title: Interaction of hepatitis C virus core protein with Hsp60 triggers the production of reactive oxygen species and enhances TNF-alpha-mediated apoptosis.
abstract: The hepatitis C virus (HCV) core protein is the primary protein component of the nucleocapsid that encapsidates the viral RNA genome. Besides its role as a viral structural protein, the core protein is implicated in HCV chronic infection-associated liver diseases by induction of reactive oxygen species (ROS) production and modulation of apoptosis. Here, we show that interaction of the core protein, through its N-terminal domain (amino acids 1-75), with heat shock protein (Hsp60) is critical for the induction of ROS production, leading to sensitization of core protein-expressing cells to apoptosis induced by tumor necrosis factor-alpha (TNF-alpha). Moreover, overexpression of Hsp60 rescued the core protein-expressing cells from cell death by reducing ROS production. Collectively, our results suggest that impairment of Hsp60 function through binding of HCV core protein contributes to HCV viral pathogenesis by ROS generation and amplification of the apoptotic effect of TNF-alpha.
authors.affiliation: Department of Biotechnology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, South Korea.
authors.forename: Su-Min
authors.initials: SM
authors.lastname: Kang
authors.forename: Sung-Jun
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Wooseong
authors.initials: W
authors.lastname: Lee
authors.forename: Geon-Woo
authors.initials: GW
authors.lastname: Kim
authors.forename: Kee-Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Kang-Yell
authors.initials: KY
authors.lastname: Choi
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Oh
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D018834:Chaperonin 60 / Q000378:metabolism*; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014758:Viral Core Proteins / Q000502:physiology*
chemical_list: D018834:Chaperonin 60; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus