Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1991 Sep;65(9):5080–5083. doi: 10.1128/jvi.65.9.5080-5083.1991

Proteolytic conversion of hepatitis B virus e antigen precursor to end product occurs in a postendoplasmic reticulum compartment.

J Wang 1, A S Lee 1, J H Ou 1
PMCID: PMC248973  PMID: 1870212

Abstract

At least two proteolytic events are involved in the biogenesis of hepatitis B virus e antigen. The first proteolytic event removes the signal peptide and results in the translocation of the precursor protein, P22, into the lumen of the endoplasmic reticulum (ER). The second proteolytic event removes the carboxy-terminal arginine-rich sequence of P22 and converts it to the 16-kDa hepatitis B virus e antigen end product. In contrast to the first proteolytic event, the second proteolytic event is suppressed by brefeldin A, a chemical that inhibits the transport of protein from the ER to the Golgi apparatus. In subcellular fractionation experiments, P22 was detected in both the ER and the Golgi fractions, but P16 was detected only in the Golgi fraction. On the basis of these results, we conclude that the conversion of P22 to P16 occurs ina post-ER compartment, mostly likely the Golgi apparatus.

Full text

PDF
5080

Images in this article

5081Image
on p.5081
5081Image
on p.5081
5082Image
on p.5082
5083Image
on p.5083

Selected References

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

  1. Bole D. G., Hendershot L. M., Kearney J. F. Posttranslational association of immunoglobulin heavy chain binding protein with nascent heavy chains in nonsecreting and secreting hybridomas. J Cell Biol. 1986 May;102(5):1558–1566. doi: 10.1083/jcb.102.5.1558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bruss V., Gerlich W. H. Formation of transmembraneous hepatitis B e-antigen by cotranslational in vitro processing of the viral precore protein. Virology. 1988 Apr;163(2):268–275. doi: 10.1016/0042-6822(88)90266-8. [DOI] [PubMed] [Google Scholar]
  3. Ganem D., Varmus H. E. The molecular biology of the hepatitis B viruses. Annu Rev Biochem. 1987;56:651–693. doi: 10.1146/annurev.bi.56.070187.003251. [DOI] [PubMed] [Google Scholar]
  4. Garcia P. D., Ou J. H., Rutter W. J., Walter P. Targeting of the hepatitis B virus precore protein to the endoplasmic reticulum membrane: after signal peptide cleavage translocation can be aborted and the product released into the cytoplasm. J Cell Biol. 1988 Apr;106(4):1093–1104. doi: 10.1083/jcb.106.4.1093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hendershot L. M., Ting J., Lee A. S. Identity of the immunoglobulin heavy-chain-binding protein with the 78,000-dalton glucose-regulated protein and the role of posttranslational modifications in its binding function. Mol Cell Biol. 1988 Oct;8(10):4250–4256. doi: 10.1128/mcb.8.10.4250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Junker M., Galle P., Schaller H. Expression and replication of the hepatitis B virus genome under foreign promoter control. Nucleic Acids Res. 1987 Dec 23;15(24):10117–10132. doi: 10.1093/nar/15.24.10117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kelly R. B. Pathways of protein secretion in eukaryotes. Science. 1985 Oct 4;230(4721):25–32. doi: 10.1126/science.2994224. [DOI] [PubMed] [Google Scholar]
  8. Li X. A., Warren D. W., Gregoire J., Pedersen R. C., Lee A. S. The rat 78,000 dalton glucose-regulated protein (GRP78) as a precursor for the rat steroidogenesis-activator polypeptide (SAP): the SAP coding sequence is homologous with the terminal end of GRP78. Mol Endocrinol. 1989 Dec;3(12):1944–1952. doi: 10.1210/mend-3-12-1944. [DOI] [PubMed] [Google Scholar]
  9. Lippincott-Schwartz J., Yuan L. C., Bonifacino J. S., Klausner R. D. Rapid redistribution of Golgi proteins into the ER in cells treated with brefeldin A: evidence for membrane cycling from Golgi to ER. Cell. 1989 Mar 10;56(5):801–813. doi: 10.1016/0092-8674(89)90685-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Misumi Y., Misumi Y., Miki K., Takatsuki A., Tamura G., Ikehara Y. Novel blockade by brefeldin A of intracellular transport of secretory proteins in cultured rat hepatocytes. J Biol Chem. 1986 Aug 25;261(24):11398–11403. [PubMed] [Google Scholar]
  11. Nakaki T., Deans R. J., Lee A. S. Enhanced transcription of the 78,000-dalton glucose-regulated protein (GRP78) gene and association of GRP78 with immunoglobulin light chains in a nonsecreting B-cell myeloma line (NS-1). Mol Cell Biol. 1989 May;9(5):2233–2238. doi: 10.1128/mcb.9.5.2233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nielsen J. O., Dietrichson O., Juhl E. Incidence and meaning of the "e" determinant among hepatitis-B-antigen positive patients with acute and chronic liver diseases. Report from the Copenhagen Hepatitis Acuta Programme. Lancet. 1974 Oct 19;2(7886):913–915. doi: 10.1016/s0140-6736(74)91127-1. [DOI] [PubMed] [Google Scholar]
  13. Ou J. H., Laub O., Rutter W. J. Hepatitis B virus gene function: the precore region targets the core antigen to cellular membranes and causes the secretion of the e antigen. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1578–1582. doi: 10.1073/pnas.83.6.1578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ou J. H., Yeh C. T., Yen T. S. Transport of hepatitis B virus precore protein into the nucleus after cleavage of its signal peptide. J Virol. 1989 Dec;63(12):5238–5243. doi: 10.1128/jvi.63.12.5238-5243.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Roossinck M. J., Jameel S., Loukin S. H., Siddiqui A. Expression of hepatitis B viral core region in mammalian cells. Mol Cell Biol. 1986 May;6(5):1393–1400. doi: 10.1128/mcb.6.5.1393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Serafini T., Stenbeck G., Brecht A., Lottspeich F., Orci L., Rothman J. E., Wieland F. T. A coat subunit of Golgi-derived non-clathrin-coated vesicles with homology to the clathrin-coated vesicle coat protein beta-adaptin. Nature. 1991 Jan 17;349(6306):215–220. doi: 10.1038/349215a0. [DOI] [PubMed] [Google Scholar]
  17. Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
  18. Standring D. N., Ou J. H., Masiarz F. R., Rutter W. J. A signal peptide encoded within the precore region of hepatitis B virus directs the secretion of a heterogeneous population of e antigens in Xenopus oocytes. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8405–8409. doi: 10.1073/pnas.85.22.8405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Takahashi K., Imai M., Tsuda F., Takahashi T., Miyakawa Y. Association of dane particles with e antigen in the serum of asymptomatic carriers of hepatitis B surface antigen. J Immunol. 1976 Jul;117(1):102–105. [PubMed] [Google Scholar]
  20. Tartakoff A. M., Vassalli P. Lectin-binding sites as markers of Golgi subcompartments: proximal-to-distal maturation of oligosaccharides. J Cell Biol. 1983 Oct;97(4):1243–1248. doi: 10.1083/jcb.97.4.1243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Weimer T., Salfeld J., Will H. Expression of the hepatitis B virus core gene in vitro and in vivo. J Virol. 1987 Oct;61(10):3109–3113. doi: 10.1128/jvi.61.10.3109-3113.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Yeh C. T., Ou J. H. Phosphorylation of hepatitis B virus precore and core proteins. J Virol. 1991 May;65(5):2327–2331. doi: 10.1128/jvi.65.5.2327-2331.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES