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. 2007 Nov;133(5):1649-59.
doi: 10.1053/j.gastro.2007.09.017. Epub 2007 Sep 16.

Hepatitis C virus triggers apoptosis of a newly developed hepatoma cell line through antiviral defense system

Haizhen Zhu  1 , Huijia Dong, Erika Eksioglu, Alan Hemming, Mengde Cao, James M Crawford, David R Nelson, Chen Liu
Affiliations

Hepatitis C virus triggers apoptosis of a newly developed hepatoma cell line through antiviral defense system

Haizhen Zhu et al. Gastroenterology. 2007 Nov.

Abstract

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.

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