Identification and characterization of a prevalent hepatitis B virus X protein mutant in Taiwanese patients with hepatocellular carcinoma.

Abstract

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.

• Authors: C T Yeh, C H Shen, D I Tai, C M Chu, Y F Liaw
• Journal: Oncogene (Oncogene) Vol. 19 Issue 46 Pg. 5213-20 (Nov 02 2000) ISSN: 0950-9232 [Print] England
• PMID: 11077437 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Codon
• Trans-Activators
• Tumor Necrosis Factor-alpha
• Viral Regulatory and Accessory Proteins
• hepatitis B virus X protein
• CASP3 protein, human
• Caspase 3
• Caspases
• Caspase 1

Topics

• Amino Acid Sequence
• Amino Acid Substitution (genetics)
• Base Sequence
• Carcinoma, Hepatocellular (blood, enzymology, virology)
• Caspase 1 (metabolism)
• Caspase 3
• Caspases (metabolism)
• Codon (genetics)
• DNA Mutational Analysis
• Enhancer Elements, Genetic (genetics)
• Enzyme Activation (drug effects)
• Gene Expression Regulation, Viral
• Gene Frequency
• Genome, Viral
• Hepatitis B virus (genetics, physiology)
• Hepatitis B, Chronic (complications, virology)
• Humans
• Liver Cirrhosis (complications, virology)
• Liver Neoplasms (blood, enzymology, virology)
• Molecular Sequence Data
• Mutation (genetics)
• Promoter Regions, Genetic (genetics)
• Sequence Alignment
• Taiwan
• Trans-Activators (genetics)
• Transcriptional Activation
• Tumor Cells, Cultured
• Tumor Necrosis Factor-alpha (pharmacology)
• Viral Regulatory and Accessory Proteins
• Virus Replication