IKKγ Facilitates the Activation of NF-κB by Hepatitis C Virus Core Protein

• Published in: Journal of bacteriology and virology Vol. 48; no. 3; pp. 93 - 101
• Main Authors: Kang, Bo Yeong, Lee, So Yeong, Kim, Jin Ik, Choi, Hye Jung, Joo, Woo Hong, Kim, Dong Wan
• Format: Journal Article
• Language: Korean
• Published: 대한미생물학회 2018
• Subjects: 생물학; IKKγ; NF-κB; Inflammation; Core protein; Hepatitis C virus
• ISSN: 1598-2467; 2093-0429
• DOI: 10.4167/jbv.2018.48.3.93

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 I κB 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. KCI Citation Count: 0