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Journal of Virology logoLink to Journal of Virology
. 1986 Dec;60(3):880–887. doi: 10.1128/jvi.60.3.880-887.1986

Expression of hepatitis B virus large envelope polypeptide inhibits hepatitis B surface antigen secretion in transgenic mice.

F V Chisari, P Filippi, A McLachlan, D R Milich, M Riggs, S Lee, R D Palmiter, C A Pinkert, R L Brinster
PMCID: PMC253312  PMID: 3783819

Abstract

The outer membrane of the hepatitis B virus consists of host lipid and the hepatitis B virus major (p25, gp28), middle (gp33, gp36), and large (p39, gp42) envelope polypeptides. These polypeptides are encoded by a large open reading frame that contains three in-phase translation start codons and a shared termination signal. The influence of the large envelope polypeptide on the secretion of hepatitis B surface antigen (HBsAg) subviral particles in transgenic mice was examined. The major polypeptide is the dominant structural component of the HBsAg particles, which are readily secreted into the blood. A relative increase in production of the large envelope polypeptide compared with that of the major envelope polypeptide led to profound reduction of the HBsAg concentration in serum as a result of accumulation of both envelope polypeptides in a relatively insoluble compartment within the cell. We conclude that inhibition of HBsAg secretion is related to a hitherto unknown property of the pre-S-containing domain of the large envelope polypeptide.

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Selected References

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  1. Babinet C., Farza H., Morello D., Hadchouel M., Pourcel C. Specific expression of hepatitis B surface antigen (HBsAg) in transgenic mice. Science. 1985 Dec 6;230(4730):1160–1163. doi: 10.1126/science.3865370. [DOI] [PubMed] [Google Scholar]
  2. Cattaneo R., Will H., Hernandez N., Schaller H. Signals regulating hepatitis B surface antigen transcription. Nature. 1983 Sep 22;305(5932):336–338. doi: 10.1038/305336a0. [DOI] [PubMed] [Google Scholar]
  3. Chisari F. V., Pinkert C. A., Milich D. R., Filippi P., McLachlan A., Palmiter R. D., Brinster R. L. A transgenic mouse model of the chronic hepatitis B surface antigen carrier state. Science. 1985 Dec 6;230(4730):1157–1160. doi: 10.1126/science.3865369. [DOI] [PubMed] [Google Scholar]
  4. Dunn A. E., Peters R. L., Schweitzer I. L. An ultrastructural study of liver explants from infants with vertically transmitted hepatitis. Exp Mol Pathol. 1973 Aug;19(1):113–126. doi: 10.1016/0014-4800(73)90045-2. [DOI] [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. Galibert F., Mandart E., Fitoussi F., Tiollais P., Charnay P. Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature. 1979 Oct 25;281(5733):646–650. doi: 10.1038/281646a0. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Gerin J. L., Alexander H., Shih J. W., Purcell R. H., Dapolito G., Engle R., Green N., Sutcliffe J. G., Shinnick T. M., Lerner R. A. Chemically synthesized peptides of hepatitis B surface antigen duplicate the d/y specificities and induce subtype-specific antibodies in chimpanzees. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2365–2369. doi: 10.1073/pnas.80.8.2365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Heermann K. H., Goldmann U., Schwartz W., Seyffarth T., Baumgarten H., Gerlich W. H. Large surface proteins of hepatitis B virus containing the pre-s sequence. J Virol. 1984 Nov;52(2):396–402. doi: 10.1128/jvi.52.2.396-402.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kamimura T., Yoshikawa A., Ichida F., Sasaki H. Electron microscopic studies of Dane particles in hepatocytes with special reference to intracellular development of Dane particles and their relation with HBeAg in serum. Hepatology. 1981 Sep-Oct;1(5):392–397. doi: 10.1002/hep.1840010504. [DOI] [PubMed] [Google Scholar]
  11. Klinkert M. Q., Theilmann L., Pfaff E., Schaller H. Pre-S1 antigens and antibodies early in the course of acute hepatitis B virus infection. J Virol. 1986 May;58(2):522–525. doi: 10.1128/jvi.58.2.522-525.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Michel M. L., Pontisso P., Sobczak E., Malpièce Y., Streeck R. E., Tiollais P. Synthesis in animal cells of hepatitis B surface antigen particles carrying a receptor for polymerized human serum albumin. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7708–7712. doi: 10.1073/pnas.81.24.7708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Milich D. R., McLachlan A., Chisari F. V., Kent S. B., Thorton G. B. Immune response to the pre-S(1) region of the hepatitis B surface antigen (HBsAg): a pre-S(1)-specific T cell response can bypass nonresponsiveness to the pre-S(2) and S regions of HBsAg. J Immunol. 1986 Jul 1;137(1):315–322. [PubMed] [Google Scholar]
  14. Milich D. R., Thornton G. B., Neurath A. R., Kent S. B., Michel M. L., Tiollais P., Chisari F. V. Enhanced immunogenicity of the pre-S region of hepatitis B surface antigen. Science. 1985 Jun 7;228(4704):1195–1199. doi: 10.1126/science.2408336. [DOI] [PubMed] [Google Scholar]
  15. Moriarty A. M., Alexander H., Lerner R. A., Thornton G. B. Antibodies to peptides detect new hepatitis B antigen: serological correlation with hepatocellular carcinoma. Science. 1985 Jan 25;227(4685):429–433. doi: 10.1126/science.2981434. [DOI] [PubMed] [Google Scholar]
  16. Neurath A. R., Kent S. B., Strick N. Location and chemical synthesis of a pre-S gene coded immunodominant epitope of hepatitis B virus. Science. 1984 Apr 27;224(4647):392–395. doi: 10.1126/science.6200931. [DOI] [PubMed] [Google Scholar]
  17. Neurath A. R., Kent S. B., Strick N., Taylor P., Stevens C. E. Hepatitis B virus contains pre-S gene-encoded domains. Nature. 1985 May 9;315(6015):154–156. doi: 10.1038/315154a0. [DOI] [PubMed] [Google Scholar]
  18. Okamoto H., Imai M., Usuda S., Tanaka E., Tachibana K., Mishiro S., Machida A., Nakamura T., Miyakawa Y., Mayumi M. Hemagglutination assay of polypeptide coded by the pre-S region of hepatitis B virus DNA with monoclonal antibody: correlation of pre-S polypeptide with the receptor for polymerized human serum albumin in serums containing hepatitis B antigens. J Immunol. 1985 Feb;134(2):1212–1216. [PubMed] [Google Scholar]
  19. Ou J., Rutter W. J. Hybrid hepatitis B virus-host transcripts in a human hepatoma cell. Proc Natl Acad Sci U S A. 1985 Jan;82(1):83–87. doi: 10.1073/pnas.82.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. 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]
  23. Pfaff E., Klinkert M. Q., Theilmann L., Schaller H. Characterization of large surface proteins of hepatitis B virus by antibodies to preS-S encoded amino acids. Virology. 1986 Jan 15;148(1):15–22. doi: 10.1016/0042-6822(86)90399-5. [DOI] [PubMed] [Google Scholar]
  24. Schaeffer E., Snyder R. L., Sninsky J. J. Identification and localization of pre-s-encoded polypeptides from woodchuck and ground squirrel hepatitis viruses. J Virol. 1986 Jan;57(1):173–182. doi: 10.1128/jvi.57.1.173-182.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Siddiqui A., Jameel S., Mapoles J. Transcriptional control elements of hepatitis B surface antigen gene. Proc Natl Acad Sci U S A. 1986 Feb;83(3):566–570. doi: 10.1073/pnas.83.3.566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Standring D. N., Rutter W. J., Varmus H. E., Ganem D. Transcription of the hepatitis B surface antigen gene in cultured murine cells initiates within the presurface region. J Virol. 1984 May;50(2):563–571. doi: 10.1128/jvi.50.2.563-571.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Stibbe W., Gerlich W. H. Characterization of pre-s gene products in hepatitis B surface antigen. Dev Biol Stand. 1983;54:33–43. [PubMed] [Google Scholar]
  28. Takahashi K., Kishimoto S., Ohnuma H., Machida A., Takai E., Tsuda F., Miyamoto H., Tanaka T., Matsushita K., Oda K. Polypeptides coded for by the region pre-S and gene S of hepatitis B virus DNA with the receptor for polymerized human serum albumin: expression on hepatitis B particles produced in the HBeAg or anti-HBe phase of hepatitis B virus infection. J Immunol. 1986 May 1;136(9):3467–3472. [PubMed] [Google Scholar]
  29. Theilmann L., Klinkert M. Q., Gmelin K., Salfeld J., Schaller H., Pfaff E. Detection of pre-S1 proteins in serum and liver of HBsAg-positive patients: a new marker for hepatitis B virus infection. Hepatology. 1986 Mar-Apr;6(2):186–190. doi: 10.1002/hep.1840060206. [DOI] [PubMed] [Google Scholar]
  30. Tiollais P., Pourcel C., Dejean A. The hepatitis B virus. Nature. 1985 Oct 10;317(6037):489–495. doi: 10.1038/317489a0. [DOI] [PubMed] [Google Scholar]
  31. Yamada G., Feinberg L. E., Nakane P. K. Hepatitis B. Cytologic localization of virus antigens and the role of the immune response. Hum Pathol. 1978 Jan;9(1):93–109. doi: 10.1016/s0046-8177(78)80011-2. [DOI] [PubMed] [Google Scholar]

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