1887

Abstract

Hepatitis B virus (HBV) isolates with A-1762 to T and G-1764 to A mutations in the core promoter have been associated with active hepatitis, severe liver disease following liver transplantation, hepatocellular carcinoma and acute fulminant courses-in the latter case combined with a C- 1653 to T mutation. In this study, a mutant core promoter region containing the T-1653, T-1762 and A-1764 mutations was placed into the context of a wild-type HBV genome and analysed by transfection. The mutations reduced the level of pre-C mRNA (by 55%) and e-antigen secretion. In contrast, no significant effects on the levels of pregenome/C and pre-S/S mRNAs, intracellular core, polymerase, and pre-S1/S2 proteins and secreted S-antigen were observed. The amount of progeny virus DNA in the cells and in the culture medium was increased marginally, if at all.

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1998-02-01
2022-11-27
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References

  1. Buckwold V. E., Xu Z. C., Chen M., Yen T. S. B., Ou J. H. 1996; Effects of a naturally occurring mutation in the hepatitis B virus basal core promoter on precore gene expression and viral replication. Journal of Virology 70:5845–5851
    [Google Scholar]
  2. Chen I. H., Huang C. J., Ting L. P. 1995; Overlapping initiator and TATA box functions in the basal core promoter of hepatitis B virus. Journal of Virology 69:3647–3657
    [Google Scholar]
  3. Chomczynski P., Sacchi N. 1987; Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Analytical Biochemistry 162:156–159
    [Google Scholar]
  4. Cullen B. R., Malim M. H. 1992; Secreted placental alkaline phosphatase as a eukaryotic reporter gene. Methods in Enzymology 216:326–368
    [Google Scholar]
  5. Galibert F., Mandart E., Fitoussi F., Tiollais P., Charnay P. 1979; Nucleotide sequence of the hepatitis B genome (subtype ayw) cloned in E. coli . Nature 281:646–650
    [Google Scholar]
  6. Guidotti L. G., Matzke B., Pasquinelli C., Shoenberger J. M., Rogler C. E., Chisari F. V. 1996; The hepatitis B virus (HBV) precore protein inhibits HBV replication in transgenic mice. Journal of Virology 70:7056–7061
    [Google Scholar]
  7. Günther S., Meisel H., Reip A., Miska S., Krüger D. H., Will H. 1992; Frequent and rapid emergence of mutated pre-C sequences in HBV from e-antigen positive carriers who seroconvert to anti-HBe during interferon treatment. Virology 187:271–279
    [Google Scholar]
  8. Günther S., Li B. C., Miska S., Krüger D. H., Meisel H., Will H. 1995; A novel method for efficient amplification of whole hepatitis B virus genomes permits rapid functional analysis and reveals deletion mutants in immunosuppressed patients. Journal of Virology 69:5437–5444
    [Google Scholar]
  9. Günther S., Piwon N., Iwanska A., Schilling R., Meisel H., Will H. 1996; Type, prevalence, and significance of core promoter/enhancer II mutations in hepatitis B viruses from immunosuppressed patients with severe liver disease. Journal of Virology 70:8318–8331
    [Google Scholar]
  10. Hasegawa K., Huang J., Rogers S. A., Blum H. E., Liang T. J. 1994; Enhanced replication of a hepatitis B virus mutant associated with an epidemic of fulminant hepatitis. Journal of Virology 68:1651–1659
    [Google Scholar]
  11. Horikita M., Itoh S., Yamamoto K., Shibayama T., Tsuda F., Okamoto H. 1994; Differences in the entire nucleotide sequence between hepatitis B virus genomes from carriers positive for antibody to hepatitis B e antigen with and without active disease. Journal of Medical Virology 44:96–103
    [Google Scholar]
  12. Hsia C. C., Yuwen H., Tabor E. 1996; Hot-spot mutations in hepatitis B virus X gene in hepatocellular carcinoma. Lancet 348:625–626
    [Google Scholar]
  13. Kaneko M., Uchida T., Moriyama M., Arakawa Y., Shikata T., Gotoh K., Mima S. 1995; Probable implication of mutations of the X open reading frame in the onset of fulminant hepatitis B. Journal of Medical Virology 47:204–208
    [Google Scholar]
  14. Kidd A. H., Kidd-Ljunggren K. 1996; A revised secondary structure model for the 3ʹ-end of hepatitis B virus pregenomic RNA. Nucleic Acids Research 24:3295–3301
    [Google Scholar]
  15. Kidd-Ljunggren K., Öberg M., Kidd A. H. 1995; The hepatitis B virus X gene: analysis of functional domain variation and gene phylogeny using multiple sequences. Journal of General Virology 76:2119–2130
    [Google Scholar]
  16. Kidd-Ljunggren K., Öberg M., Kidd A. H. 1997; Hepatitis B virus X gene 1751 to 1764 mutations: implications for HBeAg status and disease. Journal of General Virology 78:1469–1478
    [Google Scholar]
  17. Kurosaki M., Enomoto N., Asahina Y., Sakuma I., Ikeda T., Tozuka S., Izumi N., Marumo F., Sato C. 1996; Mutations in the core promoter region of hepatitis B virus in patients with chronic hepatitis B. Journal of Medical Virology 49:115–123
    [Google Scholar]
  18. Lamberts C., Nassal M., Velhagen I., Zentgraf H., Schröder C. H. 1993; Precore-mediated inhibition of hepatitis B virus progeny DNA synthesis. Journal of Virology 67:3756–3762
    [Google Scholar]
  19. Laskus T., Rakela J., Nowicki M. J., Persing D. H. 1995; Hepatitis B virus core promoter sequence analysis in fulminant and chronic hepatitis B. Gastroenterology 109:1618–1623
    [Google Scholar]
  20. López-Cabrera M., Letovsky J., Hu K.-Q., Siddiqui A. 1990; Multiple liver-specific factors bind to the hepatitis B virus core/ pregenomic promoter: trans-activation and repression by CCAAT/ enhancer binding protein. Proceedings of the National Academy of Sciences, USA 87:5069–5073
    [Google Scholar]
  21. McMillan J. S., Bowden D. S., Angus P. W., McCaughan G. W., Locarnini S. A. 1996; Mutations in the hepatitis B virus precore/core gene and core promoter in patients with severe recurrent disease following liver transplantation. Hepatology 24:1371–1378
    [Google Scholar]
  22. Miska S. 1996 Vorkommen, Selektion und Bedeutung von Hepatitis B virus C-Gen Varianten PhD thesis University of Hamburg; Germany:
    [Google Scholar]
  23. Moriyama K., Okamoto H., Tsuda F., Mayumi M. 1996; Reduced precore transcription and enhanced core-pregenome transcription of hepatitis B virus DNA after replacement of the precore-core promoter with sequences associated with e antigen-seronegative persistent infections. Virology 226:269–280
    [Google Scholar]
  24. Nishizono A., Hiraga M., Kohno K., Sonoda Y. T., Terao H., Fujioka T., Nasu M., Mifune K. 1995; Mutations in the core promoter/ enhancer II regions of naturally occurring hepatitis B virus variants and analysis of the effects on transcription activities. Intervirology 38:290–294
    [Google Scholar]
  25. Ogata N., Miller R. H., Ishak K. G., Purcell R. H. 1993; The complete nucleotide sequence of a pre-core mutant of hepatitis B virus implicated in fulminant hepatitis and its biological characterization in chimpanzees. Virology 194:263–276
    [Google Scholar]
  26. Okamoto H., Yotsumoto S., Akahane Y., Yamanaka T., Miyazaki Y., Sugai Y., Tsuda F., Tanaka T., Miyakawa Y., Mayumi M. 1990; Hepatitis B viruses with precore region defects prevail in persistently infected hosts along with seroconversion to the antibody against e antigen. Journal of Virology 64:1298–1303
    [Google Scholar]
  27. Okamoto H., Tsuda F., Akahane Y., Sugai Y., Yoshiba M., Moriyama K., Tanaka T., Miyakawa Y., Mayumi M. 1994; Hepatitis B virus with mutations in the core promoter for an e antigen-negative phenotype in carriers with antibody to e antigen. Journal of Virology 68:8102–8110
    [Google Scholar]
  28. Raney A. R., Johnson J. L., Palmer C. N. A., McLachlan A. 1997; Members of the nuclear receptor superfamily regulate transcription from the hepatitis B virus nucleocapsid promoter. Journal of Virology 71:1058–1071
    [Google Scholar]
  29. Sato S., Suzuki K., Akahane Y., Akamatsu K., Akiyama K., Yunomura K., Tsuda F., Tanaka T., Okamoto H., Miyakawa Y., Mayumi M. 1995; Hepatitis B virus strains with mutations in the core promoter in patients with fulminant hepatitis. Annals of Internal Medicine 122:241–248
    [Google Scholar]
  30. Scaglioni P. P., Melegari M., Wands J. R. 1997a; Biologic properties of hepatitis B viral genomes with mutations in the precore promoter and precore open reading frame. Virology 233:374–381
    [Google Scholar]
  31. Scaglioni P. P., Melegari M., Wands J. R. 1997b; Posttranscriptional regulation of hepatitis B virus replication by the precore protein. Journal of Virology 71:345–353
    [Google Scholar]
  32. Takahashi K., Aoyama K., Ohno N., Iwata K., Akahane Y., Baba K., Yoshizawa H., Mishiro S. 1995; The precore/core promoter mutant (T1762 A1764) of hepatitis B virus: clinical significance and an easy method for detection. Journal of General Virology 76:3159–3164
    [Google Scholar]
  33. Tong S. P., Li J. S., Vitvitski L., Trepo C. 1992; Replication capacities of natural and artificial precore stop codon mutants of hepatitis B virus: relevance of pregenome encapsidation signal. Virology 191:237–245
    [Google Scholar]
  34. Yuan T. T. T., Faruqi A., Shih J. W., Shih C. 1995; The mechanism of natural occurrence of two closely linked HBV precore predominant mutations. Virology 211:144–156
    [Google Scholar]
  35. Yuh C. H., Ting L. P. 1991; e functional box-alpha and box-beta of the second enhancer of hepatitis B virus. Molecular and Cellular Biology 11:5044–5052
    [Google Scholar]
  36. Yuh C. H., Chang Y. L., Ting L. P. 1992; Transcriptional regulation of precore and pregenomic RNAs of hepatitis B virus. Journal of Virology 66:4073–4084
    [Google Scholar]
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