Abstract
Previous work has implicated that the core protein of hepatitis C virus (HCV) may play a modulatory effect on NF-kappaB activation induced by TNF-alpha. However, it is unclear how HCV core protein modulates TNF-alpha-induced NK-kappaB activation. Here we show that overexpression of HCV core protein potentiates NF-kappaB activation induced by TNF-alpha. Expression of dominant negative form of TRAF2 inhibits the synergistic effects of HCV core protein on NF-kappaB activation, suggesting that HCV core protein potentiates NF-kappaB activation through TRAF2. Moreover, we demonstrate that HCV core protein potentiates TRAF2-mediated NF-kappaB activation via IKKbeta. In addition, HCV core protein associates with TNF-R1-TRADD-TRAF2 signaling complex, resulting in synergistically activation of NF-kappaB induced by TNF-alpha. Thus, these observations indicate that HCV core protein may play an important role in the regulation of the cellular inflammatory and immune responses through NF-kappaB.
Copyright 2001 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / metabolism
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Cell Line
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Drug Synergism
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Gene Expression / drug effects
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Humans
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I-kappa B Kinase
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Macromolecular Substances
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NF-kappa B / metabolism*
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Protein Binding / drug effects
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Protein Serine-Threonine Kinases / metabolism*
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Proteins / genetics
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Proteins / metabolism*
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Proteins / pharmacology
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Receptors, Tumor Necrosis Factor / metabolism
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Receptors, Tumor Necrosis Factor, Type I
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Signal Transduction / drug effects
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TNF Receptor-Associated Factor 1
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TNF Receptor-Associated Factor 2
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Transfection
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Tumor Necrosis Factor-alpha / pharmacology*
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Viral Core Proteins / biosynthesis
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Viral Core Proteins / genetics
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Viral Core Proteins / pharmacology*
Substances
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Antigens, CD
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Macromolecular Substances
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NF-kappa B
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Proteins
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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TNF Receptor-Associated Factor 1
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TNF Receptor-Associated Factor 2
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Tumor Necrosis Factor-alpha
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Viral Core Proteins
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nucleocapsid protein, Hepatitis C virus
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Protein Serine-Threonine Kinases
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CHUK protein, human
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I-kappa B Kinase
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IKBKB protein, human
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IKBKE protein, human