HBx triggers either cellular senescence or cell proliferation depending on cellular phenotype.

Area of Science:

• Hepatology
• Molecular Biology
• Cellular Biology

Background:

• Replicative senescence is a key feature of chronic liver diseases, including chronic hepatitis B virus (HBV) infection.
• HBV-encoded oncoproteins, such as HBx, are known to influence cellular senescence pathways.
• HBx C-terminal truncation is observed in both cancerous and noncancerous liver tissues from HBV-infected individuals.

Purpose of the Study:

• To investigate the impact of HBx C-terminal mutants on cellular senescence.
• To determine how HBx variants affect proliferation and senescence in different liver cell types.

Main Methods:

• Utilized cell counting, BrdU incorporation, MTT proliferation assays, cell cycle analysis, SA-βgal staining, and Western blotting.
• Examined primary human lung fibroblast (MRC5) cells and various malignant liver cell lines (Huh7, SK-Hep1, HepG2).
• Assessed the expression of senescence markers like p16(INK4a), p21(Waf1/Cip1), and retinoblastoma protein (Rb) phosphorylation.

Main Results:

• HBx C-terminal mutants induced cellular senescence in primary MRC5 cells and in Huh7 and SK-Hep1 malignant liver cells.
• Conversely, these HBx mutants promoted proliferation in HepG2 malignant liver cells.
• The pro-senescence effects were linked to increased p16(INK4a) and p21(Waf1/Cip1) expression and reduced Rb phosphorylation.

Conclusions:

• The two main HBx variants found in HBV-infected livers exhibit opposing effects on cellular senescence.
• The outcome of HBx on cellular senescence is dependent on the specific phenotype of the infected liver cells.
• These findings highlight the complex role of HBx in the pathogenesis of chronic liver diseases.