Annuaire
HBx triggers either cellular senescence or cell proliferation depending on cellular phenotype.
J Viral Hepat, 23(2):130-8.
Replicative senescence is a hallmark of chronic liver diseases including chronichepatitis B virus (HBV) infection, whereas HBV-encoded oncoproteins HBx and preS2 have been found to overcome senescence. HBx possesses a C-terminal truncation mainly in hepatocellular carcinomas but also in noncancerous liver tissues. Here, by cell counting, BrdU incorporation, MTT proliferation assay, cell cycle analysis, SA-betagal staining and Western blotting in primary and malignant cells, we investigated the effect of HBx C-terminal mutants on cellular senescence. HBx C-terminal mutants were found to trigger cellular senescence in primary MRC5 cells, and malignant liver cells Huh7, and SK-Hep1. In contrast, these mutants promoted the proliferation of HepG2 malignant liver cells. The pro-senescent effect of HBx relied on an increased p16(INK4a) and p21(Waf1/Cip1)expression, and a decreased phosphorylation of Rb. Together, these results suggest that the two main variants of HBx present in HBV-infected liver possess opposite effects on cellular senescence that depend on the phenotype of infectedcells.
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