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HB x triggers either cellular senescence or cell proliferation depending on cellular phenotype
Author(s) -
Idrissi M. E.,
Hachem H.,
Koering C.,
Merle P.,
Thénoz M.,
Mortreux F.,
Wattel E.
Publication year - 2016
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12450
Subject(s) - hbx , senescence , cell growth , phenotype , biology , telomere , cancer research , blot , cell cycle , mutant , cell , microbiology and biotechnology , cell culture , transfection , genetics , gene
Summary Replicative senescence is a hallmark of chronic liver diseases including chronic hepatitis B virus ( HBV ) infection, whereas HBV ‐encoded oncoproteins HB x and pre S 2 have been found to overcome senescence. HB x possesses a C ‐terminal truncation mainly in hepatocellular carcinomas but also in noncancerous liver tissues. Here, by cell counting, B rd U incorporation, MTT proliferation assay, cell cycle analysis, SA ‐ β gal staining and W estern blotting in primary and malignant cells, we investigated the effect of HB x C ‐terminal mutants on cellular senescence. HB x C ‐terminal mutants were found to trigger cellular senescence in primary MRC 5 cells, and malignant liver cells H uh7, and SK ‐ H ep1. In contrast, these mutants promoted the proliferation of H ep G 2 malignant liver cells. The pro‐senescent effect of HB x relied on an increased p16 INK4a and p21 Waf1/Cip1 expression, and a decreased phosphorylation of R b. Together, these results suggest that the two main variants of HB x present in HBV ‐infected liver possess opposite effects on cellular senescence that depend on the phenotype of infected cells.