Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1988 Dec 1;107(6):2163–2168. doi: 10.1083/jcb.107.6.2163

Secreted hepatitis B surface antigen polypeptides are derived from a transmembrane precursor

PMCID: PMC2115684  PMID: 3198683

Abstract

Hepatitis B surface antigen (HBsAg), the major coat protein of hepatitis B virus, is also independently secreted from infected cells as a lipoprotein particle. Secretion proceeds without signal sequence removal or cleavage of other segments of the polypeptide. We have examined the synthesis and transport of HBsAg in cultured cells expressing the cloned surface antigen gene. Our results show that HBsAg is initially synthesized as a integral membrane protein. This transmembrane form is slowly converted to a secreted lipoprotein complex in the lumen of the endoplasmic reticulum via a series of definable intermediates, after which it is secreted from the cell. This unusual export process shares many features with the assembly and budding reactions of conventional enveloped animal viruses. However, it differs importantly in its absence of a requirement for the participation of nucleocapsid or other viral proteins.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blobel G., Dobberstein B. Transfer of proteins across membranes. II. Reconstitution of functional rough microsomes from heterologous components. J Cell Biol. 1975 Dec;67(3):852–862. doi: 10.1083/jcb.67.3.852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blobel G. Intracellular protein topogenesis. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1496–1500. doi: 10.1073/pnas.77.3.1496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Derynck R., Jarrett J. A., Chen E. Y., Goeddel D. V. The murine transforming growth factor-beta precursor. J Biol Chem. 1986 Apr 5;261(10):4377–4379. [PubMed] [Google Scholar]
  4. Dubois M. F., Pourcel C., Rousset S., Chany C., Tiollais P. Excretion of hepatitis B surface antigen particles from mouse cells transformed with cloned viral DNA. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4549–4553. doi: 10.1073/pnas.77.8.4549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Eble B. E., Lingappa V. R., Ganem D. Hepatitis B surface antigen: an unusual secreted protein initially synthesized as a transmembrane polypeptide. Mol Cell Biol. 1986 May;6(5):1454–1463. doi: 10.1128/mcb.6.5.1454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eble B. E., MacRae D. R., Lingappa V. R., Ganem D. Multiple topogenic sequences determine the transmembrane orientation of the hepatitis B surface antigen. Mol Cell Biol. 1987 Oct;7(10):3591–3601. doi: 10.1128/mcb.7.10.3591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fuller S. D. The T=4 envelope of Sindbis virus is organized by interactions with a complementary T=3 capsid. Cell. 1987 Mar 27;48(6):923–934. doi: 10.1016/0092-8674(87)90701-x. [DOI] [PubMed] [Google Scholar]
  8. Gavilanes F., Gonzalez-Ros J. M., Peterson D. L. Structure of hepatitis B surface antigen. Characterization of the lipid components and their association with the viral proteins. J Biol Chem. 1982 Jul 10;257(13):7770–7777. [PubMed] [Google Scholar]
  9. Gerber M. A., Hadziyannis S., Vissoulis C., Schaffner F., Paronetto F., Popper H. Electron microscopy and immunoelectronmicroscopy of cytoplasmic hepatitis B antigen in hepatocytes. Am J Pathol. 1974 Jun;75(3):489–502. [PMC free article] [PubMed] [Google Scholar]
  10. Gray A., Dull T. J., Ullrich A. Nucleotide sequence of epidermal growth factor cDNA predicts a 128,000-molecular weight protein precursor. Nature. 1983 Jun 23;303(5919):722–725. doi: 10.1038/303722a0. [DOI] [PubMed] [Google Scholar]
  11. Laub O., Rall L. B., Truett M., Shaul Y., Standring D. N., Valenzuela P., Rutter W. J. Synthesis of hepatitis B surface antigen in mammalian cells: expression of the entire gene and the coding region. J Virol. 1983 Oct;48(1):271–280. doi: 10.1128/jvi.48.1.271-280.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lee D. C., Rose T. M., Webb N. R., Todaro G. J. Cloning and sequence analysis of a cDNA for rat transforming growth factor-alpha. Nature. 1985 Feb 7;313(6002):489–491. doi: 10.1038/313489a0. [DOI] [PubMed] [Google Scholar]
  13. Liu C. C., Yansura D., Levinson A. D. Direct expression of hepatitis B surface antigen in monkey cells from an SV40 vector. DNA. 1982;1(3):213–221. doi: 10.1089/dna.1.1982.1.213. [DOI] [PubMed] [Google Scholar]
  14. Moriarty A. M., Hoyer B. H., Shih J. W., Gerin J. L., Hamer D. H. Expression of the hepatitis B virus surface antigen gene in cell culture by using a simian virus 40 vector. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2606–2610. doi: 10.1073/pnas.78.4.2606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mostov K. E., Blobel G. A transmembrane precursor of secretory component. The receptor for transcellular transport of polymeric immunoglobulins. J Biol Chem. 1982 Oct 10;257(19):11816–11821. [PubMed] [Google Scholar]
  16. Patzer E. J., Nakamura G. R., Simonsen C. C., Levinson A. D., Brands R. Intracellular assembly and packaging of hepatitis B surface antigen particles occur in the endoplasmic reticulum. J Virol. 1986 Jun;58(3):884–892. doi: 10.1128/jvi.58.3.884-892.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Patzer E. J., Nakamura G. R., Yaffe A. Intracellular transport and secretion of hepatitis B surface antigen in mammalian cells. J Virol. 1984 Aug;51(2):346–353. doi: 10.1128/jvi.51.2.346-353.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Persing D. H., Varmus H. E., Ganem D. A frameshift mutation in the pre-S region of the human hepatitis B virus genome allows production of surface antigen particles but eliminates binding to polymerized albumin. Proc Natl Acad Sci U S A. 1985 May;82(10):3440–3444. doi: 10.1073/pnas.82.10.3440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Persing D. H., Varmus H. E., Ganem D. Inhibition of secretion of hepatitis B surface antigen by a related presurface polypeptide. Science. 1986 Dec 12;234(4782):1388–1391. doi: 10.1126/science.3787251. [DOI] [PubMed] [Google Scholar]
  20. Peterson D. L., Roberts I. M., Vyas G. N. Partial amino acid sequence of two major component polypeptides of hepatitis B surface antigen. Proc Natl Acad Sci U S A. 1977 Apr;74(4):1530–1534. doi: 10.1073/pnas.74.4.1530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Scott J., Urdea M., Quiroga M., Sanchez-Pescador R., Fong N., Selby M., Rutter W. J., Bell G. I. Structure of a mouse submaxillary messenger RNA encoding epidermal growth factor and seven related proteins. Science. 1983 Jul 15;221(4607):236–240. doi: 10.1126/science.6602382. [DOI] [PubMed] [Google Scholar]
  22. Simon K., Lingappa V. R., Ganem D. A block to the intracellular transport and assembly of hepatitis B surface antigen polypeptides in Xenopus oocytes. Virology. 1988 Sep;166(1):76–81. doi: 10.1016/0042-6822(88)90148-1. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES