1887

Abstract

Dengue virus infections are a growing public health concern and strategies to control the spread of the virus are urgently needed. The murine monoclonal antibody 4E11 might be of interest, since it neutralizes dengue viruses of all serotypes by binding to the 296–400 segment of the major dengue virus envelope glycoprotein (DE). When phage-displayed peptide libraries were screened by affinity for 4E11, phage clone C1 was selected with a 50% frequency. C1 shared three of nine residues with DE and showed significant reactivity to 4E11 in ELISA. C1-induced antibodies cross-reacted with DE in mice, suggesting that it was a structural equivalent of the native epitope of 4E11 on DE. Accordingly, 4E11 bound to the DE synthetic peptide and this reaction was inhibited by DE. Moreover, DE could block dengue virus infection of target cells in an assay. A three-dimensional model of DE revealed that the three amino acids shared by DE and C1 were exposed to the solvent and suggested that most of the amino acids comprising the 4E11 epitope were located in the DE region. Since 4E11 blocked the binding of DE to heparin, which is a highly sulfated heparan sulfate (HSHS) molecule, 4E11 may act by neutralizing the interaction of DE with target cell-displayed HSHS. Our data suggest that the DE segment is critical for the infectivity of all dengue virus serotypes and that molecules that block the binding of DE to HSHS may be antiviral reagents of therapeutic interest.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-82-8-1885
2001-08-01
2019-10-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/82/8/0821885a.html?itemId=/content/journal/jgv/10.1099/0022-1317-82-8-1885&mimeType=html&fmt=ahah

References

  1. Biozzi, G., Mouton, D., Heumann, A. M., Bouthillier, Y., Stiffel, C. & Mevel, J. C. ( 1979; ). Genetic analysis of antibody responsiveness to sheep erythrocytes in crosses between lines of mice selected for high or low antibody synthesis. Immunology 36, 427-438.
    [Google Scholar]
  2. Callahan, L. N., Phelan, M., Mallinson, M. & Norcross, M. A. ( 1991; ). Dextran sulfate blocks antibody binding to the principal neutralizing domain of human immunodeficiency virus type 1 without interfering with gp120–CD4 interactions. Journal of Virology 65, 1543-1550.
    [Google Scholar]
  3. Chen, Y., Maguire, T., Hileman, R. E., Fromm, J. R., Esko, J. D., Linhardt, R. J. & Marks, R. M. ( 1997; ). Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate. Nature Medicine 3, 866-871.[CrossRef]
    [Google Scholar]
  4. Christian, R. B., Zuckermann, R. N., Kerr, J. M., Wang, L. & Malcolm, B. A. ( 1992; ). A simplified method for construction, assessment and rapid screening of peptide libraries in bacteriophage. Journal of Molecular Biology 227, 711-718.[CrossRef]
    [Google Scholar]
  5. Cribier, B., Schmitt, C., Kirn, A. & Stoll-Keller, F. ( 1998; ). Inhibition of hepatitis C virus adsorption to peripheral blood mononuclear cells by dextran sulfate. Archives of Virology 143, 375-379.[CrossRef]
    [Google Scholar]
  6. Demangel, C., Lafaye, P. & Mazie, J. C. ( 1996; ). Reproducing the immune response against the Plasmodium vivax merozoite surface protein 1 with mimotopes selected from a phage-displayed peptide library. Molecular Immunology 33, 909-916.[CrossRef]
    [Google Scholar]
  7. Demangel, C., Rouyre, S., Alzari, P. M., Nato, F., Longacre, S., Lafaye, P. & Mazie, J. C. ( 1998; ). Phage-displayed mimotopes elicit monoclonal antibodies specific for a malaria vaccine candidate. Biological Chemistry 379, 65-70.
    [Google Scholar]
  8. Despres, P., Flamand, M., Ceccaldi, P. E. & Deubel, V. ( 1996; ). Human isolates of dengue type 1 virus induce apoptosis in mouse neuroblastoma cells. Journal of Virology 70, 4090-4096.
    [Google Scholar]
  9. Falconar, A. K. I. ( 1996; ). The dengue virus nonstructural 1 protein (NS1) generates antibodies to common epitopes on human blood clotting, integrin/adhesin proteins and binds to human endothelial cells: potential implications in haemorrhagic fever pathogenesis. Archives of Virology 142, 897-916.
    [Google Scholar]
  10. Felici, F., Luzzago, A., Monaci, P., Nicosia, A., Sollazzo, M. & Traboni, C. ( 1995; ). Peptide and protein display on the surface of filamentous bacteriophage. Biotechnology Annual Review 1, 149-183.
    [Google Scholar]
  11. Flynn, S. J. & Ryan, P. ( 1996; ). The receptor-binding domain of pseudorabies virus glycoprotein gC is composed of multiple discrete units that are functionally redundant. Journal of Virology 70, 1355-1364.
    [Google Scholar]
  12. Friguet, B., Djavadi-Ohaniance, L., Bussard, A. & Goldberg, M. E. ( 1985; ). Measurement of the affinity constant in solution of antigen–antibody complexes by enzyme-linked immunosorbent assay. Journal of Immunological Methods 77, 305-319.[CrossRef]
    [Google Scholar]
  13. Halstead, S. B. & O’Rourke, E. J. ( 1977; ). Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody. Journal of Experimental Medicine 146, 201-217.[CrossRef]
    [Google Scholar]
  14. Herold, B. C., Gerber, S. I., Polonsky, T., Belval, B. J., Shaklee, P. N. & Holme, K. ( 1995; ). Identification of structural features of heparin required for inhibition of herpes simplex virus type 1 binding. Virology 206, 1108-1110.[CrossRef]
    [Google Scholar]
  15. Hilgard, P. & Stockert, R. ( 2000; ). Heparan sulfate proteoglycans initiate dengue virus infection of hepatocytes. Hepatology 35, 1069-1077.
    [Google Scholar]
  16. Igarashi, A. ( 1997; ). Impact of dengue virus infection and its control. FEMS Immunology and Medical Microbiology 18, 291-300.[CrossRef]
    [Google Scholar]
  17. Lafaye, P., Nato, F., Mazié, J.-C. & Doyen, N. ( 1995; ). Similar binding properties for a neutralizing anti-tetanus toxoid human monoclonal antibody and its bacterially expressed Fab. Research in Immunology 146, 373-382.[CrossRef]
    [Google Scholar]
  18. Lopalco, L., Ciccomascolo, F., Lanza, P., Zopetti, G., Caramazza, I., Leoni, F., Beretta, A. & Siccardi, A. G. ( 1994; ). Anti-HIV type 1 properties of chemically modified heparins with diminished anticoagulant activity. AIDS Research and Human Retroviruses 10, 787-793.
    [Google Scholar]
  19. Lyon, M., Deakin, J. A. & Gallagher, J. T. ( 1994; ). Liver heparan sulfate structure. Journal of Biological Chemistry 269, 11208-11215.
    [Google Scholar]
  20. Mason, P., McAda, P. C., Mason, T. L. & Fournier, M. J. ( 1987; ). Sequence of the dengue 1 virus genome in the region encoding the three structural proteins and the major nonstructural protein NS1. Virology 161, 262-267.[CrossRef]
    [Google Scholar]
  21. Mégret, F., Hugnot, J. P., Falconar, A., Gentry, M. K., Morens, D. M., Murray, J. M., Schlesinger, J. J., Wright, P. J., Young, P., van Regenmortel, M. H. V. & Deubel, V. ( 1992; ). Use of recombinant fusion proteins and monoclonal antibodies to define linear and discontinuous antigenic sites on the dengue virus envelope glycoprotein. Virology 187, 480-491.[CrossRef]
    [Google Scholar]
  22. Morens, D. M. & Halstead, S. B. ( 1990; ). Measurement of antibody-dependent infection enhancement of four dengue virus serotypes by monoclonal and polyclonal antibodies. Journal of General Virology 71, 2909-2914.[CrossRef]
    [Google Scholar]
  23. Murgue, B., Cassar, O., Guigon, M. & Chungue, E. ( 1997; ). Dengue virus inhibits human hematopoietic progenitor growth in vitro. Journal of Infectious Diseases 175, 1497-1501.[CrossRef]
    [Google Scholar]
  24. Needleman, S. B. & Wunsh, C. D. ( 1970; ). A general method applicable to the search for similarities in the amino acid sequence of two proteins. Journal of Molecular Biology 48, 443-453.[CrossRef]
    [Google Scholar]
  25. Patel, M., Yanagishita, M., Roderiquez, G., Bou-Habib, D. C., Oravecz, T., Hascall, V. C. & Norcross, M. A. ( 1993; ). Cell-surface heparan sulfate proteoglycan mediates HIV-1 infection of T-cell lines. AIDS Research and Human Retroviruses 9, 167-174.[CrossRef]
    [Google Scholar]
  26. Rey, F. A., Heinz, F. X., Mandl, C., Kunz, C. & Harrison, S. C. ( 1995; ). The envelope glycoprotein from tick-borne encephalitis virus at 2 Å resolution. Nature 375, 291-298.[CrossRef]
    [Google Scholar]
  27. Sanger, F., Nicklen, S. & Coulson, A. R. ( 1977; ). DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, USA 74, 5463-5467.[CrossRef]
    [Google Scholar]
  28. Thullier, P., Lafaye, P., Mégret, F., Deubel, V., Jouan, A. & Mazié, J. C. ( 1999; ). A recombinant Fab neutralizes dengue virus in vitro. Journal of Biotechnology 69, 183-190.[CrossRef]
    [Google Scholar]
  29. Tolou, H., Durand, J.-P. & Pisano, M.-R. ( 1997; ). Current status of dengue. Médecine Tropicale 57, 70S–73S (in French).
    [Google Scholar]
  30. Trybala, E., Bergstrom, T., Spillman, D., Svennerholm, B., Flynn, S. J. & Ryan, P. ( 1998; ). Interaction between pseudorabies and heparin/heparan sulfate. Pseudorabies virus mutants differ in their interaction with heparin/heparan sulfate when altered for specific glycoprotein C heparin-binding domain. Journal of Biological Chemistry 273, 5047-5052.[CrossRef]
    [Google Scholar]
  31. Vriend, G. ( 1990; ). WHAT IF: a molecular modelling and drug design program. Journal of Molecular Graphics 8, 52-56.[CrossRef]
    [Google Scholar]
  32. WuDunn, D. & Spear, P. G. ( 1989; ). Initial interaction of herpes simplex virus with cells is binding to heparan sulfate. Journal of Virology 63, 52-58.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-82-8-1885
Loading
/content/journal/jgv/10.1099/0022-1317-82-8-1885
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error