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Abstract: Hepatitis B virus (HBV) may contribute to hepatocarcinogenesis by blocking p53 function. A p53 response element-like binding sequences, TGCCT⋯TGCCT, was found in HBV genome. To clarify whether HBV DNA can, like some other DNA viruses, bind to P53 protein and form a DNA–protein complex, we used a series of plasmids encoding full-length or mutant HBV or p53 fragments to determine the binding ability of HBV DNA after cotransfected into cells by electrophoretic mobility shift (and supershift) assay. We found that HBV DNA could bind to P53 protein and form DNA–protein complexes in human hepatoma cell lines. Cotransfection with p53 and HBV DNA increased the replication of HBV, CAT activity, tumor cell apoptosis, and cytoplasmic P53 accumulation in the hepatoma cells. In conclusions, our observations suggest that the interaction of HBV and p53 at the levels of protein–protein and DNA–protein, which resulted in inactivation of p53 transactivation. [Copyright &y& Elsevier]

Abstract: The role of the hepatitis B virus X protein (HBx) in hepatocarcinogenesis remains controversial. To investigate the biological impact of hepatitis B virus x gene (HBx) mutation on hepatoma cells, plasmids expressing the full-length HBx or HBx deletion mutants were constructed. The biological activities in these transfectants were analyzed by a series of assays. Results showed that HBx3′-20 and HBx3′-40 amino acid deletion mutants exhibited an increase in cellular proliferation, focus formation, tumorigenicity, and invasive growth and metastasis through promotion of the cell cycle from G0/G1 to the S phase, when compared with the full-length HBx. In contrast, HBx3′-30 amino acid deletion mutant repressed cell proliferation by blocking in G1 phase. The expression of P53, p21WAF1, p14ARF, and MDM2 proteins was regulated by expression of HBx mutants. In conclusions, HBx variants showed different effects and functions on cell proliferation and invasion by regulation of the cell cycle progression and its associated proteins expression. [Copyright &y& Elsevier]