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 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.
Pan
Jingbo
J
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Room 222 Alumni Hall, 1020 Locust Street, Philadelphia, PA 19107-6799, USA1.
Duan
Ling-Xun
LX
GenWay Biotech, Inc., Suite E-2 Welsh Commons, 1364 Welsh Road, North Wales, PA 19454, USA3.
Sun
Bill S
BS
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Room 222 Alumni Hall, 1020 Locust Street, Philadelphia, PA 19107-6799, USA1.
Feitelson
Mark A
MA
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA2.|Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Room 222 Alumni Hall, 1020 Locust Street, Philadelphia, PA 19107-6799, USA1.
D017209:Apoptosis; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D006801:Humans; D020672:I-kappa B Proteins; D007074:Immunoglobulin G / Q000494:pharmacology; D008099:Liver / Q000821:virology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D014170:Transformation, Genetic; D054334:Viral Regulatory and Accessory Proteins; D019014:fas Receptor / Q000502:physiology*
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007074:Immunoglobulin G; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; D019014:fas Receptor; C057628:hepatitis B virus X protein; D000072000:NF-KappaB Inhibitor alpha