KMID : 0921620180480030093
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Journal of Bacteriology and Virology 2018 Volume.48 No. 3 p.93 ~ p.101
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IKK¥ã Facilitates the Activation of NF-¥êB by Hepatitis C Virus Core Protein
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Kang Bo-Yeong
Lee So-Yeong Kim Jin-Ik Choi Hye-Jung Joo Woo-Hong Kim Dong-Wan
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Abstract
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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 ¥êB (NF-¥êB) 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-¥êB pathway, and the mechanism by which the core protein affects NF-¥êB activity remains nuclear. In this study, the functional interaction of HCV core protein and I¥êB kinase ¥ã (IKK¥ã) was investigated using the expression plasmids of core and the components of IKK complex. The data revealed that HCV core protein activates NF-¥êB. Also, HCV core protein up-regulated the phosphorylation and degradation of I¥êB¥á. The activating effect of HCV core protein on NF-¥êB was synergistically elevated by IKK¥ã. It was noticed that the N-terminal IKK¥â binding site, C-terminal leucine zipper, and zinc finger domains of IKK¥ã are not necessary for its synergistic effect. HCV core protein and IKK¥ã appeared to activate NF-¥êB by up-regulating the IKK¥â activity resulting in the degradation of I¥êB¥á. As expected, HCV core protein induced the expression of NF-¥êB-targeted pro-inflammatory genes such as iNOS, IL-1¥â and IL-6 in the transcription level. These results suggest that HCV core protein induces NF-¥êB through the interaction with IKK¥ã and may play a critical role in the development of inflammation and related liver diseases.
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KEYWORD
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Hepatitis C virus, Core protein, NF-¥êB, IKK¥ã, Inflammation
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