Hepatitis C virus core protein potentiates TNF-alpha-induced NF-kappaB activation through TRAF2-IKKbeta-dependent pathway

Biochem Biophys Res Commun. 2001 Jun 1;284(1):15-9. doi: 10.1006/bbrc.2001.4936.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • Cell Line
  • Drug Synergism
  • Gene Expression / drug effects
  • Humans
  • I-kappa B Kinase
  • Macromolecular Substances
  • NF-kappa B / metabolism*
  • Protein Binding / drug effects
  • Protein Serine-Threonine Kinases / metabolism*
  • Proteins / genetics
  • Proteins / metabolism*
  • Proteins / pharmacology
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor, Type I
  • Signal Transduction / drug effects
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • Transfection
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Viral Core Proteins / biosynthesis
  • Viral Core Proteins / genetics
  • Viral Core Proteins / pharmacology*

Substances

  • Antigens, CD
  • Macromolecular Substances
  • NF-kappa B
  • Proteins
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • Tumor Necrosis Factor-alpha
  • Viral Core Proteins
  • nucleocapsid protein, Hepatitis C virus
  • Protein Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human