A comparative study of hepatitis B virus X protein mutants K130M, V131I and KV130/131MI to investigate their roles in fibrosis, cirrhosis and hepatocellular carcinoma.
Z I SiddiquiS R FarooquiS A AzamM AfrozS WajidS ParveenSyed Naqui KazimPublished in: Journal of viral hepatitis (2017)
Hepatitis B virus (HBV) genomic mutations A1762T, G1764A and AG1762/1764TA cause production of HBV X protein (HBx) mutants, namely K130M, V131I and KV130/131MI. These mutations are important biomarkers for the development of cirrhosis and hepatocellular carcinoma (HCC) in chronic HBV patients. This study comparatively analyses the impact of intracellular expression of HBx mutants on HCC cell line Huh7. It was found that expression of KV130/131MI induced: cell proliferation, altered expression of cell cycle regulatory genes in favour of cell proliferation, intracellular reactive oxygen species (ROS) production and mitochondrial depolarization. KV130/131MI may be directly involved in host cell proliferation and hepatocarcinogenesis via altering expression of cell cycle regulatory genes. KV130/131MI may also play pivotal roles in fibrosis and cirrhosis via inducing ROS production and mitochondrial depolarization. Furthermore, these might be the possible reasons for higher occurrence of AG1762/1764TA as compared to A1762T and G1764A in cirrhosis and HCC patients.
Keyphrases
- hepatitis b virus
- cell cycle
- cell proliferation
- reactive oxygen species
- poor prognosis
- liver failure
- end stage renal disease
- ejection fraction
- binding protein
- newly diagnosed
- oxidative stress
- prognostic factors
- peritoneal dialysis
- dna damage
- cell death
- pi k akt
- risk assessment
- genome wide
- magnetic resonance imaging
- dual energy
- copy number
- drug induced
- signaling pathway
- endothelial cells
- bioinformatics analysis
- genome wide analysis