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Hepatitis B virus genome is organized into nucleosomes in the nucleus of the infected cell

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Abstract

Hepatitis B virus (HBV) nucleoprotein complexes were isolated from nuclei of the human hepatoblastoma cell line HepG2.2.15. Under conditions of physiological ionic strength, the complexes sedimented at a rate corresponding to about 82 S. They contained viral DNA, histone, and nonhistone proteins. For DNA a circular, covalently closed structure was shown both by CsCl gradient centrifugation and electron microscopy. Spread preparations revealed the typical “beads-on-a-string” appearance of nucleosomally organized DNA. The average number of nucleosomes was 18, resulting in a biochemical repeat unit of HBV chromatin of approximately 180 base pairs of DNA. This value was confirmed by experiments analyzing the structure of the HBV chromatin by the use of micrococcal nuclease. Electron microscopy demonstrated that exposure to high ionic strength conditions resulted in removal of nucleosomes from the complexes, but also revealed proteinaceous structures remaining bound to viral DNA molecules. The nature of these residual proteins is discussed. Since native nucleoprotein complexes could be precipitated with HBV-core antibodies, core protein appeared to be one of the nonhistone proteins.

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References

  1. Oudet P., Germond J.E., Bellard M., Spadafora C., and Chambon P., Phil Trans R Soc Lond B283 241–258, 1978.

    Google Scholar 

  2. Simpson R.T., Prog Nucleic Acids Res Mol Biol40 143–184, 1991.

    Google Scholar 

  3. Felsenfield G., Nature355 219–224, 1992.

    Google Scholar 

  4. Green M.H., Miller H.I., and Hendler S., Proc Natl Acad Sci USA68 1032–1036, 1971.

    Google Scholar 

  5. White M. and Eason R., J Virol8 363–371, 1971.

    Google Scholar 

  6. Cremisi C., Pignatti P.F., Croissant O., and Yaniv M., J Virol17 204–211, 1976.

    Google Scholar 

  7. Favre M., Breitburd F., Croissant O., and Orth G., J Virol21 1205–1209, 1977.

    Google Scholar 

  8. Rösl F., Waldeck W., Zentgraf H., and Sauer G., J Virol58 500–507, 1986.

    Google Scholar 

  9. Germond J.E., Hirt B., Oudet P., Gross-Bellard M., and Chambon P., Proc Natl Acad Sci USA72 1843–1847, 1975.

    Google Scholar 

  10. Keller W., Müller U., Eicken I., Wendel I., and Zentgraf H., Cold Spring Harbor Symp Quant Biol42 227–244, 1978.

    Google Scholar 

  11. Müller U., Zentgraf H., Eicken I., and Keller W., Science201 406–415, 1978.

    Google Scholar 

  12. Mirza M.A., and Weber J., Biochim Biophys Acta696 72–86, 1982.

    Google Scholar 

  13. Corden J., Engelking H.M., and Pearson G.D., Proc Natl Acad Sci USA73 401–404, 1976.

    Google Scholar 

  14. Kedinger C., Brison O., Perrin F., and Wilhelm J., J Virol26 364–379, 1978.

    Google Scholar 

  15. Leinbach S.S. and Summers W.C., J Gen Virol51 45–59, 1980.

    Google Scholar 

  16. Müller U., Schröder C.H., Zentgraf H., and Franke W.W., Eur J Cell Biol23 197–203, 1980.

    Google Scholar 

  17. Pignatti P.F. and Cassi E., J Virol36 816–828, 1980.

    Google Scholar 

  18. Ganem D., Rev Infect Dis4 1026–1047, 1982.

    Google Scholar 

  19. Szmuness W., Prog Med Virol24 40–69, 1978.

    Google Scholar 

  20. Beasley R.P., Cancer61 1942–1956, 1988.

    Google Scholar 

  21. Ganem D. and Varmus H.E., Ann Rev Biochem56 651–693, 1987.

    Google Scholar 

  22. Bosch V., Bartenschlager R., Radziwill G., and Schaller H., Virology166 475–485, 1988.

    Google Scholar 

  23. Tiollais P., Pourcel C., and DeJean A., Nature317 489–495, 1985.

    Google Scholar 

  24. Gerlich W.H. and Robinson W.S., Cell21 801–809, 1980.

    Google Scholar 

  25. Lien J.-M., Aldrich C.E., and Mason W.S., J Virol57 229–236, 1985.

    Google Scholar 

  26. Seeger C. and Maragos J., J Virol63 1907–1925, 1989.

    Google Scholar 

  27. Delius H., Gough M.N., Cameron C.H., and Murray K., J Virol47 337–343, 1983.

    Google Scholar 

  28. Will H., Reiser W., Weimer T., Pfaff E., Büscher M., Spregler R., Cattaneo R., and Schaller H., J Virol61 904–911, 1987.

    Google Scholar 

  29. Ganem D. and Varmus H.E., Ann Rev Biochem56 651–693, 1987.

    Google Scholar 

  30. Cattaneo R., Will H., and Schaller H., EMBO J3 2191–2196, 1984.

    Google Scholar 

  31. Ou J.-H., Bao H., Shili C., and Tahara S.M., J Virol64 4578–4581, 1990.

    Google Scholar 

  32. Farza H., Hadchouel M., Scotto J., Tiollais P., Babinet C., and Pourcel C., J Virol62 4144–4152, 1988.

    Google Scholar 

  33. Suzuki T., Masui N., Kajino K., Saito I., and Miyamura T., Proc Natl Acad Sci USA86 8422–8426, 1989.

    Google Scholar 

  34. Saito I., Oya Y., and Shimojo H., J Virol58 554–560, 1986.

    Google Scholar 

  35. Siddiqui A., Jameel S., and Mapoles J., Proc Natl Acad Sci USA84 2513–2517, 1987.

    Google Scholar 

  36. Miller R.H. and Robinson W.S., Virology137 390–399, 1984.

    Google Scholar 

  37. Sells M.A., Chen M.-L., and Acs G., Proc Natl Acad Sci USA84 1005–1009, 1987.

    Google Scholar 

  38. Sells M.A., Zelent A.Z., Shvartsman M., and Acs, G., J Virol62 2836–2844, 1988.

    Google Scholar 

  39. Gerber M.A., Sells M.A., Chen M.-L., Thung S.N., Tabibzadeh S.S., Hood A., and Acs G., Lab Invest59 173–180, 1988.

    Google Scholar 

  40. Knowles B., Howe C.C., and Aden D.P., Science209 497–499, 1980.

    Google Scholar 

  41. Aden D.P., Fogel A., Plotkin S., Damjanov I., and Knowles B., Nature282 615–616, 1979.

    Google Scholar 

  42. Su R.T. and DePamphilis M.L., J Virol28 53–65, 1978.

    Google Scholar 

  43. Waldeck W., Spaere U., Mastromei G., Eliasson R., and Reichard P., J Mol Biol135 675–689, 1979.

    Google Scholar 

  44. Sinsheimer R.L., J Mol Biol1 43, 1959.

    Google Scholar 

  45. Marvin D.A. and Hoffmann-Berling G., Nature197 517–518, 1963.

    Google Scholar 

  46. Fraenkel-Conrat H.,The Viruses, Catalogue, Characterisation, and Classification. Plenum Press, New York, 1971, p. 209.

    Google Scholar 

  47. Horwich A.L., Furtak K., Pugh J., and Summers J., J Virol64 642–650, 1990.

    Google Scholar 

  48. Laemmli U.K., Nature227 680–685, 1970.

    Google Scholar 

  49. Thomas J.O. and Kornberg R.D., J Mol Biol149 709–733, 1975.

    Google Scholar 

  50. Switzer R.C., Merril C.R., and Shifrin S., Anal Biochem98 231–237, 1979.

    Google Scholar 

  51. Khyse-Andersen J., J Biochem Biophys Methods10 203–209, 1984.

    Google Scholar 

  52. McDonell M.W., Simon M.N., and Studier F.W., J Mol Biol110 119–146, 1977.

    Google Scholar 

  53. Southern E.M., J Mol Biol98 503–517, 1975.

    Google Scholar 

  54. Loncarevic I.F., Schranz P., Zentgraf H., Liang X.-H., Herrmann G., Tang Z.-Y., and Schroeder C.H., Virology174 158–168, 1990.

    Google Scholar 

  55. Lawson G.M., Tsai M.J., and O'Mally B.W., Biochemistry19 4403–4411, 1980.

    Google Scholar 

  56. Miller O.L., and Beatty B.R., Science164 955–957, 1969.

    Google Scholar 

  57. Bock C.-T. and Zentgraf H., Chromosoma102 249–252, 1993.

    Google Scholar 

  58. Vollenweider H.J., Sogo J.M., and Koller T., Proc Natl Acad Sci USA72 83–91, 1975.

    Google Scholar 

  59. Scheer U. and Zentgraf H., Chromosoma69 243–254, 1978.

    Google Scholar 

  60. Tuttleman J., Pourcel C., and Summers J., Cell47 451–460, 1986.

    Google Scholar 

  61. Nassal M., J Virol66 4107–4116, 1992.

    Google Scholar 

  62. Studier F.W., J Mol Biol11 373–390, 1965.

    Google Scholar 

  63. Simon R.H. and Felsenfeld G., Nucleic Acids Res6 689–696, 1979.

    Google Scholar 

  64. Morris R., Cell9 627–632, 1976.

    Google Scholar 

  65. Noll M. and Kornberg R.D., J Mol Biol109 393–396, 1977.

    Google Scholar 

  66. Zentgraf H., Trendelenburg M.F., Spring H., Scheer U., Franke W.W., Müller U., Drury K.C., and Rungger D., Exp Cell Res122 363–375, 1979.

    Google Scholar 

  67. Hatton T., Zhou S., and Standring D.N., J Virol66 5232–5241, 1992.

    Google Scholar 

  68. Stüber D. and Bujard H., Mol Gen Genet154 299–303, 1977.

    Google Scholar 

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Authors and Affiliations

  1. German Cancer Research Centre, Applied Tumor Virology, P.O. Box 101949, D-69009, Heidelberg, Germany

    Claus-Thomas Bock, Claus Hobe Schröder &  Hanswalter Zentgraf

  2. Privates Inst. für Immunologie und Molekulargenetik GmbH, Karlsruhe, Germany

    Peter Schranz

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  1. Claus-Thomas Bock
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  4. Hanswalter Zentgraf
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Bock, CT., Schranz, P., Schröder, C.H. et al. Hepatitis B virus genome is organized into nucleosomes in the nucleus of the infected cell. Virus Genes 8, 215–229 (1994). https://doi.org/10.1007/BF01703079

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  • DOI: https://doi.org/10.1007/BF01703079

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