RRC ID 50024
Author Marusawa H, Hijikata M, Chiba T, Shimotohno K.
Title Hepatitis C virus core protein inhibits Fas- and tumor necrosis factor alpha-mediated apoptosis via NF-kappaB activation.
Journal J Virol
Abstract The effects of hepatitis C virus (HCV) proteins on anti-Fas (CD95/APO-1) antibody- and tumor necrosis factor alpha (TNF-alpha)-mediated apoptosis in different human cell lines were investigated by magnetic concentration of cells which transiently produced the exogenous protein. HepG2 cells, which produced whole HCV proteins, became resistant to anti-Fas-induced apoptotic cell death. Furthermore, the core protein among HCV proteins had a key role in protecting the various cells from apoptosis mediated by not only anti-Fas but also TNF-alpha. We also found that the core functioned in the activation of nuclear factor kappaB (NF-kappaB) in all cells examined. Deletion analysis of the core revealed that the region required for NF-kappaB activation was closely correlated with that for its antiapoptotic function. In addition, we revealed in some cases that the antiapoptotic effect of the core was restrained by coproduction of the inhibitor of NF-kappaB, IkappaB-alpha protein. These results demonstrated that the core inhibits Fas- and TNF-alpha-mediated apoptotic cell death via a mechanism dependent on the activation of NF-kappaB in particular cell lines.
Volume 73(6)
Pages 4713-20
Published 1999-6-1
DOI 10.1128/JVI.73.6.4713-4720.1999
PMID 10233931
PMC PMC112513
MeSH Apoptosis* Caspase 8 Caspase 9 Caspases / physiology Cell Line Humans NF-kappa B / physiology* Structure-Activity Relationship Transfection Tumor Necrosis Factor-alpha / physiology* Viral Core Proteins / chemistry Viral Core Proteins / physiology* fas Receptor / physiology*
IF 4.501
Times Cited 298
Resource
DNA material pCMV-3010 (RDB02966)