Interaction of hepatitis C virus core protein with Hsp60 triggers the production of reactive oxygen species and enhances TNF-alpha-mediated apoptosis.
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.
Kang
Su-Min
SM
Department of Biotechnology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, South Korea.
Kim
Sung-Jun
SJ
Kim
Jung-Hee
JH
Lee
Wooseong
W
Kim
Geon-Woo
GW
Lee
Kee-Ho
KH
Choi
Kang-Yell
KY
Oh
Jong-Won
JW
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*
D018834:Chaperonin 60; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus