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The hepatitis B virus X protein up‐regulates tumor necrosis factor α gene expression in hepatocytes
Author(s) -
LaraPezzi Enrique,
Majano Pedro L.,
GómezGonzalo Marta,
GarcíaMonzón Carmelo,
MorenoOtero Ricardo,
Levrero Massimo,
LópezCabrera Manuel
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510280416
Subject(s) - hbx , tumor necrosis factor alpha , transfection , hepatitis b virus , microbiology and biotechnology , biology , proinflammatory cytokine , hepatocyte , cell culture , interferon , gene expression , luciferase , cancer research , virology , virus , gene , immunology , inflammation , in vitro , biochemistry , genetics
Human hepatocytes infected by hepatitis B virus (HBV) produce the proinflammatory cytokine, tumor necrosis factor α (TNF‐α). In this study, we explored the mechanism of induction of TNF‐α synthesis by HBV. We found that the stable HBV‐transfected hepatoma cell line, 2.2.15, expressed high‐molecular‐weight (HMW) TNF‐α mRNAs, which were absent in the parent HepG2 cells. Treatment of 2.2.15 cells with interferon alfa (IFN‐α) and/or interleukin‐1β (IL‐1β) reduced both viral gene transcription and TNF‐α mRNA expression. Transient or stable transfection of hepatocyte‐derived cell lines with HBV X protein (HBx) expression vectors induced the production of biologically active TNF‐α. In these cells, the HBx‐induced TNF‐α was detected both as cell‐associated and soluble forms. Luciferase gene‐expression assays showed that the TNF‐α gene promoter contained target sequences for HBx trans‐activation within the proximal region of the promoter. These results indicate that the hepatocyte TNF‐α synthesis induced by HBV is transcriptionally up‐regulated by HBx. Thus, HBx may have a role in the induction of the intrahepatic inflammatory processes that take place during acute and chronic hepatitis B.