1887

Abstract

Binding of hepatitis B virus nucleocapsids to mouse B cells leads to production of nucleocapsid-specific antibodies, class II presentation of peptides and the generation of T helper-1 immunity. This T-cell-independent activation of B cells is thought to result from cross-linking of cell-surface immunoglobulin molecules, if these contain a specific motif in the framework region 1–complementarity determining region 1 junction. In the present study, it was observed that nucleocapsids bound to different B-cell lines, an interaction that was not dependent on cell-surface-expressed immunoglobulins. Furthermore, binding to several non-B-cell lines was observed. Capsids that lacked the carboxy-terminal protamine-like domains did not bind to cells. Treatment of nucleocapsids with ribonucleases enhanced the attachment of nucleocapsids to cells. Various soluble glycosaminoglycans inhibited attachment of nucleocapsids, while treatment of cells with heparinase I also reduced binding. These observations demonstrated that the arginine-rich protamine-like regions of the core proteins are responsible for the attachment of nucleocapsids to glycosaminoglycans expressed on the plasma membranes of cells.

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2005-01-01
2019-11-12
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References

  1. Cao, T., Lazdina, U., Desombere, I., Vanlandschoot, P., Milich, D. R., Sallberg, M. & Leroux-Roels, G. ( 2001; ). Hepatitis B virus core antigen binds and activates naive human B cells in vivo: studies in a human PBL-NOD/SCID mouse model. J Virol 75, 6359–6366.[CrossRef]
    [Google Scholar]
  2. Clasper, S., Vekemans, S., Fiore, M., Plebanski, M., Wordsworth, P., David, G. & Jackson, D. G. ( 1999; ). Inducible expression of the cell surface heparan sulfate proteoglycan syndecan-2 (fibroglycan) on human activated macrophages can regulate fibroblast growth factor action. J Biol Chem 274, 24113–24123.[CrossRef]
    [Google Scholar]
  3. Console, S., Marty, C., Garcia-Echeverria, C., Schwendener, R. & Ballmer-Hofer, K. ( 2003; ). Antennapedia and HIV transactivator of transcription (TAT) “protein transduction domains” promote endocytosis of high molecular weight cargo upon binding to cell surface glycosaminoglycans. J Biol Chem 278, 35109–35114.[CrossRef]
    [Google Scholar]
  4. Fehr, T., Skratina, D., Pumpens, P. & Zinkernagel, R. M. ( 1998; ). T cell-independent type I antibody response against B cell epitopes expressed repetitively on recombinant particles. Proc Natl Acad Sci U S A 95, 9477–9481.[CrossRef]
    [Google Scholar]
  5. Freissler, E., Meyer auf der Heyde, A., David, G., Meyer, T. F. & Dehio, C. ( 2000; ). Syndecan-1 and syndecan-4 can mediate the invasion of OpaHSPG-expressing Neisseria gonorrhoeae into epithelial cells. Cell Microbiol 2, 69–82.[CrossRef]
    [Google Scholar]
  6. Fuki, I. V., Meyer, M. E. & Williams, K. J. ( 2000; ). Transmembrane and cytoplasmic domains of syndecan mediate a multi-step endocytic pathway involving detergent-insoluble membrane rafts. Biochem J 351, 607–612.[CrossRef]
    [Google Scholar]
  7. Futaki, S. ( 2002; ). Arginine-rich peptides: potential for intracellular delivery of macromolecules and the mystery of the translocation mechanisms. Int J Pharm 245, 1–7.[CrossRef]
    [Google Scholar]
  8. Gallina, A., Bonelli, F., Zentilin, L., Rindi, G., Muttini, M. & Milanesi, G. ( 1989; ). A recombinant hepatitis B core antigen polypeptide with the protamine-like domain deleted self-assembles into capsid particles but fails to bind nucleic acids. J Virol 63, 4645–4652.
    [Google Scholar]
  9. Geisberger, R., Crameri, R. & Achatz, G. ( 2003; ). Models of signal transduction through the B-cell antigen receptor. Immunology 110, 401–410.[CrossRef]
    [Google Scholar]
  10. Green, I., Christison, R., Voyce, C. J., Bundell, K. R. & Lindsay, M. A. ( 2003; ). Protein transduction domains: are they delivering? Trends Pharmacol Sci 24, 213–215.[CrossRef]
    [Google Scholar]
  11. Iozzo, R. V. ( 2001; ). Heparan sulfate proteoglycans: intricate molecules with intriguing functions. J Clin Invest 108, 165–167.[CrossRef]
    [Google Scholar]
  12. Jack, R. S., Grunwald, U., Stelter, F., Workalemahu, G. & Schütt, C. ( 1995; ). Both membrane-bound and soluble forms of CD14 bind to Gram-negative bacteria. Eur J Immunol 25, 1436–1441.[CrossRef]
    [Google Scholar]
  13. Klein, G., Giovanella, B., Westman, A., Stehlin, J. S. & Mumford, D. ( 1975; ). An EBV-genome-negative cell line established from an American Burkitt lymphoma; receptor characteristics. EBV infectibility and permanent conversion into EBV-positive sublines by in vitro infection. Intervirology 5, 319–334.
    [Google Scholar]
  14. Lazdina, U., Cao, T., Steinberg, J., Alheim, M., Pumpens, P., Peterson, D. L., Milich, D. R., Leroux-Roels, G. & Sallberg, M. ( 2001; ). Molecular basis for the interaction of the hepatitis B virus core antigen with the surface immunoglobulin receptor on naive B cells. J Virol 75, 6367–6374.[CrossRef]
    [Google Scholar]
  15. Lazdina, U., Alheim, M., Nystrom, J. & 7 other authors ( 2003; ). Priming of cytotoxic T cell responses to exogenous hepatitis B virus core antigen is B cell dependent. J Gen Virol 84, 139–146.[CrossRef]
    [Google Scholar]
  16. Manakil, J. F., Sugerman, P. B., Li, H., Seymour, G. J. & Bartold, P. M. ( 2001; ). Cell-surface proteoglycan expression by lymphocytes from peripheral blood and gingiva in health and periodontal disease. J Dent Res 80, 1704–1710.[CrossRef]
    [Google Scholar]
  17. Milich, D. R. & McLachlan, A. ( 1986; ). The nucleocapsid of hepatitis B virus is both a T-cell-independent and a T-cell-dependent antigen. Science 234, 1398–1404.[CrossRef]
    [Google Scholar]
  18. Milich, D. R., Chen, M., Schodel, F., Peterson, D. L., Jones, J. E. & Hughes, J. L. ( 1997a; ). Role of B cells in antigen presentation of the hepatitis B core. Proc Natl Acad Sci U S A 94, 14648–14653.[CrossRef]
    [Google Scholar]
  19. Milich, D. R., Schodel, F., Hughes, J. L., Jones, J. E. & Peterson, D. L. ( 1997b; ). The hepatitis B virus core and e antigens elicit different Th cell subsets: antigen structure can affect Th cell phenotype. J Virol 71, 2192–2201.
    [Google Scholar]
  20. Pumpens, P. & Grens, E. ( 1999; ). Hepatitis B core particles as a universal display model: a structure–function basis for development. FEBS Lett 442, 1–6.[CrossRef]
    [Google Scholar]
  21. Rabe, B., Vlachou, A., Pante, N., Helenius, A. & Kann, M. ( 2003; ). Nuclear import of hepatitis B virus capsids and release of the viral genome. Proc Natl Acad Sci U S A 100, 9849–9854.[CrossRef]
    [Google Scholar]
  22. Riedl, P., Stober, D., Oehninger, C., Melber, K., Reimann, R. & Schirmbeck, R. ( 2002; ). Priming Th1 immunity to viral core particles is facilitated by trace amounts of RNA bound to its arginine-rich domain. J Immunol 168, 4951–4959.[CrossRef]
    [Google Scholar]
  23. Sale, J. E. & Neuberger, M. S. ( 1998; ). TdT-accessible breaks are scattered over the immunoglobulin V domain in a constitutively hypermutating B cell line. Immunity 9, 859–869.[CrossRef]
    [Google Scholar]
  24. Saphire, A. C., Bobardt, M. D., Zhang, Z., David, G. & Gallay, P. A. ( 2001; ). Syndecans serve as attachment receptors for human immunodeficiency virus type 1 on macrophages. J Virol 75, 9187–9200.[CrossRef]
    [Google Scholar]
  25. Seeger, C. & Mason, W. S. ( 2000; ). Hepatitis B virus biology. Microbiol Mol Biol Rev 64, 51–68.[CrossRef]
    [Google Scholar]
  26. Simons, M. & Horowitz, A. ( 2001; ). Syndecan-4-mediated signalling. Cell Signal 13, 855–862.[CrossRef]
    [Google Scholar]
  27. Steinfeld, R., Van den Berghe, H. & David, G. ( 1996; ). Stimulation of fibroblast growth factor receptor-1 occupancy and signaling by cell surface-associated syndecans and glypican. J Cell Biol 133, 405–416.[CrossRef]
    [Google Scholar]
  28. Storni, T., Ruedl, C., Schwarz, K., Schwendener, R. A., Renner, W. A. & Bachmann, M. F. ( 2004; ). Nonmethylated CG motifs packaged into virus-like particles induce protective cytotoxic T cell responses in the absence of systemic side effects. J Immunol 172, 1777–1785.[CrossRef]
    [Google Scholar]
  29. Tkachenko, E., Lutgens, E., Stan, R. V. & Simons, M. ( 2004; ). Fibroblast growth factor 2 endocytosis in endothelial cells proceeds via syndecan-4-dependent activation of Rac1 and a Cdc42-dependent macropinocytic pathway. J Cell Sci 117, 3189–3199.[CrossRef]
    [Google Scholar]
  30. Turnbull, J., Powell, A. & Guimond, S. ( 2001; ). Heparan sulfate: decoding a dynamic multifunctional cell regulator. Trends Cell Biol 11, 75–82.[CrossRef]
    [Google Scholar]
  31. Tyagi, M., Rusnati, M., Presta, M. & Giacca, M. ( 2001; ). Internalization of HIV-1 tat requires cell surface heparan sulfate proteoglycans. J Biol Chem 276, 3254–3261.[CrossRef]
    [Google Scholar]
  32. Valentine, M. A. & Licciardi, K. A. ( 1992; ). Rescue from anti-IgM-induced programmed cell death by the B cell surface proteins CD20 and CD40. Eur J Immunol 22, 3141–3148.[CrossRef]
    [Google Scholar]
  33. Van der Voort, R., Keehnen, R. M. J., Beuling, E. A., Spaargaren, M. & Pals, S. T. ( 2000; ). Regulation of cytokine signaling by B cell antigen receptor and CD40-controlled expression of heparan sulfate proteoglycans. J Exp Med 192, 1115–1124.[CrossRef]
    [Google Scholar]
  34. Vanlandschoot, P., Cao, T. & Leroux-Roels, G. ( 2003; ). The nucleocapsid of the hepatitis B virus: a remarkable immunogenic structure. Antiviral Res 60, 67–74.[CrossRef]
    [Google Scholar]
  35. Watts, N. R., Conway, J. F., Cheng, N., Stahl, S. J., Belnap, D. M., Steven, A. C. & Wingfield, P. T. ( 2002; ). The morphogenic linker peptide of HBV capsid protein forms a mobile array on the interior surface. EMBO J 21, 876–884.[CrossRef]
    [Google Scholar]
  36. Wingfield, P. T., Stahl, S. J., Williams, R. W. & Steven, A. C. ( 1995; ). Hepatitis core antigen produced in Escherichia coli: subunit composition, conformational analysis and in vitro capsid assembly. Biochemistry 34, 4919–4932.[CrossRef]
    [Google Scholar]
  37. Wynne, S. A., Crowther, R. A. & Leslie, A. G. ( 1999; ). The crystal structure of the human hepatitis B virus capsid. Mol Cell 3, 771–780.[CrossRef]
    [Google Scholar]
  38. Yamashita, Y., Oritani, K., Miyoshi, E. K., Wall, R., Bernfield, M. & Kincade, P. W. ( 1999; ). Syndecan-4 is expressed by B lineage lymphocytes and can transmit a signal for formation of dendritic processes. J Immunol 162, 5940–5948.
    [Google Scholar]
  39. Zhang, W., Bardwell, P. D., Woo, C. J., Poltoratsky, V., Scharff, M. D. & Martin, A. ( 2001a; ). Clonal instability of V region hypermutation in the Ramos Burkitt's lymphoma cell line. Int Immunol 13, 1175–1184.[CrossRef]
    [Google Scholar]
  40. Zhang, Z., Coomans, C. & David, G. ( 2001b; ). Membrane heparan sulfate proteoglycan-supported FGF2-FGFR1 signaling. Evidence in support of the “cooperative end structures” model. J Biol Chem 276, 41921–41929.[CrossRef]
    [Google Scholar]
  41. Zimmermann, P. & David, G. ( 1999; ). The syndecans, tuners of transmembrane signaling. FASEB J 13 (Suppl.), S91–S100.
    [Google Scholar]
  42. Zlotnick, A., Cheng, N., Stahl, S. J., Conway, J. F., Steven, A. C. & Wingfield, P. T. ( 1997; ). Localization of the C terminus of the assembly domain of hepatitis B virus capsid protein: implications for morphogenesis and organization of encapsidated RNA. Proc Natl Acad Sci U S A 94, 9556–9561.[CrossRef]
    [Google Scholar]
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