Identification and characterization of a prevalent hepatitis B virus X protein mutant in Taiwanese patients with hepatocellular carcinoma.
The aim of this study was to investigate whether there was a particular hepatitis B virus (HBV) X protein (HBx) mutant associated with Taiwanese patients with hepatocellular carcinoma (HCC). Initially, the entire coding region of HBx gene from the serum samples of 14 Taiwanese patients were sequenced. A novel mutant, HBx-A31, was preferentially found in patients with HCC. Sera from 67 patients with HCC and 100 patients with chronic hepatitis B were thus subjected for codon 31 analysis using a dual amplification created restriction site method. HBx-A31 was detected more frequently in patients with HCC (52% versus 12%; P<0.001) and in patients with liver cirrhosis (44% versus 6%; P<0.001). Site directed mutagenesis experiment revealed that HBx-A31 was less effective in transactivating HBV enhancer I-X promoter complex, less efficient in supporting HBV replication, and less potent in enhancing TNF-alpha induced increment of CPP32/caspase 3 activities in HepG2 cells. In conclusion, a prevalent HBx mutant was identified in Taiwanese patients with hepatocellular carcinoma. Development of this mutant might represent a strategy of the virus to escape immune surveillance and thus contribute to the process of multiple-step hepatocarcinogenesis.
Yeh
C T
CT
Liver Research Unit, Chang Gung Memorial Hospital, 199 Tung Hwa North Road, Taipei 105, Taiwan.
Shen
C H
CH
Tai
D I
DI
Chu
C M
CM
Liaw
Y F
YF
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000201:enzymology / Q000821:virology*; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D004742:Enhancer Elements, Genetic / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D015967:Gene Expression Regulation, Viral; D005787:Gene Frequency; D016679:Genome, Viral; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000150:complications / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000821:virology; D008113:Liver Neoplasms / Q000097:blood / Q000201:enzymology / Q000821:virology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D016415:Sequence Alignment; D013624:Taiwan; D015534:Trans-Activators / Q000235:genetics*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D054334:Viral Regulatory and Accessory Proteins; D014779:Virus Replication
D003062:Codon; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1