1887

Abstract

The hepatitis B virus (HBV) e antigen (HBeAg) is a 15 kDa soluble antigen derived from a precursor protein (precore protein) by two processing events, cleavage of the N-terminal signal peptide and cleavage of the C-terminal 34 amino acids. So far, the role of the C-terminal sequences in secretion has not been analysed in full. In this study deletion of the last 60 amino acids was found to abrogate HBeAg secretion whereas deletions of the last 10, 25 or 39 amino acids decreased its secretion rate. These data demonstrate that C-terminal precore protein sequences are crucial for HBe secretion and determine its secretion rate.

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1995-04-01
2022-01-19
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References

  1. Bruss V., Gerlich W. H. 1988; Formation of transmembraneous hepatitis B e-antigen by cotranslational in vitro processing of the viral precore protein. Virology 163:268–275
    [Google Scholar]
  2. Carlier D., Jean-Jean O., Rossignol J. M. 1994; Characterization and biosynthesis of the woodchuck hepatitis virus e antigen. Journal of General Virology 75:171–175
    [Google Scholar]
  3. Garcia P. D., Ou J.-H., Rutter W. J., Walter P. 1988; Targeting of the hepatitis B vims precore protein to the endoplasmic reticulum membrane: after signal peptide cleavage translocation can be aborted and the product released into the cytoplasm. Journal of Cell Biology 106:1093–1104
    [Google Scholar]
  4. Graham F. L., Van der Eb A. J. 1973; A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 52:456–467
    [Google Scholar]
  5. Günther S., Meisel H., Reip A., Miska S., Krüger D., 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]
  6. Harrisson T., Graham F. L., William J. 1977; Host-range mutant of adenovirus type 5 defective for growth in HeLa cells. Virology 77:319–329
    [Google Scholar]
  7. Jean-Jean O., Levrero M., Will H., Rossignol J.-M., Perri-caudet M. 1987; High level expression of hepatitis B virus C-ORF in human cells. In Hepadna Viruses pp 223–235 Edited by Robinson W., Koike K., Will H. New York: A. R. Liss;
    [Google Scholar]
  8. Jean-Jean O., Levrero M., Will H., Perricaudet M., Rossignol J.-M. 1989a; Expression mechanism of the hepatitis B virus (HBV) C gene and biosynthesis of the HBe antigen. Virology 170:99–106
    [Google Scholar]
  9. Jean-Jean O., Salhi S., Carlier D., Elie C., de Recondo A.-M., Rossignol J.-M. 1989b; Biosynthesis of hepatitis B virus e antigen: directed mutagenesis of the putative aspartyl protease site. Journal of Virology 63:5497–5500
    [Google Scholar]
  10. Junker M., Galle P., Schaller H. 1987; Expression and replication of the hepatitis B vims genome under foreign promoter control. Nucleic Acids Research 15:10117–10132
    [Google Scholar]
  11. Klionsky D. J., Banta L. M., Emr S. D. 1988; Intracellular sorting and processing of a yeast vacuolar hydrolase: proteinase A propeptide contains vacuolar targeting information. Molecular and Cellular Biology 8:2105–2116
    [Google Scholar]
  12. Laemmli U. K. 1970; Cleavage of structural protein during the assembly of the head of bacteriophage T4. Nature 227:680–685
    [Google Scholar]
  13. Milich D. R., Jones J. E., Hugues J. L., Price J., Raney A. K., McLachlan A. 1990; Is a function of the secreted hepatitis B e antigen to induce immunologic tolerance in utero . Proceedings of the National Academy of Sciences, USA 87:6599–6603
    [Google Scholar]
  14. Miska S., Günther S., Vassilev M., Meisel H., Pape G., Will H. 1993; Heterogeneity of hepatitis B virus C gene sequences: implications for amplification and sequencing. Journal of Hepatology 18:53–61
    [Google Scholar]
  15. Nassal M., Rieger A. 1993; An intramolecular disulfide bridge between cys-7 and cys-61 determines the structure of the secretory core gene product (e antigen) of hepatitis B virus. Journal of Virology 67:4307–4315
    [Google Scholar]
  16. Nassal M., Galle P. R., Schaller H. 1989; Proteaselike sequence in hepatitis B vims core antigen is not required for e antigen generation and may not be part of an aspartic acid-type protease. Journal of Virology 63:2598–2604
    [Google Scholar]
  17. Sällberg M., Pushko P., Berzinsh I., Bichko V., Sillekens P., Noah M., Pumpens P., Grens E., Wahren B., Magnius L. O. 1993; Immunochemical structure of the carboxy-terminal part of hepatitis B e antigen: identification of internal and surface-exposed sequences. Journal of General Virology 74:1335–1340
    [Google Scholar]
  18. Schlicht H. J. 1991; Biosynthesis of the secretory core protein of duck hepatitis B virus: intracellular transport, proteolytic processing, and membrane expression of the precore protein. Journal of Virology 65:3489–3495
    [Google Scholar]
  19. Schlicht H. J., Wasenauer G. 1991; The quaternary stmcture, antigenicity, and aggregational behavior of the secretory core protein of human hepatitis B virus are determined by its signal sequence. Journal of Virology 65:6817–6825
    [Google Scholar]
  20. Schlicht H. J., Salfeld J., Schaller H. 1987; The duck hepatitis B virus pre-C region encodes a signal sequence which is essential for synthesis and secretion of processed core proteins but not for virus formation. Journal of Virology 61:3701–3709
    [Google Scholar]
  21. Sha X., Liang L., Gentry L. E. 1991; Identification and analysis of discrete functional domains in the Pro region of Pre-Protransforming growth factor Beta 1. Journal of Cell Biology 114:827–839
    [Google Scholar]
  22. Takahashi K., Machida A., Funatsu G., Nomura M., Usuda S., Aoyagi S., Tachibana K., Miyamoto H., Imai M., Nakamura T., Miyakawa Y., Mayumi M. 1983; Immunochemical stmcture of hepatitis B e antigen in the serum. Journal of Immunology 130:2903–2907
    [Google Scholar]
  23. Takahashi K., Kishimoto S., Oshiro K., Yoshizawa H., Machida A., Ohnuma H., Tsuda F., Munekata E., Miyakawa Y., Mayumi M. 1992; Molecular heterogeneity of e-antigen polypeptides in sera from carriers of hepatitis B virus. Journal of Immunology 147:3156–3160
    [Google Scholar]
  24. Tong S., Diot C., Gripon P., Li J., Vitvitski L., Trepo C., Guguen-Guillouzo C. 1991; In vitro replication competence of a cloned hepatitis B virus variant with a nonsense mutation in the distal pre-C region. Virology 181:733–737
    [Google Scholar]
  25. Wang J., lee A. S., Ou J.-H. 1991; Proteolytic conversion of hepatitis B virus e antigen precursor to end product occurs in a postendoplasmic reticulum compartment. Journal of Virology 65:5080–5083
    [Google Scholar]
  26. Wasenauer G., Köck J., Schlicht H.-J. 1992; A cysteine and a hydrophobic sequence in the noncleaved portion of the pre-C leader peptide determine the biophysical properties of the secretory core protein (HBe protein) of human hepatitis B vims. Journal of Virology 66:5338–5346
    [Google Scholar]
  27. Wasenauer G., Köck J., Schlicht H.-J. 1993; Relevance of cysteine residues for biosynthesis and antigenicity of human hepatitis B vims e protein. Journal of Virology 67:1315–1321
    [Google Scholar]
  28. Weimer T., Salfeld J., Will H. 1987; Expression of the hepatitis B virus core gene in vitro and in vivo . Journal of Virology 61:3109–3113
    [Google Scholar]
  29. Zoller M. J., Smith H. 1984; Oligonucleotide-directed mutagenesis: a simple method using two oligonucleotide primers and a single-stranded DNA template. DNA 3:479–488
    [Google Scholar]
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