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Journal of Virology, June 1999, p. 4713-4720, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Hepatitis C Virus Core Protein Inhibits Fas- and Tumor Necrosis Factor Alpha-Mediated Apoptosis via NF-kappa B Activation

Hiroyuki Marusawa,1 Makoto Hijikata,2,* Tsutomu Chiba,1 and Kunitada Shimotohno2

Division of Gastroenterology and Hepatology, Department of Medicine, Postgraduate School of Medicine,1 and Laboratory of Human Tumor Viruses, Department of Viral Oncology, The Institute for Virus Research,2 Kyoto University, Kyoto, Japan

Received 19 November 1998/Accepted 12 March 1999

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 kappa B (NF-kappa B) in all cells examined. Deletion analysis of the core revealed that the region required for NF-kappa B 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-kappa B, Ikappa B-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-kappa B in particular cell lines.

* Corresponding author. Mailing address: Laboratory of Human Tumor Viruses, Department of Viral Oncology, The Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan. Phone: 81-75-751-4000. Fax: 81-75-751-3998. E-mail: mhijikat{at}virus.kyoto-u.ac.jp.

Journal of Virology, June 1999, p. 4713-4720, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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