 86细胞可感染JFH-1 HCV。病毒感染导致大量细胞凋亡。细胞凋亡与病毒复制有关，因为用抗CD 81阻断病毒进入或用干扰素抑制病毒复制保护细胞免受HCV诱导的细胞凋亡。HCV诱导的细胞凋亡似乎是由肿瘤坏死因子相关凋亡诱导配体（TRAIL）及其受体死亡受体4和死亡受体5触发的，它们在HCV感染中上调。HCV还激活干扰素应答因子3，其诱导干扰素和TRAIL在LH 86细胞中的表达。结论：我们的研究表明，一个特定的HCV分离株，JFH-1，是在这个新的肝癌细胞系的细胞病变。LH 86细胞通过诱导干扰素和触发感染细胞的凋亡来建立完整的先天性抗病毒防御。这项研究揭示了宿主肝细胞对急性HCV感染的一种新机制。
Background & Aims: Hepatitis C virus (HCV) has a tendency to cause chronic viral infection. Viral evasion of host immune systems plays a key role in the pathogenesis of HCV. However, the interaction between HCV and hepatocyte innate antiviral defense systems is not understood. The aim of this study was to examine how human hepatocytes respond to HCV infection. Methods: We have established a novel human hepatoma cell line, LH86, from a well-differentiated hepatocellular carcinoma tissue. An infectious HCV isolate, JFH-1, was used to infect LH86 cells. HCV replication and apoptosis after viral infection were examined. Mechanisms of HCV-induced apoptosis were determined. Type I interferon induction and the relevant signaling molecules were examined. Results: LH86 cells permitted JFH-1 HCV infection. The viral infection caused massive apoptosis. The apoptosis was related to viral replication, because blocking viral entry with anti-CD81 or suppressing viral replication with interferon protected cells from HCV-induced apoptosis. The HCV-induced apoptosis appeared to be triggered by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors, death receptor 4 and death receptor 5, which were up-regulated in HCV infection. HCV also activated interferon response factor 3, which induced expression of interferon and TRAIL in LH86 cells. Conclusions: Our study showed that a specific HCV isolate, JFH-1, is cytopathic in this new hepatoma cell line. LH86 cells mount an intact innate antiviral defense through induction of interferon and triggering apoptosis of infected cells. This study reveals a novel mechanism by which host hepatocytes respond to acute HCV infection.