Hepatitis B virus X protein protects against anti-Fas-mediated apoptosis in human liver cells by inducing NF-kappa B

The hepatitis B virus-encoded X antigen (HBxAg) may contribute to the development of liver cancer, in part, by stimulating the growth and survival of infected cells in the face of ongoing immune responses. Given that the Fas ligand/receptor system contributes to the pathogenesis of chronic hepatitis...

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Bibliographic Details
Published in:Journal of general virology 2001-01, Vol.82 (Pt 1), p.171-182
Main Authors: Pan, Jingbo, Duan, Ling-Xun, Sun, Bill S, Feitelson, Mark A
Format: Article
Language:English
Subjects:
Apoptosis
AX protein
Cells, Cultured
DNA-Binding Proteins - analysis
DNA-Binding Proteins - genetics
Fas antigen
fas Receptor - physiology
Hepatitis B virus
Humans
I-kappa B Proteins
I^KB^a protein
Immunoglobulin G - pharmacology
Liver - virology
NF-^KB protein
NF-kappa B - metabolism
NF-KappaB Inhibitor alpha
RNA, Messenger - analysis
Trans-Activators - genetics
Trans-Activators - physiology
Transcriptional Activation
Transformation, Genetic
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Summary:The hepatitis B virus-encoded X antigen (HBxAg) may contribute to the development of liver cancer, in part, by stimulating the growth and survival of infected cells in the face of ongoing immune responses. Given that the Fas ligand/receptor system contributes to the pathogenesis of chronic hepatitis B, experiments were designed to test the hypothesis that HBxAg mediates resistance of liver cells to anti-Fas killing. Accordingly, when HBxAg was introduced into HepG2 cells, it rendered these cells partially resistant to killing by anti-Fas. In HepG2 cells replicating virus, protection against anti-Fas killing was also observed, but to a lesser extent. Survival correlated with the activation of nuclear factor kappa B (NF-kappa B) by HBxAg. Sensitivity to anti-Fas was observed in control cells, and was re-established in HepG2X cells stably transfected with the dominant negative inhibitor of NF-kappa B, I kappa B alpha. HBxAg activation of NF-kappa B was also associated with decreased levels of endogenous I kappa B alpha mRNA. Hence, HBxAg stimulation of NF-kappa B promotes the survival of liver cells against Fas killing. This may contribute to the persistence of infected hepatocytes during chronic infection.
ISSN:0022-1317
1465-2099
DOI:10.1099/0022-1317-82-1-171