The Secretory Core Protein of Human Hepatitis B Virus is Expressed on the Cell Surface

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1989 Dec 1

PMID 2685356

Citations 36

Authors

H J Schlicht

H Schaller

Affiliations

Soon will be listed here.

Abstract

Human hepatitis B virus (HBV) causes acute and chronic liver disease, which can result in tumor formation. An as yet unexplained phenomenon is that virus elimination usually correlates with the development of antibodies directed against the HBeAg, a secretory HBV core gene product which can be detected in the serum of infected patients. Expression of HBeAg in a human hepatoma cell line by using recombinant vaccinia viruses revealed that the HBeAg is not only secreted from HBeAg-producing cells but also incorporated into the outer cell membrane. No membrane-expressed core gene product could be detected when the cytoplasmic core protein (HBcAg) was expressed. Immune sera from patients who developed anti-HBe antibodies efficiently recognized the membrane-bound HBeAg, suggesting that surface-expressed HBeAg can serve as a target for an antibody-mediated elimination of HBV-infected cells.

Citing Articles

Furin-mediated protein processing in infectious diseases and cancer.

Braun E, Sauter D Clin Transl Immunology. 2019; 8(8):e1073.

PMID: 31406574 PMC: 6682551. DOI: 10.1002/cti2.1073.

ADCC-Mediated CD56 NK Cell Responses Are Associated with Early HBsAg Clearance in Acute HBV Infection.

Yu W, Cosgrove C, Berger C, Cheney P, Krykbaeva M, Kim A Pathog Immun. 2018; 3(1):2-18.

PMID: 29541698 PMC: 5847299. DOI: 10.20411/pai.v3i1.228.

Predominance of precore mutations and clinical significance of basal core promoter mutations in chronic hepatitis B virus infection in Indonesia.

Juniastuti , Utsumi T, Aksono E, Yano Y, Soetjipto , Hayashi Y Biomed Rep. 2014; 1(4):522-528.

PMID: 24648979 PMC: 3917060. DOI: 10.3892/br.2013.106.

CD40 activation rescues antiviral CD8⁺ T cells from PD-1-mediated exhaustion.

Isogawa M, Chung J, Murata Y, Kakimi K, Chisari F PLoS Pathog. 2013; 9(7):e1003490.

PMID: 23853599 PMC: 3708877. DOI: 10.1371/journal.ppat.1003490.

Association of core promoter mutations of hepatitis B virus and viral load is different in HBeAg(+) and HBeAg(-) patients.

Utama A, Siburian M, Purwantomo S, Intan M, Kurniasih T, Gani R World J Gastroenterol. 2011; 17(6):708-16.

PMID: 21390140 PMC: 3042648. DOI: 10.3748/wjg.v17.i6.708.

References

Schlicht H, Salfeld J, Schaller H . 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. J Virol. 1987; 61(12):3701-9. PMC: 255982. DOI: 10.1128/JVI.61.12.3701-3709.1987. View

Bjorkman P, Saper M, Samraoui B, Bennett W, Strominger J, Wiley D . The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 1987; 329(6139):512-8. DOI: 10.1038/329512a0. View

Bruss V, Gerlich W . Formation of transmembraneous hepatitis B e-antigen by cotranslational in vitro processing of the viral precore protein. Virology. 1988; 163(2):268-75. DOI: 10.1016/0042-6822(88)90266-8. View

Garcia P, Ou J, Rutter W, 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; 106(4):1093-104. PMC: 2114996. DOI: 10.1083/jcb.106.4.1093. View

Standring D, Ou J, Masiarz F, Rutter W . 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; 85(22):8405-9. PMC: 282466. DOI: 10.1073/pnas.85.22.8405. View

Salfeld J, Pfaff E, Noah M, Schaller H . Antigenic determinants and functional domains in core antigen and e antigen from hepatitis B virus. J Virol. 1989; 63(2):798-808. PMC: 247753. DOI: 10.1128/JVI.63.2.798-808.1989. View

Levrero M, Will H, Perricaudet M, Rossignol J . Expression mechanism of the hepatitis B virus (HBV) C gene and biosynthesis of HBe antigen. Virology. 1989; 170(1):99-106. DOI: 10.1016/0042-6822(89)90356-5. View

Magnius L, ESPMARK J . New specificities in Australia antigen positive sera distinct from the Le Bouvier determinants. J Immunol. 1972; 109(5):1017-21. View

Ledbetter J, Nowinski R, Emery S . Viral proteins expressed on the surface of murine leukemia cells. J Virol. 1977; 22(1):65-73. PMC: 515686. DOI: 10.1128/JVI.22.1.65-73.1977. View

10.

Edwards S, Fan H . gag-Related polyproteins of Moloney murine leukemia virus: evidence for independent synthesis of glycosylated and unglycosylated forms. J Virol. 1979; 30(2):551-63. PMC: 353359. DOI: 10.1128/JVI.30.2.551-563.1979. View

11.

Aden D, FOGEL A, Plotkin S, Damjanov I, Knowles B . Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line. Nature. 1979; 282(5739):615-6. DOI: 10.1038/282615a0. View

12.

Takahashi K, Machida A, Funatsu G, Nomura M, Usuda S, Aoyagi S . Immunochemical structure of hepatitis B e antigen in the serum. J Immunol. 1983; 130(6):2903-7. View

13.

Murray K, Bruce S, Hinnen A, Wingfield P, van Erd P, de Reus A . Hepatitis B virus antigens made in microbial cells immunise against viral infection. EMBO J. 1984; 3(3):645-50. PMC: 557401. DOI: 10.1002/j.1460-2075.1984.tb01861.x. View

14.

Stephan W, Prince A, Brotman B . Modulation of hepatitis B infection by intravenous application of an immunoglobulin preparation that contains antibodies to hepatitis B e and core antigens but not to hepatitis B surface antigen. J Virol. 1984; 51(2):420-4. PMC: 254454. DOI: 10.1128/JVI.51.2.420-424.1984. View

15.

Kieny M, Lathe R, Drillien R, Spehner D, Skory S, Schmitt D . Expression of rabies virus glycoprotein from a recombinant vaccinia virus. Nature. 1984; 312(5990):163-6. DOI: 10.1038/312163a0. View

16.

Zoller M, Smith M . Oligonucleotide-directed mutagenesis: a simple method using two oligonucleotide primers and a single-stranded DNA template. DNA. 1984; 3(6):479-88. DOI: 10.1089/dna.1.1984.3.479. View

17.

Pillemer E, Kooistra D, Witte O, Weissman I . Monoclonal antibody to the amino-terminal L sequence of murine leukemia virus glycosylated gag polyproteins demonstrates their unusual orientation in the cell membrane. J Virol. 1986; 57(2):413-21. PMC: 252752. DOI: 10.1128/JVI.57.2.413-421.1986. View

18.

Ou J, Laub O, Rutter W . 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; 83(6):1578-82. PMC: 323126. DOI: 10.1073/pnas.83.6.1578. View

19.

Townsend A, Rothbard J, Gotch F, Bahadur G, Wraith D, McMichael A . The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986; 44(6):959-68. DOI: 10.1016/0092-8674(86)90019-x. View

20.

Chakrabarti S, Brechling K, Moss B . Vaccinia virus expression vector: coexpression of beta-galactosidase provides visual screening of recombinant virus plaques. Mol Cell Biol. 1985; 5(12):3403-9. PMC: 369169. DOI: 10.1128/mcb.5.12.3403-3409.1985. View