IKKγ Facilitates the Activation of NF-κB by Hepatitis C Virus Core Protein.
- Author:
Bo Yeong KANG
1
;
So Yeong LEE
;
Jin Ik KIM
;
Hye Jung CHOI
;
Woo Hong JOO
;
Dong Wan KIM
Author Information
- Publication Type:Original Article
- Keywords: Hepatitis C virus; Core protein; NF-κB; IKKγ; Inflammation
- MeSH: Apoptosis; Binding Sites; Carcinoma, Hepatocellular; Cell Proliferation; Hepacivirus*; Hepatitis C*; Hepatitis*; Hepatitis, Chronic; Inflammation; Interleukin-6; Leucine Zippers; Liver Cirrhosis; Liver Diseases; Phosphorylation; Phosphotransferases; Plasmids; Zinc Fingers
- From:Journal of Bacteriology and Virology 2018;48(3):93-101
- CountryRepublic of Korea
- Language:English
- Abstract: Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV core protein has been shown to modulate various cellular signaling pathways including the nuclear factor κB (NF-κB) pathway which is associated with inflammation, cell proliferation and apoptosis. However, there have been conflicting reports about the effect of HCV core protein on NF-κB pathway, and the mechanism by which the core protein affects NF-κB activity remains nuclear. In this study, the functional interaction of HCV core protein and IκB kinase γ (IKKγ) was investigated using the expression plasmids of core and the components of IKK complex. The data revealed that HCV core protein activates NF-κB. Also, HCV core protein up-regulated the phosphorylation and degradation of IκBα. The activating effect of HCV core protein on NF-κB was synergistically elevated by IKKγ. It was noticed that the N-terminal IKKβ binding site, C-terminal leucine zipper, and zinc finger domains of IKKγ are not necessary for its synergistic effect. HCV core protein and IKKγ appeared to activate NF-κB by up-regulating the IKKβ activity resulting in the degradation of IκBα. As expected, HCV core protein induced the expression of NF-κB-targeted pro-inflammatory genes such as iNOS, IL-1β and IL-6 in the transcription level. These results suggest that HCV core protein induces NF-κB through the interaction with IKKγ and may play a critical role in the development of inflammation and related liver diseases.
