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 journalArticle

34 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

Fingerprint

Reactive Oxygen Species
Tumor Necrosis Factor-alpha
Apoptosis
Hepacivirus
Proteins
Viral Structural Proteins
Nucleocapsid Proteins
Viral Genome
Viral RNA
Virus Diseases
Heat-Shock Proteins
Liver Diseases
Cell Death
Amino Acids
Hepatitis C virus nucleocapsid protein

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kang, Su Min ; Kim, Sung Jun ; Kim, Jung Hee ; Lee, Wooseong ; Kim, Geon Woo ; Lee, Kee Ho ; Choi, Kang-Yell ; Oh, Jong-Won. / Interaction of hepatitis C virus core protein with Hsp60 triggers the production of reactive oxygen species and enhances TNF-α-mediated apoptosis. In: Cancer Letters. 2009 ; Vol. 279, No. 2. pp. 230-237.
@article{8c1572e5e13c4a0194b2b3e8b3cedc5f,
title = "Interaction of hepatitis C virus core protein with Hsp60 triggers the production of reactive oxygen species and enhances TNF-α-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-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.",
author = "Kang, {Su Min} and Kim, {Sung Jun} and Kim, {Jung Hee} and Wooseong Lee and Kim, {Geon Woo} and Lee, {Kee Ho} and Kang-Yell Choi and Jong-Won Oh",
year = "2009",
month = "7",
day = "8",
doi = "10.1016/j.canlet.2009.02.003",
language = "English",
volume = "279",
pages = "230--237",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

Interaction of hepatitis C virus core protein with Hsp60 triggers the production of reactive oxygen species and enhances TNF-α-mediated apoptosis. / Kang, Su Min; Kim, Sung Jun; Kim, Jung Hee; Lee, Wooseong; Kim, Geon Woo; Lee, Kee Ho; Choi, Kang-Yell; Oh, Jong-Won.

In: Cancer Letters, Vol. 279, No. 2, 08.07.2009, p. 230-237.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Interaction of hepatitis C virus core protein with Hsp60 triggers the production of reactive oxygen species and enhances TNF-α-mediated apoptosis

AU - Kang, Su Min

AU - Kim, Sung Jun

AU - Kim, Jung Hee

AU - Lee, Wooseong

AU - Kim, Geon Woo

AU - Lee, Kee Ho

AU - Choi, Kang-Yell

AU - Oh, Jong-Won

PY - 2009/7/8

Y1 - 2009/7/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=67349125450&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349125450&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2009.02.003

DO - 10.1016/j.canlet.2009.02.003

M3 - Article

C2 - 19264393

AN - SCOPUS:67349125450

VL - 279

SP - 230

EP - 237

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

IS - 2

ER -