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. 1992 Nov;33(11):1544–1548. doi: 10.1136/gut.33.11.1544

Intrahepatic expression of pre-S1 and pre-S2 antigens in chronic hepatitis B virus infection in relation to hepatitis B virus replication and hepatitis delta virus superinfection.

C M Chu 1, Y F Liaw 1
PMCID: PMC1379543  PMID: 1452081

Abstract

Hepatocyte expression of pre-S1 and pre-S2 in relation to hepatitis B virus replication (hepatitis B virus-DNA in serum and HBcAg in the liver), histological activity and hepatitis delta virus superinfection was studied by indirect immunofluorescence on frozen sections of liver specimens from 68 patients with chronic hepatitis B virus infection. All 44 patients with chronic type B hepatitis had pre-S1 and pre-S2 display in the liver. The distribution of pre-S1 in the liver was membranous in one, mixed membranous and cytoplasmic in 12, and cytoplasmic in 31. The distribution of pre-S2 was membranous in one, mixed membranous and cytoplasmic in 26, and cytoplasmic in 17. Membranous expression of pre-S1 was significantly more prevalent in patients with active hepatitis B virus replication than in those without (13/28 v 0/16, p < 0.001), regardless of the histological activity, as was membranous expression of pre-S2 (27/28 v 0/16, p < 0.001). In contrast, a significantly higher extent of cytoplasmic expression of pre-S1 and pre-S2 was noted in patients without active hepatitis B virus replication than in those with. Of 24 patients with chronic type D hepatitis virus, eight had active hepatitis B virus replication, and the other 16 did not. The distribution and quantitative expression of pre-S1 and pre-S2 in the liver in these patients also correlated significantly with the status of hepatitis B virus replication and, moreover, showed little or no difference from those without hepatitis delta virus infection. In conclusion, all patients with chronic type B hepatitis had synthesis and display of pre-S1 and pre-S2 in the liver. The distribution and quantitative expression of pre-S1 and pre-S2, however, were closely related to the status of hepatitis B virus replication, but not to the histological activity. Hepatocyte expression of pre-S1 and pre-S2 in chronic type D hepatitis also correlated significantly with status of hepatitis B virus replication, and was not modulated by concurrent hepatitis delta virus infection.

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Selected References

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

  1. 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]
  2. Chu C. M., Liaw Y. F. Intrahepatic distribution of hepatitis B surface and core antigens in chronic hepatitis B virus infection. Hepatocyte with cytoplasmic/membranous hepatitis B core antigen as a possible target for immune hepatocytolysis. Gastroenterology. 1987 Jan;92(1):220–225. doi: 10.1016/0016-5085(87)90863-8. [DOI] [PubMed] [Google Scholar]
  3. Chu C. M., Liaw Y. F., Sheen I. S., Chen T. J. Intrahepatic expression of HBcAg and delta antigen in anti-HBe positive HBsAg carriers with acute exacerbation or chronic active liver disease. J Med Virol. 1990 Mar;30(3):181–186. doi: 10.1002/jmv.1890300307. [DOI] [PubMed] [Google Scholar]
  4. Dienes H. P., Gerlich W. H., Wörsdörfer M., Gerken G., Bianchi L., Hess G., Meyer zum Büschenfelde K. H. Hepatic expression patterns of the large and middle hepatitis B virus surface proteins in viremic and nonviremic chronic hepatitis B. Gastroenterology. 1990 Apr;98(4):1017–1023. doi: 10.1016/0016-5085(90)90028-y. [DOI] [PubMed] [Google Scholar]
  5. Fraiese A., Pontisso P., Cavalletto D., Fattovich G., Alberti A. Expression of preS1 and preS2 in the liver of chronic hepatitis B virus carriers. J Hepatol. 1988 Oct;7(2):157–163. doi: 10.1016/s0168-8278(88)80477-x. [DOI] [PubMed] [Google Scholar]
  6. Gerken G., Manns M., Gerlich W. H., Hess G., Meyer zum Büschenfelde K. H. Pre-S encoded surface proteins in relation to the major viral surface antigen in acute hepatitis B virus infection. Gastroenterology. 1987 Jun;92(6):1864–1868. doi: 10.1016/0016-5085(87)90617-2. [DOI] [PubMed] [Google Scholar]
  7. Hadziyannis S. J., Georgopoulou U., Psalidaki E., Budkowska A. Pre-S1 and Pre-S2 gene-encoded proteins in liver and serum in chronic hepatitis delta infection. J Med Virol. 1991 May;34(1):14–19. doi: 10.1002/jmv.1890340104. [DOI] [PubMed] [Google Scholar]
  8. Hadziyannis S. J., Sherman M., Lieberman H. M., Shafritz D. A. Liver disease activity and hepatitis B virus replication in chronic delta antigen-positive hepatitis B virus carriers. Hepatology. 1985 Jul-Aug;5(4):544–547. doi: 10.1002/hep.1840050404. [DOI] [PubMed] [Google Scholar]
  9. Hadziyannis S., Raimondo G., Papaioannou C., Anastassakos C., Wong D., Sninsky J., Shafritz D. Expression of pre-S gene-encoded proteins in liver and serum during chronic hepatitis B virus infection in comparison to other markers of active virus replication. J Hepatol. 1987 Dec;5(3):253–259. doi: 10.1016/s0168-8278(87)80029-6. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Hess G., Gerlich H., Gerken G., Manns M., Meyer Zum Büschenfelde K. H. Relationship of pre-S encoded antigens in liver and clinical manifestations of chronic hepatitis B infection. Liver. 1987 Oct;7(5):245–250. doi: 10.1111/j.1600-0676.1987.tb00352.x. [DOI] [PubMed] [Google Scholar]
  12. Hu K. Q., Hao L. J., Zhang Y. Y., Wang Y. K. Intrahepatic expression of pre-S proteins of hepatitis B virus and its possible relation to liver cell necrosis. Am J Gastroenterol. 1989 Dec;84(12):1538–1542. [PubMed] [Google Scholar]
  13. Hu K. Q., Yu Z. Q., Li F. H., Hao L. J. Expression and clinical significance of pre-S1 and S2 proteins of HBV in sera of patients with chronic liver disease. Liver. 1989 Jun;9(3):146–152. doi: 10.1111/j.1600-0676.1989.tb00391.x. [DOI] [PubMed] [Google Scholar]
  14. Ibarra M. Z., Mora I., Bartolomé J., Porres J. C., Carreño V. Detection of proteins encoded by the pre-S region of hepatitis B virus in the sera of HBsAg carriers: relation to viral replication. Liver. 1989 Jun;9(3):153–158. doi: 10.1111/j.1600-0676.1989.tb00392.x. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Kurai K., Iino S., Koike K., Mitamura K., Endo Y., Oka H. Serum titers of pre-S(2) antigen in patients with acute and chronic type B hepatitis: relation to serum aminotransferase activity and other hepatitis B virus markers. Hepatology. 1989 Feb;9(2):175–179. doi: 10.1002/hep.1840090202. [DOI] [PubMed] [Google Scholar]
  17. Liaw Y. F., Pao C. C., Chu C. M., Sheen I. S., Huang M. J. Changes of serum hepatitis B virus DNA in two types of clinical events preceding spontaneous hepatitis B e antigen seroconversion in chronic type B hepatitis. Hepatology. 1987 Jan-Feb;7(1):1–3. doi: 10.1002/hep.1840070102. [DOI] [PubMed] [Google Scholar]
  18. Mondelli M., Vergani G. M., Alberti A., Vergani D., Portmann B., Eddleston A. L., Williams R. Specificity of T lymphocyte cytotoxicity to autologous hepatocytes in chronic hepatitis B virus infection: evidence that T cells are directed against HBV core antigen expressed on hepatocytes. J Immunol. 1982 Dec;129(6):2773–2778. [PubMed] [Google Scholar]
  19. Neurath A. R., Jameson B. A., Huima T. Hepatitis B virus proteins eliciting protective immunity. Microbiol Sci. 1987 Feb;4(2):45–51. [PubMed] [Google Scholar]
  20. Neurath A. R., Kent S. B., Strick N., Parker K. Identification and chemical synthesis of a host cell receptor binding site on hepatitis B virus. Cell. 1986 Aug 1;46(3):429–436. doi: 10.1016/0092-8674(86)90663-x. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. 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]
  23. Rizzetto M., Canese M. G., Gerin J. L., London W. T., Sly D. L., Purcell R. H. Transmission of the hepatitis B virus-associated delta antigen to chimpanzees. J Infect Dis. 1980 May;141(5):590–602. doi: 10.1093/infdis/141.5.590. [DOI] [PubMed] [Google Scholar]
  24. Robinson W. S., Klote L., Aoki N. Hepadnaviruses in cirrhotic liver and hepatocellular carcinoma. J Med Virol. 1990 May;31(1):18–32. doi: 10.1002/jmv.1890310106. [DOI] [PubMed] [Google Scholar]
  25. Rodriguez Boulan E., Sabatini D. D. Asymmetric budding of viruses in epithelial monlayers: a model system for study of epithelial polarity. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5071–5075. doi: 10.1073/pnas.75.10.5071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Saito T., Kamimura T., Asakura H., Ishikawa M. Ultrastructural localization of Pre-S2 polypeptides in the liver tissues of patients with chronic hepatitis B virus infection. Liver. 1989 Dec;9(6):329–337. doi: 10.1111/j.1600-0676.1989.tb00420.x. [DOI] [PubMed] [Google Scholar]
  27. Standring D. N., Ou J. H., Rutter W. J. Assembly of viral particles in Xenopus oocytes: pre-surface-antigens regulate secretion of the hepatitis B viral surface envelope particle. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9338–9342. doi: 10.1073/pnas.83.24.9338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Suzuki K., Uchida T., Shikata T., Moriyama M., Arakawa Y., Mizokami M., Mima F. Expression of pre-S1, pre-S2, S and X peptides in relation to viral replication in livers with chronic hepatitis B. Liver. 1990 Dec;10(6):355–364. doi: 10.1111/j.1600-0676.1990.tb00481.x. [DOI] [PubMed] [Google Scholar]
  29. Takaguchi K., Yamada G., Tsuji T. Immunohistochemical study of pre-S(2) antigen in liver and serum of patients with chronic hepatitis B. Gastroenterol Jpn. 1990 Jun;25(3):343–349. doi: 10.1007/BF02779449. [DOI] [PubMed] [Google Scholar]
  30. Takai E., Machida A., Ohnuma H., Miyamoto H., Tanaka T., Baba K., Tsuda F., Usuda S., Nakamura T., Miyakawa Y. A solid-phase enzyme immunoassay for the determination of IgM and IgG antibodies against translation products of pre-S1 and pre-S2 regions of hepatitis B virus. J Immunol Methods. 1986 Dec 4;95(1):23–30. doi: 10.1016/0022-1759(86)90313-3. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Thung S. N., Gerber M. A., Kasambalides E. J., Gilja B. K., Keh W., Gerlich W. H. Demonstration of pre-S polypeptides of hepatitis B virus in infected livers. Hepatology. 1986 Nov-Dec;6(6):1315–1318. doi: 10.1002/hep.1840060615. [DOI] [PubMed] [Google Scholar]
  33. 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]

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