The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chou, A.-H.
Right arrow Articles by Hsu, P.-N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chou, A.-H.
Right arrow Articles by Hsu, P.-N.
Right arrowPubmed/NCBI databases
*Protein
*Compound via MeSH
*Substance via MeSH
The Journal of Immunology, 2005, 174: 2160-2166.
Copyright © 2005 by The American Association of Immunologists

Hepatitis C Virus Core Protein Modulates TRAIL-Mediated Apoptosis by Enhancing Bid Cleavage and Activation of Mitochondria Apoptosis Signaling Pathway1

Ai-Hsiang Chou*, Hwei-Fang Tsai*,{dagger}, Yi-Ying Wu*, Chung-Yi Hu*, Lih-Hwa Hwang{ddagger}, Ping-I. Hsu and Ping-Ning Hsu2,*,§

* Graduate Institute of Immunology, College of Medicine, National Taiwan University, {dagger} Department of Internal Medicine, Taipei Ho-Ping Municipal Hospital, and {ddagger} Hepatitis Research Center and § Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; and Department of Internal Medicine, Veterans General Hospital-Kaohsiung, Kaohsiung, Taiwan

Hepatitis C virus (HCV) is a major human pathogen causing chronic liver disease, which leads to cirrhosis of liver and hepatocellular carcinoma. The HCV core protein, a viral nucleocapsid, has been shown to affect various intracellular events, including cell proliferation and apoptosis. However, the precise mechanisms of the effects are not fully understood. In this study, we show that HCV core protein sensitizes human hepatocellular carcinoma cell line, Huh7, conferred sensitivity to TRAIL-, but not Fas ligand-mediated apoptosis. Huh7 cells are resistant to TRAIL, despite the induction of caspase-8 after TRAIL engagement. However, HCV core protein induces TRAIL apoptosis signaling via sequential induction of caspase-8, Bid cleavage, activation of mitochondrial pathway, and effector caspase-3. HCV core protein also induces activation of caspase-9 after TRAIL engagement, and the induction of TRAIL sensitivity by HCV core protein could be reversed by caspase-9 inhibitor. Therefore, the HCV core protein-induced TRAIL-mediated apoptosis is dependent upon activation of caspase-8 downstream pathway to convey the death signal to mitochondria, leading to activation of mitochondrial signaling pathway and breaking the apoptosis resistance. These results combined indicate that the HCV core protein enhances TRAIL-, but not Fas ligand-mediated apoptotic cell death in Huh7 cells via a mechanism dependent on the activation of mitochondria apoptosis signaling pathway. These results suggest that HCV core protein may have a role in immune-mediated liver cell injury by modulation of TRAIL-induced apoptosis.




This article has been cited by other articles:


Home page
 J. Virol.Home page
N. K. Mohd-Ismail, L. Deng, S. K. Sukumaran, V. C. Yu, H. Hotta, and Y.-J. Tan
The Hepatitis C Virus Core Protein Contains a BH3 Domain That Regulates Apoptosis through Specific Interaction with Human Mcl-1
J. Virol., October 1, 2009; 83(19): 9993 - 10006.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
L. Deng, T. Adachi, K. Kitayama, Y. Bungyoku, S. Kitazawa, S. Ishido, I. Shoji, and H. Hotta
Hepatitis C Virus Infection Induces Apoptosis through a Bax-Triggered, Mitochondrion-Mediated, Caspase 3-Dependent Pathway
J. Virol., November 1, 2008; 82(21): 10375 - 10385.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. Lan, S. Gorke, S. J. Rau, M. B. Zeisel, E. Hildt, K. Himmelsbach, M. Carvajal-Yepes, R. Huber, T. Wakita, A. Schmitt-Graeff, et al.
Hepatitis C Virus Infection Sensitizes Human Hepatocytes to TRAIL-Induced Apoptosis in a Caspase 9-Dependent Manner
J. Immunol., October 1, 2008; 181(7): 4926 - 4935.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
N. Gasper-Smith, D. M. Crossman, J. F. Whitesides, N. Mensali, J. S. Ottinger, S. G. Plonk, M. A. Moody, G. Ferrari, K. J. Weinhold, S. E. Miller, et al.
Induction of Plasma (TRAIL), TNFR-2, Fas Ligand, and Plasma Microparticles after Human Immunodeficiency Virus Type 1 (HIV-1) Transmission: Implications for HIV-1 Vaccine Design
J. Virol., August 1, 2008; 82(15): 7700 - 7710.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
H. Malhi, F. J Barreyro, H. Isomoto, S. F Bronk, and G. J Gores
Free fatty acids sensitise hepatocytes to TRAIL mediated cytotoxicity
Gut, August 1, 2007; 56(8): 1124 - 1131.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
Y. Li, D. F. Boehning, T. Qian, V. L. Popov, and S. A. Weinman
Hepatitis C virus core protein increases mitochondrial ROS production by stimulation of Ca2+ uniporter activity
FASEB J, August 1, 2007; 21(10): 2474 - 2485.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R.-I. You, M.-C. Chen, H.-W. Wang, Y.-C. Chou, C.-H. Lin, and S.-L. Hsieh
Inhibition of Lymphotoxin-{beta} Receptor-Mediated Cell Death by Survivin-{Delta}Ex3.
Cancer Res., March 15, 2006; 66(6): 3051 - 3061.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. H. Lee, Y. K. Kim, C. S. Kim, S. K. Seol, J. Kim, S. Cho, Y. L. Song, R. Bartenschlager, and S. K. Jang
E2 of Hepatitis C Virus Inhibits Apoptosis
J. Immunol., December 15, 2005; 175(12): 8226 - 8235.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2005 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2005 by The American Association of Immunologists, Inc. All rights reserved.