1887

Abstract

To study the mechanism of L protein-mediated, intracellular (pre-Golgi) retention of hepatitis B virus (HBV) surface proteins, a collection of HBV open reading frame variants bearing wild-type or modified extensions was expressed in human cells. When the secretion phenotype of the corresponding proteins was analysed, all surface proteins with rearranged preS domains were found to be at least partially retained. This held true, in particular, for two variant proteins lacking preSl amino acids 1 to 19 (ayw), the preSl myristylated N terminus and a putative retention domain, and for another variant lacking the entire preSl domain plus the N-terminal portion (amino acids 1 to 12) of the preS2 domain. All the retained variants underwent intracellular dimerization/oligomerization via disulphide bonds to a degree comparable to that observed in well exported natural proteins. Our results show that retention can take place in the absence of L N-terminal sequences and does not imply inhibition of covalent oligomerization.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-75-2-449
1994-02-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/75/2/JV0750020449.html?itemId=/content/journal/jgv/10.1099/0022-1317-75-2-449&mimeType=html&fmt=ahah

References

  1. Blum H. E., Gerok W., Vyas G. N. 1989; The molecular biology of hepatitis B virus. Trends in Genetics 5:154–158
    [Google Scholar]
  2. Bruss V., Ganem D. 1991a; Mutational analysis of hepatitis B surface antigen particle assembly and secretion. Journal of Virology 65:3813–3820
    [Google Scholar]
  3. Bruss V., Ganem D. 1991b; The role of envelope proteins in hepatitis B virus assembly. Proceedings of the National Academy of Sciences, U.S.A 88:1059–1063
    [Google Scholar]
  4. Cheng K., Moss B. 1987; Selective synthesis and secretion of particles composed of the hepatitis B virus middle surface protein directed by a recombinant vaccinia virus: induction of antibodies to pre-S and S epitopes. Journal of Virology 61:1286–1290
    [Google Scholar]
  5. Cheng K., Smith G. L., Moss B. 1986; Hepatitis B virus large surface protein is not secreted but is immunogenic when selectively expressed by recombinant vaccinia virus. Journal of Virology 60:337–344
    [Google Scholar]
  6. Chisari F. V., Filippi P., McLachlan A., Milich D. R., Riggs M., Lee S., Palmiter R. D., Pinkert C. A., Brinster R. L. 1986; Expression of hepatitis B virus large envelope polypeptide inhibits hepatitis B surface antigen secretion in transgenic mice. Journal of Virology 60:880–887
    [Google Scholar]
  7. Chisari F., Klopchin K., Moriyama T., Pasquinelli C., Duns-Ford H., Sell S., Pinkert C., Brinster R., Palmiter R. 1989; Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell 59:1145–1156
    [Google Scholar]
  8. Delos S., Villar M. T., Hu P., Peterson D. 1991; Cloning, expression, isolation and characterization of the pre-S domains of hepatitis B surface antigen, devoid of the S protein. Biochemical Journal 276:411–116
    [Google Scholar]
  9. Eble B., Lingappa V., Ganem D. 1986; Hepatitis B surface antigen: an unusual secreted protein initially synthesized as a transmembrane polypeptide. Molecular and Cellular Biology 6:1454–1463
    [Google Scholar]
  10. Eble B., MacRae D., Lingappa V., Ganem D. 1987; Multiple topogenic sequences determine the transmembrane orientation of hepatitis B surface antigen. Molecular and Cellular Biology 7:3591–3601
    [Google Scholar]
  11. Eble B., Lingappa V., Ganem D. 1990; The N-terminal (pre-S2) domain of a hepatitis B virus surface glycoprotein is translocated across membranes by downstream signal sequences. Journal of Virology 64:1414–1419
    [Google Scholar]
  12. Gallina A., De Koning A., Rossi F., Calogero R., Manservigi R., Milanesi G. 1992; Translational modulation in hepatitis B virus preS-S open reading frame expression. Journal of General Virology 73:139–148
    [Google Scholar]
  13. Ganem D. 1991; Assembly of hepadnaviral virions and subviral particles. Current Topics in Microbiology and Immunology 168:61–83
    [Google Scholar]
  14. Ganem D., Varmus H. E. 1987; The molecular biology of the hepatitis B viruses. Annual Review of Biochemistry 56:651–693
    [Google Scholar]
  15. Gorman C. 1985; High efficiency gene transfer into mammalian cells. In DNA Cloning: A Practical Approach 2 pp. 143–190 Glover D. M. Edited by Oxford: IRL Press;
    [Google Scholar]
  16. Graham F. L., Smiley J., Russell W. C., Nairn R. 1977; Characteristics of a human cell line transformed by DNA from human adenovirus type 5. Journal of General Virology 36:59–72
    [Google Scholar]
  17. Heermann K. H., Goldmann U., Schwartz W., Seyffarth T., Baumgarten H., Gerlich W. H. 1984; Large surface proteins of hepatitis B virus containing the pre-s sequence. Journal of Virology 52:396–402
    [Google Scholar]
  18. Howard C., Frew A., D’Mello F., Stirk H. 1991; Structure of HBV preS protein predicted by peptide scanning and computer modeling. In Viral Hepatitis 1990 pp. 255–257 Hollinger F. B., Lemon S. M., Margolis H. S. Edited by Baltimore: Williams & Wilkins;
    [Google Scholar]
  19. Huovila A. J., Eder A. M., Fuller S. D. 1992; Hepatitis B surface antigen assembles in a post-ER, pre-Golgi compartment. Journal of Cell Biology 118:1305–1320
    [Google Scholar]
  20. Hurtley S. 1992; Golgi localization signals. Trends in Biochemical Sciences 17:2–3
    [Google Scholar]
  21. Klausner R., Sitia R. 1990; Protein degradation in the endoplasmic reticulum. Cell 62:611–614
    [Google Scholar]
  22. Kozak M. 1989; The scanning model for translation: an update. Journal of Cell Biology 108:229–241
    [Google Scholar]
  23. Kuroki K., Russnak R., Ganem D. 1989; Novel N-terminal amino acid sequence required for retention of a hepatitis B virus glycoprotein in the endoplasmic reticulum. Molecular and Cellular Biology 9:4459–1466
    [Google Scholar]
  24. Kuroki K., Floreani M., Mimms L., Ganem D. 1990; Epitope mapping of the preSl domain of the hepatitis B virus large surface protein. Virology 176:620–624
    [Google Scholar]
  25. McLachlan A., Milich D. R., Raney A. K., Riggs M. G., Hughes J. L., Sorge J., Chisari F. V. 1987; Expression of hepatitis B virus surface and core antigens: influences of pre-S and precore sequences. Journal of Virology 51:683–692
    [Google Scholar]
  26. MacRae D., Bruss V., Ganem D. 1991; Myristylation of a duck hepatitis B virus envelope protein is essential for infectivity but not for virus assembly. Virology 181:359–363
    [Google Scholar]
  27. Manservigi R., Grossi M. P., Gualandri R., Balboni P. G., Marchini A., Rotola A., Rimessi P., Di Luca D., Cassai E., Barbanti-Brodano G. 1990; Protection from herpes simplex virus type 1 lethal and latent infections by secreted recombinant glycoprotein B constitutively expressed in human cells with a BK virus episomal vector. Journal of Virology 64:431–136
    [Google Scholar]
  28. Ou J., Rutter W. J. 1987; Regulation of the hepatitis B virus major surface antigen by the preS-1 protein. Journal of Virology 61:782–786
    [Google Scholar]
  29. Patzer E., Nakamura G., Simonsen C., Levinson A., Brands R. 1986; Intracellular assembly and packaging of hepatitis B surface antigen particles occur in the endoplasmic reticulum. Journal of Virology 58:884–892
    [Google Scholar]
  30. Pelham H. 1989; Control of protein exit from the endoplasmic reticulum. Annual Review of Cell Biology 5:1–23
    [Google Scholar]
  31. Persing D. H., Varmus H. E., Ganem D. 1986; Inhibition of secretion of hepatitis B surface antigen by a related presurface polypeptide. Science 234:1388–1391
    [Google Scholar]
  32. Persing D. H., Varmus H. E., Ganem D. 1987; The preSl protein of hepatitis B virus is acylated at its amino terminus with myristic acid. Journal of Virology 61:1672–1677
    [Google Scholar]
  33. Peterson D. L. 1987; The structure of hepatitis B surface antigen and its antigenic sites. Bioessays 6:258–262
    [Google Scholar]
  34. Prange R., Clemen A., Streeck R. 1991; Myristylation is involved in intracellular retention of hepatitis B virus envelope proteins. Journal of Virology 65:3919–3923
    [Google Scholar]
  35. Prange R., Nagel R., Streeck R. 1992; Deletions in the hepatitis B virus small envelope protein: effect on assembly and secretion of surface antigen particles. Journal of Virology 66:5832–5841
    [Google Scholar]
  36. Rose J., Doms R. 1988; Regulation of protein export from the endoplasmic reticulum. Annual Review of Cell Biology 4:257–288
    [Google Scholar]
  37. Rothman J. E., Orci L. 1992; Molecular dissection of the secretory pathway. Nature; London: 355409–415
    [Google Scholar]
  38. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: A Laboratory Manual, 2nd edn. New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  39. Simon K., Lingappa V., Ganem D. 1988; Secreted hepatitis B surface antigen polypeptides are derived from a transmembrane precursor. Journal of Cell Biology 107:2163–2168
    [Google Scholar]
  40. Standring D. N., Ou J., Rutter W. J. 1986; Assembly of viral particles in Xenopus oocytes: pre-surface-antigens regulate secretion of the hepatitis B viral surface envelope particle. Proceedings of the National Academy of Sciences, U.S.A 83:9338–9342
    [Google Scholar]
  41. Stephens E. B., Compans R. W. 1988; Assembly of animal viruses at cellular membranes. Annual Review of Microbiology 42:489–516
    [Google Scholar]
  42. Yu X. 1991; The C-terminal half of the preSl region is essential for the secretion of human hepatitis B virus large S protein devoid of the N-terminal retention sequence. Virology 181:386–389
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-75-2-449
Loading
/content/journal/jgv/10.1099/0022-1317-75-2-449
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error