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  • Original Paper
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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-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.

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References

  • Beasley RP, Hwang LY, Lin CC and Chien CS. . 1981 Lancet 2: 1129–1133.

  • Becker SA, Lee T, Butel JS and Slagle BL. . 1998 J. Virol. 72: 266–272.

  • Chisari FV, Klopchin K, Moriyama T, Pasquinelli C, Dunsford HA, Sell S, Pinkert CA, Brinster RL and Palmiter RD. . 1989 Cell 59: 1145–1156.

  • Chu CM, Yeh CT, Chiu CT, Sheen IS and Liaw YF. . 1996 J. Clin. Microbiol. 34: 1815–1818.

  • Dopheide TA and Azad AA. . 1996 J. Gen. Virol. 77: 173–176.

  • Dunsford HA, Sell S and Chisari FV. . 1990 Cancer Res. 50: 3400–3407.

  • Feitelson M. . 1992 Clin. Microbiol. Rev. 5: 275–301.

  • Feitelson MA, Duan LX, Guo J and Blumberg BS. . 1995 Gastroenterology 108: 1810–1819.

  • Feitelson MA, Zhu M, Duan LX and London WT. . 1993 Oncogene 8: 1109–1117.

  • Ganem D and Varmus HE. . 1987 Ann. Rev. Biochem. 56: 651–693.

  • Gottlob K, Fulco M, Levrero M and Graessmann A. . 1998a J. Biol. Chem. 273: 33347–33353.

  • Gottlob K, Pagano S, Levrero M and Graessmann A. . 1998b Cancer Res. 58: 8566–8570.

  • Greenblatt MS, Feitelson MA, Zhu M, Bennett WP, Welsh JA, Jones R, Borkowski A and Harris CC. . 1997 Cancer Res. 57: 426–432.

  • Hsia CC, Nakashima Y and Tabor E. . 1997 Biochem. Biophys. Res. Commun. 241: 726–729.

  • Kim CM, Koike K, Saito I, Miyamura T and Jay G. . 1991 Nature 351: 317–320.

  • Kim H, Lee H and Yun Y. . 1998 J. Biol. Chem. 273: 381–385.

  • Klein NP and Schneider RJ. . 1997 Mol. Cell. Biol. 17: 6427–6436.

  • Lee TH, Finegold MJ, Shen RF, DeMayo JL, Woo SLC and Butel JS. . 1990 J. Virol. 64: 5939–5947.

  • Lee YH and Yun Y. . 1998 J. Biol. Chem. 273: 25510–25515.

  • Liaw YF, Tai DI, Chu CM and Chen TJ. . 1988 Hepatology 8: 493–496.

  • Liaw YF. . 1994 Viral Hepatitis and Liver Disease: Viral Hepatitis in Taiwan: Status in the 1990s. Nishioka K, Suzuki H, Mishiro S and Oda T (eds). Springer-Verlag: Tokyo pp. 419–421.

  • Lucito R and Schneider RJ. . 1992 J. Virol. 66: 983–991.

  • Murakami S, Cheong JH and Kaneko S. . 1994 J. Biol. Chem. 269: 15118–15123.

  • Qadri I, Ferrari ME and Siddiqui A. . 1996 J. Biol. Chem. 271: 15443–15450.

  • Ohaki Y, Misugi K, Sasaki Y and Tsunoda A. . 1983 Cancer 51: 822–828.

  • Robinson WS. . 1994 Annu. Rev. Med. 45: 297–323.

  • Rossner MT. . 1992 J. Med. Virol. 36: 101–117.

  • Schuster R, Gerlich WH and Schaefer S. . 2000 Oncogene 19: 1173–1180.

  • Su F and Schneider RJ. . 1997 Proc. Natl. Acad. Sci. USA 94: 8744–8749.

  • Szmuness W. . 1979 Prog. Med. Virol. 24: 40–69.

  • Tai DI, Tsai SL, Chen YM, Chuang YL, Peng CY, Sheen IS, Yeh CT, Chang KS, Huang SN, Kuo GC and Liaw YF. . 2000 Hepatology 31: 656–664.

  • Tiollais P, Pourcel C and Dejean A. . 1985 Nature 317: 489–495.

  • Wang XW, Gibson MK, Vermeulen W, Yeh H, Forrester K, Sturzbecher HW, Hoeijmakers JH and Harris CC. . 1995 Cancer Res. 55: 6012–6016.

  • Wu JY, Zhou ZY, Judd A, Cartwright CA and Robinson WS. . 1990 Cell 63: 687–695.

  • Yeh CT, Shyu WC, Sheen IS, Chu CM and Liaw YF. . 1997 J. Virol. Methods 65: 219–226.

  • Yeh CT, Chiu HT, Chu CM and Liaw YF. . 1998 J. Med. Virol. 55: 42–50.

  • Yeh CT, Chien RN, Chu CM and Liaw YF. . 2000a Hepatology 31: 1318–1326.

  • Yeh CT, Sheen IS, Chen TC, Hsieh SY, Chu CM and Liaw YF. . 2000b J. Hepatol. 32: 829–836.

  • Yen TSB. . 1996 J. Biomed. Sci. 3: 20–30.

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Acknowledgements

This study is supported by grants from Chang Gung Medical Research Council (CMRP 605/996) and National Science Council, Taiwan (NSC 89-2315-B-182-003).

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Yeh, CT., Shen, CH., Tai, DI. et al. Identification and characterization of a prevalent hepatitis B virus X protein mutant in Taiwanese patients with hepatocellular carcinoma. Oncogene 19, 5213–5220 (2000). https://doi.org/10.1038/sj.onc.1203903

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