Viral Hepatitis
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2005; 11(41): 6433-6439
Published online Nov 7, 2005. doi: 10.3748/wjg.v11.i41.6433
Hepatitis C virus non-structural 5A protein can enhance full-length core protein-induced nuclear factor-κB activation
Qing-Jiao Liao, Lin-Bai Ye, Khalid Amine Timani, Ying-Long She, Xiao-Jun Yang, Li Ye, Zheng-Hui Wu
Qing-Jiao Liao, Khalid Amine Timani, Ying-Long She, Xiao-Jun Yang, Li Ye, Zheng-Hui Wu, Lin-Bµgai Ye, State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, Hubei Province, China
Author contributions: All authors contributed equally to the work.
Supported by the Ph D Program Foundation of Ministry of Education of China, No. 20010486015
Correspondence to: Lin-Bai Ye, Dr., Professor, State Key Laboratory of Virology, College of Life Science, Wuhan University, Wuhan 430072, Hubei Province, China. linbaiye@whu.edu.cn
Telephone: +86-27-68752372 Fax: +86-27-68752372
Received: March 13, 2005
Revised: April 26, 2005
Accepted: April 30, 2005
Published online: November 7, 2005
Abstract

AIM: To study the effects of hepatitis C virus (HCV) core and non-structural 5A (NS5A) proteins on nuclear factor-κB (NF-κB) activity for understanding their biological function on chronic hepatitis caused by HCV infection.

METHODS: Luciferase assay was used to measure the activity of NF-κB in three different cell lines cotransfected with a series of deletion mutants of core protein alone or together with NS5A protein using pNF-κB-Luc as a reporter plasmid. Western blot and indirect immunofluorescence assays were used to confirm the expression of proteins and to detect their subcellular localization, respectively. Furthermore, Western blot was also used to detect the expression levels of NF-κB/p65, NF-κB/p50, and inhibitor κB-a (IκB-a).

RESULTS: The wild-type core protein (C191) and its mutant segments (C173 and C158) could activate NF-κB in Huh7 cells only and activation caused by (C191) could be enhanced by NS5A protein. Moreover, the full-length core protein and its different deletion mutants alone or together with NS5A protein did not enhance the expression level of NF-κB. The NF-κB activity was augmented due to the dissociation of NF-κB-IκB complex and the degradation of IκB-a.

CONCLUSION: NF-κB is the key transcription factor that can activate many genes that are involved in the cellular immune response and inflammation. Coexpression of the full-length core protein along with NS5A can enhance the NF-κB activation, and this activation may play a significant role in chronic liver diseases including hepatocellular carcinoma associated with HCV infection.

Keywords: HCV; NS5A; Core protein; NF-κB