1887

Abstract

We have analysed abnormal virus RNAs produced from integrated woodchuck hepatitis virus (WHV) sequences in two woodchuck liver tumours. Analysis of cDNA clones revealed that these transcripts consisted of rearranged, virus-specific RNAs encoding the WHV surface antigens. In one tumour, transcription was driven by the major preS2/S promoter and terminated at a cryptic poly(A) signal in the 5′ end of the P gene, giving rise to a truncated version of the normal viral S message. In contrast, the integrated preS2/S promoter remained silent in the second tumour. The start sites of two abundant WHV transcripts encoding the large and middle surface proteins were localized about 100 bp upstream and 300 bp downstream of the preS1 translation initiation codon, corresponding to minor start sites of the normal surface protein mRNAs in chronically infected liver. Thus, the preS1 promoter, a weak promoter in episomal replicative forms of the virus, was activated in the integrated state in this tumour. Our results indicate that alternative usage of the preS1 or the preS2/S promoter in the integrated state may yield differential production of the three virus surface proteins in woodchuck liver tumours.

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1996-02-01
2022-05-19
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References

  1. Cattaneo R., Will H., Hernandez N., Schaller H. 1983; Signals regulating hepatitis B surface antigen transcription. Nature 305:336–340
    [Google Scholar]
  2. Cattaneo R., Will H., Schaller H. 1984; Hepatitis B virus transcription in the infected liver. EMBO Journal 3:2191–2196
    [Google Scholar]
  3. Chang H. K., Ting L. P. 1989; The surface gene promoter of the human hepatitis B virus displays a preference for differentiated hepatocytes. Virology 170:176–183
    [Google Scholar]
  4. Chisari F. V., Fillipi P., McLachlan A., Milich D., Riggs M., Lee S., Palmiter R., Pinkert C., Brinster R. 1986; Expression of hepatitis B large envelope polypeptide inhibits hepatitis B surface antigen secretion in transgenic mice. Journal of Virology 60:880–887
    [Google Scholar]
  5. Chisari F. V., Klopchin K., Moriyama T., Pasquinelli C., Dunsford H. A., Sell S., Pinkert C. A., Brinster R. L., Palmiter R. D. 1989; Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell 59:1145–1156
    [Google Scholar]
  6. Courtois G., Baumhueter S., Crabtree G. R. 1988; Purified hepatocyte nuclear factor 1 interacts with a family of hepatocyte specific promoters. Proceedings of the National Academy of Sciences, USA 85:7937–7941
    [Google Scholar]
  7. Enders G. H., Ganem D., Varmus H. 1985; Mapping the major transcripts of ground squirrel hepatitis virus: the presumptive template for reverse transcriptase is terminally redundant. Cell 42:297–308
    [Google Scholar]
  8. Etiemble J., Möröy T., Trepo C., Tiollais P., Buendia M. A. 1988; Transcription of woodchuck hepatitis virus in chronically infected liver and in hepatocellular carcinoma. In Viral Hepatitis and Liver Disease pp 484–487 Edited by Zuckermans A. J. New York: Alan R. Liss;
    [Google Scholar]
  9. Etiemble J., Degott C., Renard C. A., Fourel G., Shamoon B., Vitvitski-Trépo L., Hsu T. Y., Tiollais P., Babinet C., Buendia M. A. 1994; Liver-specific expression and high oncogenic efficiency of a c-myc transgene activated by woodchuck hepatitis virus insertion. Oncogene 9:727–737
    [Google Scholar]
  10. Fourel G., Trepo C., Bougueleret L., Henglein B., Ponzetto A., Tiollais P., Buendia M. A. 1990; Frequent activation of N-myc genes by hepadnavirus insertion in woodchuck liver tumours. Nature 347:294–298
    [Google Scholar]
  11. Fourel G., Transy C., Tennant B. C., Buendia M. A. 1992; Expression of the woodchuck N-myc2 retroposon in brain and in liver tumors is driven by a cryptic N-myc promoter. Molecular and Cellular Biology 12:5336–5344
    [Google Scholar]
  12. Fourel G., Couturier J., Wei Y., Apiou F., Tiollais P., Buendia M. A. 1994; Evidence for long-range oncogene activation by hepadnavirus insertion. EMBO Journal 13:2526–2534
    [Google Scholar]
  13. Freytag von Loringhoven A., Koch S., Hofschneider P. H., Koshy R. 1985; Co-transcribed 3′ host sequences augment expression of integrated hepatitis B virus DNA. EMBO Journal 4:249–255
    [Google Scholar]
  14. Galibert F., Chen T. N., Mandart E. 1982; Nucleotide sequence of a cloned woodchuck hepatitis virus genome: comparison with the hepatitis B virus sequence. Journal of Virology 41:51–65
    [Google Scholar]
  15. Hsu T. Y., Möröy T., Etiemble J., Louise A., Trepo C., Tiollais P., Buendia M. A. 1988; Activation of c-myc by woodchuck hepatitis virus insertion in hepatocellular carcinoma. Cell 55:627–635
    [Google Scholar]
  16. Imazeki F., Yaginuma K., Omata M., Okuda K., Kobayashi M., Koike K. 1987; RNA transcripts of hepatitis B virus in hepatocellular carcinoma. Hepatology 7:753–757
    [Google Scholar]
  17. Möröy T. 1987 Untersuchungen zur Rolle von Hepatitis B Virus bei der Entstehung von Hepatozellularen Karzinomen am Tiermodell Marmota Monax PhD thesis Ludwig; Maximilians University:
    [Google Scholar]
  18. Möröy T., Etiemble J., Trépo C., Tiollais P., Buendia M. A. 1985; Transcription of woodchuck hepatitis virus in the chronically infected liver. EMBO Journal 4:1507–1514
    [Google Scholar]
  19. Nakao K., Miyao Y., Ohe Y., Tamaoki T. 1989; Involvement of an AFP 1-binding site in cell-specific transcription of the pre-Sl region of the human hepatitis B virus surface antigen gene. Nucleic Acids Research 17:9833–9842
    [Google Scholar]
  20. Ou J. H., Rutter W. J. 1985; Hybrid hepatitis B virus-host transcripts in a human hepatoma cell. Proceedings of the National Academy of Sciences, USA 82:83–87
    [Google Scholar]
  21. Popper H., Roth L., Purcell R. H., Tennant B. C., Gerin J. L. 1987; Hepatocarcinogenicity of the woodchuck hepatitis virus. Proceedings of the National Academy of Sciences, USA 84:866–870
    [Google Scholar]
  22. Raney A. K., Milich D. R., Easton A. J., McLachlan A. 1990; Differentiation-specific transcriptional regulation of the hepatitis B virus large surface antigen gene in human hepatoma cell lines. Journal of Virology 64:2360–2368
    [Google Scholar]
  23. Sanger F., Nicklen S., Coulson A. R. 1977; DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, USA 74:5463–5467
    [Google Scholar]
  24. Terris B., Marchio A., Mattei M. G., Fagan E., Lock A., Tiollais P., Dejean A. 1992; Expression anormale de séquences du virus de l’hépatite B intégrées dans des carcinomes hépatocellulaires humains. Gastroenterologie Clinique et Biologique 16:511–517
    [Google Scholar]
  25. Tiollais P., Pourcel C., Dejean A. 1985; The hepatitis B virus. Nature 317:489–495
    [Google Scholar]
  26. Wei Y., Fourel G., Ponzetto A., Silvestro M., Tiollais P., Buendia M. A. 1992; Hepadnavirus integration: mechanisms of activation of the N-myc2 retro transposon in woodchuck liver tumors. Journal of Virology 66:5265–5276
    [Google Scholar]
  27. Wei Y., Etiemble J., Fourel G., Vitvitski-Trépo L., Buendia M. A. 1995; Hepadnavirus integration generates virus-cell cotranscripts carrying 3′ truncated X genes in human and woodchuck liver tumors. Journal of Medical Virology 45:82–90
    [Google Scholar]
  28. Yaginuma K., Kobayashi M., Yoshida E., Koikb K. 1985; Hepatitis B virus integration in hepatocellular carcinoma DNA: duplication of cellular flanking sequences at the integration site. Proceedings of the National Academy of Sciences, USA 82:4458–4462
    [Google Scholar]
  29. Zhou D. X., Yen T. S. B. 1991; The ubiquitous transcription factor Oct-1 and the liver-specific factor HNF-1 are both required to activate transcription of a hepatitis B virus promoter. Molecular and Cellular Biology 11:1353–1359
    [Google Scholar]
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