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A comparative study of hepatitis B virus X protein mutants K130M, V131I and KV 130/131 MI to investigate their roles in fibrosis, cirrhosis and hepatocellular carcinoma
Author(s) -
Siddiqui Z. I.,
Farooqui S. R.,
Azam S. A.,
Afroz M.,
Wajid S.,
Parveen S.,
Kazim S. N.
Publication year - 2017
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.12747
Subject(s) - cirrhosis , hepatocellular carcinoma , hepatitis b virus , intracellular , cancer research , cell growth , cell , cell cycle , biology , mutant , cell culture , virus , virology , medicine , gene , microbiology and biotechnology , genetics
Summary Hepatitis B virus ( HBV ) genomic mutations A1762T, G1764A and AG 1762/1764 TA cause production of HBV X protein ( HB x) mutants, namely K130M, V131I and KV 130/131 MI . 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 HB x mutants on HCC cell line Huh7. It was found that expression of KV 130/131 MI induced: cell proliferation, altered expression of cell cycle regulatory genes in favour of cell proliferation, intracellular reactive oxygen species ( ROS ) production and mitochondrial depolarization. KV 130/131 MI may be directly involved in host cell proliferation and hepatocarcinogenesis via altering expression of cell cycle regulatory genes. KV 130/131 MI 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 AG 1762/1764 TA as compared to A1762T and G1764A in cirrhosis and HCC patients.