Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1989 May;63(5):1981–1988. doi: 10.1128/jvi.63.5.1981-1988.1989

Human liver plasma membranes contain receptors for the hepatitis B virus pre-S1 region and, via polymerized human serum albumin, for the pre-S2 region.

P Pontisso 1, M A Petit 1, M J Bankowski 1, M E Peeples 1
PMCID: PMC250612  PMID: 2649690

Abstract

Hepatitis B virus particles contain three related viral envelope proteins, the small, middle, and large S (surface) proteins. All three proteins contain the small S amino acid sequence at their carboxyl terminus. It is not clear which of these S proteins functions as the viral attachment protein, binding to a target cell receptor and initiating infection. In this report, recombinant hepatitis B surface antigen (rHBsAg) particles, which contain only virus envelope proteins, were radioactively labeled, and their attachment to human liver membranes was examined. Only the rHBsAg particles containing the large S protein were capable of directly attaching to liver plasma membranes. The attachment was saturable and could be prevented by competition with unlabeled particles or by a monoclonal antibody specific for the large S protein. In the presence of polymerized human serum albumin, both large and middle S protein-containing rHBsAg particles were capable of attaching to the liver plasma membranes. Small S protein-containing rHBsAg particles were not able to attach even in the presence of polymerized human serum albumin. These results indicate that the large S protein may be the viral attachment protein for hepatocytes, binding directly to liver plasma membranes by its unique amino-terminal (pre-S1) sequence. These results also indicate that polymerized human serum albumin or a similar molecule could act as an intermediate receptor, attaching to liver plasma membranes and to the amino acid sequence (pre-S2) shared by the middle and large S proteins but not contained in the small S protein.

Full text

PDF
1981

Images in this article

1983Image
on p.1983

Selected References

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

  1. Alberti A., Diana S., Sculard G. H., Eddleston A. L., Williams R. Detection of a new antibody system reacting with Dane particles in hepatitis B virus infection. Br Med J. 1978 Oct 14;2(6144):1056–1058. doi: 10.1136/bmj.2.6144.1056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alberti A., Pontisso P., Schiavon E., Realdi G. An antibody which precipitates Dane particles in acute hepatitis type B: relation to receptor sites which bind polymerized human serum albumin on virus particles. Hepatology. 1984 Mar-Apr;4(2):220–226. doi: 10.1002/hep.1840040209. [DOI] [PubMed] [Google Scholar]
  3. Blum H. E., Stowring L., Figus A., Montgomery C. K., Haase A. T., Vyas G. N. Detection of hepatitis B virus DNA in hepatocytes, bile duct epithelium, and vascular elements by in situ hybridization. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6685–6688. doi: 10.1073/pnas.80.21.6685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Budkowska A., Dubreuil P., Capel F., Pillot J. Hepatitis B virus pre-S gene-encoded antigenic specificity and anti-pre-S antibody: relationship between anti-pre-S response and recovery. Hepatology. 1986 May-Jun;6(3):360–368. doi: 10.1002/hep.1840060305. [DOI] [PubMed] [Google Scholar]
  5. Budkowska A., Dubreuil P., Riottot M. M., Briantais M. J., Pillot J. A monoclonal antibody enzyme immunoassay for the detection of epitopes encoded by the pre-S2 region of the hepatitis B virus genome. J Immunol Methods. 1987 Feb 26;97(1):77–85. doi: 10.1016/0022-1759(87)90108-6. [DOI] [PubMed] [Google Scholar]
  6. Budkowska A., Riottot M. M., Dubreuil P., Lazizi Y., Brechot C., Sobczak E., Petit M. A., Pillot J. Monoclonal antibody recognizing pre-S(2) epitope of hepatitis B virus: characterization of pre-S(2) epitope and anti-pre-S(2) antibody. J Med Virol. 1986 Oct;20(2):111–125. doi: 10.1002/jmv.1890200204. [DOI] [PubMed] [Google Scholar]
  7. Dejean A., Lugassy C., Zafrani S., Tiollais P., Brechot C. Detection of hepatitis B virus DNA in pancreas, kidney and skin of two human carriers of the virus. J Gen Virol. 1984 Mar;65(Pt 3):651–655. doi: 10.1099/0022-1317-65-3-651. [DOI] [PubMed] [Google Scholar]
  8. Elfassi E., Romet-Lemonne J. L., Essex M., Frances-McLane M., Haseltine W. A. Evidence of extrachromosomal forms of hepatitis B viral DNA in a bone marrow culture obtained from a patient recently infected with hepatitis B virus. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3526–3528. doi: 10.1073/pnas.81.11.3526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gu J. R., Chen Y. C., Jiang H. Q., Zhang Y. L., Wu S. M., Jiang W. L., Jian J. State of hepatitis B virus DNA in leucocytes of hepatitis B patients. J Med Virol. 1985 Sep;17(1):73–81. doi: 10.1002/jmv.1890170111. [DOI] [PubMed] [Google Scholar]
  10. Halpern M. S., Egan J., McMahon S. B., Ewert D. L. Duck hepatitis B virus is tropic for exocrine cells of the pancreas. Virology. 1985 Oct 15;146(1):157–161. doi: 10.1016/0042-6822(85)90064-9. [DOI] [PubMed] [Google Scholar]
  11. Halpern M. S., England J. M., Deery D. T., Petcu D. J., Mason W. S., Molnar-Kimber K. L. Viral nucleic acid synthesis and antigen accumulation in pancreas and kidney of Pekin ducks infected with duck hepatitis B virus. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4865–4869. doi: 10.1073/pnas.80.15.4865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hansson B. G., Purcell R. H. Sites that bind polymerized albumin on hepatitis B surface antigen particles: detection by radioimmunoassay. Infect Immun. 1979 Oct;26(1):125–130. doi: 10.1128/iai.26.1.125-130.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Hubbard A. L., Wall D. A., Ma A. Isolation of rat hepatocyte plasma membranes. I. Presence of the three major domains. J Cell Biol. 1983 Jan;96(1):217–229. doi: 10.1083/jcb.96.1.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Imai M., Yanase Y., Nojiri T., Miyakawa Y., Mayumi M. A receptor for polymerized human and chimpanzee albumins on hepatitis B virus particles co-occurring with HBeAg. Gastroenterology. 1979 Feb;76(2):242–247. [PubMed] [Google Scholar]
  16. Iorio R. M., Bratt M. A. Monoclonal antibodies to newcastle disease virus: delineation of four epitopes on the HN glycoprotein. J Virol. 1983 Nov;48(2):440–450. doi: 10.1128/jvi.48.2.440-450.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Itoh Y., Takai E., Ohnuma H., Kitajima K., Tsuda F., Machida A., Mishiro S., Nakamura T., Miyakawa Y., Mayumi M. A synthetic peptide vaccine involving the product of the pre-S(2) region of hepatitis B virus DNA: protective efficacy in chimpanzees. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9174–9178. doi: 10.1073/pnas.83.23.9174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Kniskern P. J., Hagopian A., Burke P., Dunn N., Emini E. A., Miller W. J., Yamazaki S., Ellis R. W. A candidate vaccine for hepatitis B containing the complete viral surface protein. Hepatology. 1988 Jan-Feb;8(1):82–87. doi: 10.1002/hep.1840080117. [DOI] [PubMed] [Google Scholar]
  20. Komai K., Kaplan M., Peeples M. E. The Vero cell receptor for the hepatitis B virus small S protein is a sialoglycoprotein. Virology. 1988 Apr;163(2):629–634. doi: 10.1016/0042-6822(88)90306-6. [DOI] [PubMed] [Google Scholar]
  21. Korba B. E., Wells F., Tennant B. C., Cote P. J., Gerin J. L. Lymphoid cells in the spleens of woodchuck hepatitis virus-infected woodchucks are a site of active viral replication. J Virol. 1987 May;61(5):1318–1324. doi: 10.1128/jvi.61.5.1318-1324.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Korba B. E., Wells F., Tennant B. C., Yoakum G. H., Purcell R. H., Gerin J. L. Hepadnavirus infection of peripheral blood lymphocytes in vivo: woodchuck and chimpanzee models of viral hepatitis. J Virol. 1986 Apr;58(1):1–8. doi: 10.1128/jvi.58.1.1-8.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lenkei R., Onica D., Ghetie V. Receptors for polymerized albumin on liver cells. Experientia. 1977 Aug 15;33(8):1046–1047. doi: 10.1007/BF01945961. [DOI] [PubMed] [Google Scholar]
  24. Lieberman H. M., Tung W. W., Shafritz D. A. Splenic replication of hepatitis B virus in the chimpanzee chronic carrier. J Med Virol. 1987 Apr;21(4):347–359. doi: 10.1002/jmv.1890210407. [DOI] [PubMed] [Google Scholar]
  25. Machida A., Kishimoto S., Ohnuma H., Baba K., Ito Y., Miyamoto H., Funatsu G., Oda K., Usuda S., Togami S. A polypeptide containing 55 amino acid residues coded by the pre-S region of hepatitis B virus deoxyribonucleic acid bears the receptor for polymerized human as well as chimpanzee albumins. Gastroenterology. 1984 May;86(5 Pt 1):910–918. [PubMed] [Google Scholar]
  26. Machida A., Kishimoto S., Ohnuma H., Miyamoto H., Baba K., Oda K., Nakamura T., Miyakawa Y., Mayumi M. A hepatitis B surface antigen polypeptide (P31) with the receptor for polymerized human as well as chimpanzee albumins. Gastroenterology. 1983 Aug;85(2):268–274. [PubMed] [Google Scholar]
  27. 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]
  28. Neurath A. R., Kent S. B., Parker K., Prince A. M., Strick N., Brotman B., Sproul P. Antibodies to a synthetic peptide from the preS 120-145 region of the hepatitis B virus envelope are virus neutralizing. Vaccine. 1986 Mar;4(1):35–37. doi: 10.1016/s0264-410x(86)80001-9. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Okamoto H., Usuda S., Imai M., Tachibana K., Tanaka E., Kumakura T., Itabashi M., Takai E., Tsuda F., Nakamura T. Antibody to the receptor for polymerized human serum albumin in acute and persistent infection with hepatitis B virus. Hepatology. 1986 May-Jun;6(3):354–359. doi: 10.1002/hep.1840060304. [DOI] [PubMed] [Google Scholar]
  31. Olmsted R. A., Elango N., Prince G. A., Murphy B. R., Johnson P. R., Moss B., Chanock R. M., Collins P. L. Expression of the F glycoprotein of respiratory syncytial virus by a recombinant vaccinia virus: comparison of the individual contributions of the F and G glycoproteins to host immunity. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7462–7466. doi: 10.1073/pnas.83.19.7462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Peeples M. E., Komai K., Radek R., Bankowski M. J. A cultured cell receptor for the small S protein of hepatitis B virus. Virology. 1987 Sep;160(1):135–142. doi: 10.1016/0042-6822(87)90053-5. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. Petit M. A., Capel F., Riottot M. M., Dauguet C., Pillot J. Antigenic mapping of the surface proteins of infectious hepatitis B virus particles. J Gen Virol. 1987 Nov;68(Pt 11):2759–2767. doi: 10.1099/0022-1317-68-11-2759. [DOI] [PubMed] [Google Scholar]
  37. Pontisso P., Alberti A., Schiavon E., Tremolada F., Bortolotti F., Realdi G. Receptors for polymerized human serum albumin on hepatitis B virus particles detected by radioimmunoassay: changes in receptor activity in serum during acute and chronic infection. J Virol Methods. 1983 Mar;6(3):151–159. doi: 10.1016/0166-0934(83)90027-7. [DOI] [PubMed] [Google Scholar]
  38. Pontisso P., Locasciulli A., Schiavon E., Cattoretti G., Schirò R., Stenico D., Alberti A. Detection of hepatitis B virus DNA sequences in bone marrow of children with leukemia. Cancer. 1987 Jan 15;59(2):292–296. doi: 10.1002/1097-0142(19870115)59:2<292::aid-cncr2820590220>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  39. Pontisso P., Poon M. C., Tiollais P., Brechot C. Detection of hepatitis B virus DNA in mononuclear blood cells. Br Med J (Clin Res Ed) 1984 May 26;288(6430):1563–1566. doi: 10.1136/bmj.288.6430.1563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Pontisso P., Schiavon E., Fraiese A., Pornaro E., Realdi G., Alberti A. Antibody to the hepatitis B virus receptor for polymerized albumin in acute infection and in hepatitis B vaccine recipients. J Hepatol. 1986;3(3):393–398. doi: 10.1016/s0168-8278(86)80494-9. [DOI] [PubMed] [Google Scholar]
  41. Pugh J. C., Sninsky J. J., Summers J. W., Schaeffer E. Characterization of a pre-S polypeptide on the surfaces of infectious avian hepadnavirus particles. J Virol. 1987 May;61(5):1384–1390. doi: 10.1128/jvi.61.5.1384-1390.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Romet-Lemonne J. L., McLane M. F., Elfassi E., Haseltine W. A., Azocar J., Essex M. Hepatitis B virus infection in cultured human lymphoblastoid cells. Science. 1983 Aug 12;221(4611):667–669. doi: 10.1126/science.6867736. [DOI] [PubMed] [Google Scholar]
  43. 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]
  44. Siddiqui A. Hepatitis B virus DNA in Kaposi sarcoma. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4861–4864. doi: 10.1073/pnas.80.15.4861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Tagawa M., Omata M., Yokosuka O., Uchiumi K., Imazeki F., Okuda K. Early events in duck hepatitis B virus infection. Sequential appearance of viral deoxyribonucleic acid in the liver, pancreas, kidney, and spleen. Gastroenterology. 1985 Dec;89(6):1224–1229. [PubMed] [Google Scholar]
  46. Tagawa M., Robinson W. S., Marion P. L. Duck hepatitis B virus replicates in the yolk sac of developing embryos. J Virol. 1987 Jul;61(7):2273–2279. doi: 10.1128/jvi.61.7.2273-2279.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. 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]
  48. 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]
  49. Trevisan A., Gudat F., Guggenheim R., Krey G., Dürmüller U., Lüond G., Düggelin M., Landmann J., Tondelli P., Bianchi L. Demonstration of albumin receptors on isolated human hepatocytes by light and scanning electron microscopy. Hepatology. 1982 Nov-Dec;2(6):832–835. doi: 10.1002/hep.1840020616. [DOI] [PubMed] [Google Scholar]
  50. Wiley D. C., Wilson I. A., Skehel J. J. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature. 1981 Jan 29;289(5796):373–378. doi: 10.1038/289373a0. [DOI] [PubMed] [Google Scholar]
  51. Wong D. T., Nath N., Sninsky J. J. Identification of hepatitis B virus polypeptides encoded by the entire pre-s open reading frame. J Virol. 1985 Jul;55(1):223–231. doi: 10.1128/jvi.55.1.223-231.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Wright T. L., Lysenko N., Ockner R. K., Weisiger R. A. Interaction of natural and synthetic albumin polymers with hepatocytes. Hepatology. 1987 Mar-Apr;7(2):294–301. doi: 10.1002/hep.1840070214. [DOI] [PubMed] [Google Scholar]
  53. Yoffe B., Noonan C. A., Melnick J. L., Hollinger F. B. Hepatitis B virus DNA in mononuclear cells and analysis of cell subsets for the presence of replicative intermediates of viral DNA. J Infect Dis. 1986 Mar;153(3):471–477. doi: 10.1093/infdis/153.3.471. [DOI] [PubMed] [Google Scholar]
  54. Yu M. W., Finlayson J. S., Shih J. W. Interaction between various polymerized human albumins and hepatitis B surface antigen. J Virol. 1985 Sep;55(3):736–743. doi: 10.1128/jvi.55.3.736-743.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES