Journal article
Hepatitis C Virus Triggers Apoptosis of a Newly Developed Hepatoma Cell Line Through Antiviral Defense System
Gastroenterology (New York, N.Y. 1943), Vol.133(5), pp.1649-1659
11/2007
DOI: 10.1053/j.gastro.2007.09.017
PMID: 17983809
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.
Details
- Title: Subtitle
- Hepatitis C Virus Triggers Apoptosis of a Newly Developed Hepatoma Cell Line Through Antiviral Defense System
- Creators
- Haizhen Zhu - Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida, USAHuijia Dong - Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FloridaErika Eksioglu - University of FloridaAlan Hemming - University of FloridaMengde Cao - University of FloridaJames M. Crawford - University of FloridaDavid R. Nelson - University of FloridaChen Liu - University of Florida
- Resource Type
- Journal article
- Publication Details
- Gastroenterology (New York, N.Y. 1943), Vol.133(5), pp.1649-1659
- Publisher
- Elsevier Inc
- DOI
- 10.1053/j.gastro.2007.09.017
- PMID
- 17983809
- ISSN
- 0016-5085
- eISSN
- 1528-0012
- Language
- English
- Date published
- 11/2007
- Academic Unit
- Surgery
- Record Identifier
- 9984322939702771
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