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

Abstract

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.

• Authors: Jingbo Pan, Ling-Xun Duan, Bill S Sun, Mark A Feitelson
• Journal: The Journal of general virology (J Gen Virol) Vol. 82 Issue Pt 1 Pg. 171-182 (Jan 2001) ISSN: 0022-1317 [Print] England
• PMID: 11125170 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA-Binding Proteins
• I-kappa B Proteins
• Immunoglobulin G
• NF-kappa B
• NFKBIA protein, human
• RNA, Messenger
• Trans-Activators
• Viral Regulatory and Accessory Proteins
• fas Receptor
• hepatitis B virus X protein
• NF-KappaB Inhibitor alpha

Topics

• Apoptosis
• Cells, Cultured
• DNA-Binding Proteins (analysis, genetics)
• Humans
• I-kappa B Proteins
• Immunoglobulin G (pharmacology)
• Liver (virology)
• NF-KappaB Inhibitor alpha
• NF-kappa B (metabolism)
• RNA, Messenger (analysis)
• Trans-Activators (genetics, physiology)
• Transcriptional Activation
• Transformation, Genetic
• Viral Regulatory and Accessory Proteins
• fas Receptor (physiology)