Skip to main content
NCBI home page
The EMBO Journal logoLink to The EMBO Journal
. 1988 Mar;7(3):819–824. doi: 10.1002/j.1460-2075.1988.tb02880.x

A model for the hepatitis B virus core protein: prediction of antigenic sites and relationship to RNA virus capsid proteins.

P Argos 1, S D Fuller 1
PMCID: PMC454397  PMID: 2456212

Abstract

The sequences of the core proteins from several serotypes of human hepatitis B virus and related mammalian and avian hepadnaviruses are aligned with the vp3 capsid protein of mengo virus, a picornavirus. The homology indicates an eight-stranded antiparallel beta-barrel fold for the hepatitis protein, as observed in the tertiary structure of the picornavirus protein. The locations of known antigenic sites and other modifications are consistent with this structure for the core protein. The predicted folding suggests additional exposed antigenic sites and supports an evolutionary relationship between this family of enveloped DNA viruses and enveloped and non-enveloped RNA viruses.

Full text

PDF
819

Selected References

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

  1. Albin C., Robinson W. S. Protein kinase activity in hepatitis B virus. J Virol. 1980 Apr;34(1):297–302. doi: 10.1128/jvi.34.1.297-302.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Argos P. A sensitive procedure to compare amino acid sequences. J Mol Biol. 1987 Jan 20;193(2):385–396. doi: 10.1016/0022-2836(87)90226-9. [DOI] [PubMed] [Google Scholar]
  3. Bichko V., Pushko P., Dreilina D., Pumpen P., Gren E. Subtype ayw variant of hepatitis B virus. DNA primary structure analysis. FEBS Lett. 1985 Jun 3;185(1):208–212. doi: 10.1016/0014-5793(85)80771-7. [DOI] [PubMed] [Google Scholar]
  4. Budkowska A., Kalinowska B., Nowosławski A. Identification of two HBeAg subspecificities revealed by chemical treatment and enzymatic digestion of liver-derived HBcAg. J Immunol. 1979 Sep;123(3):1415–1416. [PubMed] [Google Scholar]
  5. Delpeyroux F., Chenciner N., Lim A., Malpièce Y., Blondel B., Crainic R., van der Werf S., Streeck R. E. A poliovirus neutralization epitope expressed on hybrid hepatitis B surface antigen particles. Science. 1986 Jul 25;233(4762):472–475. doi: 10.1126/science.2425433. [DOI] [PubMed] [Google Scholar]
  6. Eddleston A. L., Williams R. Inadequate antibody response to hBAg or suppressor T-cell defect in development of active chronic hepatitis. Lancet. 1974 Dec 28;2(7896):1543–1545. doi: 10.1016/s0140-6736(74)90287-6. [DOI] [PubMed] [Google Scholar]
  7. Feitelson M. A., Marion P. L., Robinson W. S. Antigenic and structural relationships of the surface antigens of hepatitis B virus, ground squirrel hepatitis virus, and woodchuck hepatitis virus. J Virol. 1981 Aug;39(2):447–454. doi: 10.1128/jvi.39.2.447-454.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Feitelson M. A., Marion P. L., Robinson W. S. Core particles of hepatitis B virus and ground squirrel hepatitis virus. I. Relationship between hepatitis B core antigen- and ground squirrel hepatitis core antigen-associated polypeptides by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and tryptic peptide mapping. J Virol. 1982 Aug;43(2):687–696. doi: 10.1128/jvi.43.2.687-696.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Feitelson M. A., Marion P. L., Robinson W. S. Core particles of hepatitis B virus and ground squirrel hepatitis virus. II. Characterization of the protein kinase reaction associated with ground squirrel hepatitis virus and hepatitis B virus. J Virol. 1982 Aug;43(2):741–748. doi: 10.1128/jvi.43.2.741-748.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fujiyama A., Miyanohara A., Nozaki C., Yoneyama T., Ohtomo N., Matsubara K. Cloning and structural analyses of hepatitis B virus DNAs, subtype adr. Nucleic Acids Res. 1983 Jul 11;11(13):4601–4610. doi: 10.1093/nar/11.13.4601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fuller S. D., Argos P. Is Sindbis a simple picornavirus with an envelope? EMBO J. 1987 Apr;6(4):1099–1105. doi: 10.1002/j.1460-2075.1987.tb04864.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Galibert F., Chen T. N., Mandart E. Nucleotide sequence of a cloned woodchuck hepatitis virus genome: comparison with the hepatitis B virus sequence. J Virol. 1982 Jan;41(1):51–65. doi: 10.1128/jvi.41.1.51-65.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Gerety R. J., Tabor E., Purcell R. H., Tyeryar F. J. Summary of an international workshop on hepatitis B vaccines. J Infect Dis. 1979 Oct;140(4):642–648. doi: 10.1093/infdis/140.4.642. [DOI] [PubMed] [Google Scholar]
  16. Hogle J. M., Chow M., Filman D. J. Three-dimensional structure of poliovirus at 2.9 A resolution. Science. 1985 Sep 27;229(4720):1358–1365. doi: 10.1126/science.2994218. [DOI] [PubMed] [Google Scholar]
  17. Jones D. D. Amino acid properties and side-chain orientation in proteins: a cross correlation appraoch. J Theor Biol. 1975 Mar;50(1):167–183. doi: 10.1016/0022-5193(75)90031-4. [DOI] [PubMed] [Google Scholar]
  18. Kamer G., Argos P. Primary structural comparison of RNA-dependent polymerases from plant, animal and bacterial viruses. Nucleic Acids Res. 1984 Sep 25;12(18):7269–7282. doi: 10.1093/nar/12.18.7269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Luo M., Vriend G., Kamer G., Minor I., Arnold E., Rossmann M. G., Boege U., Scraba D. G., Duke G. M., Palmenberg A. C. The atomic structure of Mengo virus at 3.0 A resolution. Science. 1987 Jan 9;235(4785):182–191. doi: 10.1126/science.3026048. [DOI] [PubMed] [Google Scholar]
  20. MacKay P., Lees J., Murray K. The conversion of hepatitis B core antigen synthesized in E coli into e antigen. J Med Virol. 1981;8(4):237–243. doi: 10.1002/jmv.1890080404. [DOI] [PubMed] [Google Scholar]
  21. Manavalan P., Ponnuswamy P. K. Hydrophobic character of amino acid residues in globular proteins. Nature. 1978 Oct 19;275(5681):673–674. doi: 10.1038/275673a0. [DOI] [PubMed] [Google Scholar]
  22. Mandart E., Kay A., Galibert F. Nucleotide sequence of a cloned duck hepatitis B virus genome: comparison with woodchuck and human hepatitis B virus sequences. J Virol. 1984 Mar;49(3):782–792. doi: 10.1128/jvi.49.3.782-792.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Marion P. L., Robinson W. S. Hepadna viruses: hepatitis B and related viruses. Curr Top Microbiol Immunol. 1983;105:99–121. doi: 10.1007/978-3-642-69159-1_2. [DOI] [PubMed] [Google Scholar]
  24. Mason W. S., Seal G., Summers J. Virus of Pekin ducks with structural and biological relatedness to human hepatitis B virus. J Virol. 1980 Dec;36(3):829–836. doi: 10.1128/jvi.36.3.829-836.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. McLachlan A. D. Tests for comparing related amino-acid sequences. Cytochrome c and cytochrome c 551 . J Mol Biol. 1971 Oct 28;61(2):409–424. doi: 10.1016/0022-2836(71)90390-1. [DOI] [PubMed] [Google Scholar]
  26. Milich D. R., Louie R. E., Chisari F. V. Genetic regulation of the immune response to hepatitis B surface antigen (HBsAg). V. T cell proliferative response and cellular interactions. J Immunol. 1985 Jun;134(6):4194–4202. [PubMed] [Google Scholar]
  27. Milich D. R., McLachlan A., Moriarty A., Thornton G. B. Immune response to hepatitis B virus core antigen (HBcAg): localization of T cell recognition sites within HBcAg/HBeAg. J Immunol. 1987 Aug 15;139(4):1223–1231. [PubMed] [Google Scholar]
  28. Milich D. R., McLachlan A. The nucleocapsid of hepatitis B virus is both a T-cell-independent and a T-cell-dependent antigen. Science. 1986 Dec 12;234(4782):1398–1401. doi: 10.1126/science.3491425. [DOI] [PubMed] [Google Scholar]
  29. Milich D. R., McLachlan A., Thornton G. B., Hughes J. L. Antibody production to the nucleocapsid and envelope of the hepatitis B virus primed by a single synthetic T cell site. Nature. 1987 Oct 8;329(6139):547–549. doi: 10.1038/329547a0. [DOI] [PubMed] [Google Scholar]
  30. Miller R. H., Robinson W. S. Common evolutionary origin of hepatitis B virus and retroviruses. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2531–2535. doi: 10.1073/pnas.83.8.2531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Murray K., Bruce S. A., Hinnen A., Wingfield P., van Erd P. M., de Reus A., Schellekens H. Hepatitis B virus antigens made in microbial cells immunise against viral infection. EMBO J. 1984 Mar;3(3):645–650. doi: 10.1002/j.1460-2075.1984.tb01861.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ohori H., Shimizu N., Yamada E., Onodera S., Ishida N. Immunological and morphological properties of HBeAg subtypes (HBeAg/1 and HBeAg/2) in hepatitis B virus core particles. J Gen Virol. 1984 Feb;65(Pt 2):405–414. doi: 10.1099/0022-1317-65-2-405. [DOI] [PubMed] [Google Scholar]
  34. Ohori H., Yamaki M., Onodera S., Yamada E., Ishida N. Antigenic conversion from HBcAg to HBeAg by degradation of hepatitis B core particles. Intervirology. 1980;13(2):74–82. doi: 10.1159/000149110. [DOI] [PubMed] [Google Scholar]
  35. Ono Y., Onda H., Sasada R., Igarashi K., Sugino Y., Nishioka K. The complete nucleotide sequences of the cloned hepatitis B virus DNA; subtype adr and adw. Nucleic Acids Res. 1983 Mar 25;11(6):1747–1757. doi: 10.1093/nar/11.6.1747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Onodera S., Ohori H., Yamaki M., Ishida N. Electron microscopy of human hepatitis B virus cores by negative staining-carbon film technique. J Med Virol. 1982;10(2):147–155. doi: 10.1002/jmv.1890100209. [DOI] [PubMed] [Google Scholar]
  37. Palau J., Argos P., Puigdomenech P. Protein secondary structure. Studies on the limits of prediction accuracy. Int J Pept Protein Res. 1982 Apr;19(4):394–401. [PubMed] [Google Scholar]
  38. Pasek M., Goto T., Gilbert W., Zink B., Schaller H., MacKay P., Leadbetter G., Murray K. Hepatitis B virus genes and their expression in E. coli. Nature. 1979 Dec 6;282(5739):575–579. doi: 10.1038/282575a0. [DOI] [PubMed] [Google Scholar]
  39. Rossmann M. G., Arnold E., Erickson J. W., Frankenberger E. A., Griffith J. P., Hecht H. J., Johnson J. E., Kamer G., Luo M., Mosser A. G. Structure of a human common cold virus and functional relationship to other picornaviruses. Nature. 1985 Sep 12;317(6033):145–153. doi: 10.1038/317145a0. [DOI] [PubMed] [Google Scholar]
  40. Seeger C., Ganem D., Varmus H. E. Nucleotide sequence of an infectious molecularly cloned genome of ground squirrel hepatitis virus. J Virol. 1984 Aug;51(2):367–375. doi: 10.1128/jvi.51.2.367-375.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Smith T. F., Waterman M. S. Identification of common molecular subsequences. J Mol Biol. 1981 Mar 25;147(1):195–197. doi: 10.1016/0022-2836(81)90087-5. [DOI] [PubMed] [Google Scholar]
  42. Tabor E., Gerety R. J. Possible role of immune responses to hepatitis B core antigen in protection against hepatitis B infections. Lancet. 1984 Jan 21;1(8369):172–172. doi: 10.1016/s0140-6736(84)90114-4. [DOI] [PubMed] [Google Scholar]
  43. Takahashi K., Akahane Y., Gotanda T., Mishiro T., Imai M., Miyakawa Y., Mayumi M. Demonstration of hepatitis B e antigen in the core of Dane particles. J Immunol. 1979 Jan;122(1):275–279. [PubMed] [Google Scholar]
  44. Takahashi K., Machida A., Funatsu G., Nomura M., Usuda S., Aoyagi S., Tachibana K., Miyamoto H., Imai M., Nakamura T. Immunochemical structure of hepatitis B e antigen in the serum. J Immunol. 1983 Jun;130(6):2903–2907. [PubMed] [Google Scholar]
  45. Tiollais P., Charnay P., Vyas G. N. Biology of hepatitis B virus. Science. 1981 Jul 24;213(4506):406–411. doi: 10.1126/science.6264599. [DOI] [PubMed] [Google Scholar]
  46. 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]
  47. Toh H., Hayashida H., Miyata T. Sequence homology between retroviral reverse transcriptase and putative polymerases of hepatitis B virus and cauliflower mosaic virus. 1983 Oct 27-Nov 2Nature. 305(5937):827–829. doi: 10.1038/305827a0. [DOI] [PubMed] [Google Scholar]
  48. Williams A., Le Bouvier G. Heterogeneity and thermolability of 'e'. Bibl Haematol. 1976;42:71–75. doi: 10.1159/000398996. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES