Interaction of hepatitis C virus core protein with Hsp60 triggers the production of reactive oxygen species and enhances TNF-α-mediated apoptosis

Su Min Kang, Sung Jun Kim, Jung Hee Kim, Wooseong Lee, Geon Woo Kim, Kee Ho Lee, Kang Yell Choi, Jong Won Oh

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

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-α (TNF-α). 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-α.

Original languageEnglish
Pages (from-to)230-237
Number of pages8
JournalCancer Letters
Volume279
Issue number2
DOIs
Publication statusPublished - 2009 Jul 8

Bibliographical note

Funding Information:
We thank Dr. Yasuo Tanaka for providing the HA-tagged Hsp60-expression vector. This work was supported by Korea Research Foundation Grants KRF 2005-C00347 and KRF-2004-005-C00148. S.J.K. was the recipient of a postdoctoral fellowship from the BK21 program of the Korea Ministry of Education and Human Resources Development. J.H.K. was supported in part by the BK21 Program.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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