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

Chau Ting Yeh*, Chien Hong Shen, Dar In Tai, Chia-Ming Chu, Yun Fan Liaw

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

66 Scopus citations

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-α 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.

Original languageEnglish
Pages (from-to)5213-5220
Number of pages8
JournalOncogene
Volume19
Issue number46
DOIs
StatePublished - 02 11 2000
Externally publishedYes

Keywords

  • Hepatitis B virus
  • Hepatocellular carcinoma
  • Mutant
  • X protein

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