1887

Abstract

The flavivirus envelope glycoprotein (E) is responsible for viral attachment and entry by membrane fusion. Its ectodomain is the primary target of the humoral immune response. In particular, the C-terminal Ig-like domain III of E, which is exposed at the surface of the viral particle, forms an attractive antigen for raising protective monoclonal antibodies (mAb). 9F12, a mouse mAb raised against a dengue virus (DENV) serotype 2 recombinant domain III, cross-reacts with corresponding domains from the other three DENV serotypes and also with West Nile virus. mAb 9F12 binds with nanomolar affinity to a conserved epitope that maps to the viral surface comprising residues 305, 307, 310 and 330 of the E protein. mAb 9F12 neutralizes all four DENV serotypes in plaque reduction assays. We expressed a single-chain Fv from 9F12 that retains the binding activity of the parent mAb. Adsorption and fusion inhibition assays indicate that mAb 9F12 prevents early steps of viral entry. Its virus inhibition activity and broad cross-reactivity makes mAb 9F12 a suitable candidate for optimization and humanization into a therapeutic antibody to treat severe infections by dengue.

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2009-04-01
2019-11-14
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References

  1. Allison, S. L., Schalich, J., Stiasny, K., Mandl, C. W. & Heinz, F. X. ( 2001; ). Mutational evidence for an internal fusion peptide in flavivirus envelope protein E. J Virol 75, 4268–4275.[CrossRef]
    [Google Scholar]
  2. Beasley, D. W. C. & Barrett, A. D. T. ( 2002; ). Identification of neutralizing epitopes within structural domain III of the West Nile virus envelope protein. J Virol 76, 13097–13100.[CrossRef]
    [Google Scholar]
  3. Bhardwaj, S., Holbrook, M., Shope, R. E., Barrett, A. D. & Watowich, S. J. ( 2001; ). Biophysical characterization and vector-specific antagonist activity of domain III of the tick-borne flavivirus envelope protein. J Virol 75, 4002–4007.[CrossRef]
    [Google Scholar]
  4. Bressanelli, S., Stiasny, K., Allison, S. L., Stura, E. A., Duquerroy, S., Lescar, J., Heinz, F. X. & Rey, F. A. ( 2004; ). Structure of a flavivirus envelope glycoprotein in its low-pH-induced membrane fusion conformation. EMBO J 23, 728–738.[CrossRef]
    [Google Scholar]
  5. Chen, Y. ( 1997; ). Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate. Nat Med 3, 866–871.[CrossRef]
    [Google Scholar]
  6. Chitarra, V., Alzari, P. M., Bentley, G. A., Bhat, T. N., Eisele, J. L., Houdusse, A., Lescar, J., Souchon, H. & Poljak, R. J. ( 1993; ). Three-dimensional structure of a heteroclitic antigen-antibody cross-reaction complex. Proc Natl Acad Sci U S A 90, 7711–7715.[CrossRef]
    [Google Scholar]
  7. Chu, J. J. H., Rajamanonmani, R., Li, J., Bhuvanakantham, R., Lescar, J. & Ng, M. L. ( 2005; ). Inhibition of West Nile virus entry by using a recombinant domain III from the envelope glycoprotein. J Gen Virol 86, 405–412.[CrossRef]
    [Google Scholar]
  8. Clancy, P., Xu, Y., van Heeswijk, W. C., Vasudevan, S. G. & Ollis, D. L. ( 2007; ). The domains carrying the opposing activities in adenylyltransferase are separated by a central regulatory domain. FEBS J 274, 2865–2877.[CrossRef]
    [Google Scholar]
  9. Cowieson, N. P., Wensley, B., Robin, G., Guncar, G., Forwood, J., Hume, D. A., Kobe, B. & Martin, J. L. ( 2008; ). A medium or high throughput protein refolding assay. Methods Mol Biol 426, 269–275.
    [Google Scholar]
  10. Crill, W. D. & Roehrig, J. T. ( 2001; ). Monoclonal antibodies that bind to domain III of dengue virus E glycoprotein are the most efficient blockers of virus adsorption to Vero cells. J Virol 75, 7769–7773.[CrossRef]
    [Google Scholar]
  11. Dolezal, O., Pearce, L. A., Lawrence, L. J., McCoy, A. J., Hudson, P. J. & Kortt, A. A. ( 2000; ). ScFv multimers of the anti-neuraminidase antibody NC10: shortening of the linker in single-chain Fv fragment assembled in VL to VH orientation drives the formation of dimers, trimers, tetramers and higher molecular mass multimers. Protein Eng 13, 565–574.[CrossRef]
    [Google Scholar]
  12. Gromowski, G. D., Barrett, N. D. & Barrett, A. D. ( 2008; ). Characterization of dengue complex-specific neutralizing epitopes on the envelope protein domain III of dengue 2 virus. J Virol 82, 8828–8837.[CrossRef]
    [Google Scholar]
  13. Gubler, D. J. ( 2006; ). Dengue/dengue haemorrhagic fever: history and current status. Novartis Found Symp 277, 3–16 (discussion 16–22, 71–73, 251–253).
    [Google Scholar]
  14. Halstead, S. B. ( 2007; ). Dengue. Lancet 370, 1644–1652.[CrossRef]
    [Google Scholar]
  15. Heinz, F. X. & Allison, S. L. ( 2003; ). Flavivirus structure and membrane fusion. Adv Virus Res 59, 63–97.
    [Google Scholar]
  16. Hung, J. J., Hsieh, M. T., Young, M. J., Kao, C. L., King, C. C. & Chang, W. ( 2004; ). An external loop region of domain III of dengue virus type 2 envelope protein is involved in serotype-specific binding to mosquito but not mammalian cells. J Virol 78, 378–388.[CrossRef]
    [Google Scholar]
  17. Kanai, R., Kar, K., Anthony, K., Gould, L. H., Ledizet, M., Fikrig, E., Marasco, W. A., Koski, R. A. & Modis, Y. ( 2006; ). Crystal structure of West Nile virus envelope glycoprotein reveals viral surface epitopes. J Virol 80, 11000–11008.[CrossRef]
    [Google Scholar]
  18. Karlsson, R. ( 1994; ). Real-time competitive kinetic analysis of interactions between low-molecular-weight ligands in solution and surface-immobilized receptors. Anal Biochem 221, 142–151.[CrossRef]
    [Google Scholar]
  19. Keitel, T., Kramer, A., Wessner, H., Scholz, C., Schneider-Mergener, J. & Hohne, W. ( 1997; ). Crystallographic analysis of anti-p24 (HIV-1) monoclonal antibody cross-reactivity and polyspecificity. Cell 91, 811–820.[CrossRef]
    [Google Scholar]
  20. Keller, T. H., Chen, Y. L., Knox, J. E., Lim, S. P., Ma, N. L., Patel, S. J., Sampath, A., Wang, Q. Y., Yin, Z. & Vasudevan, S. G. ( 2006; ). Finding new medicines for flaviviral targets. Novartis Found Symp 277, 102–114 (discussion 114–119, 251–253).
    [Google Scholar]
  21. Kortt, A. A., Malby, R. L., Caldwell, J. B., Gruen, L. C., Ivancic, N., Lawrence, M. C., Howlett, G. J., Webster, R. G., Hudson, P. J. & Colman, P. M. ( 1994; ). Recombinant anti-sialidase single-chain variable fragment antibody. Characterization, formation of dimer and higher-molecular-mass multimers and the solution of the crystal structure of the single-chain variable fragment/sialidase complex. Eur J Biochem 221, 151–157.[CrossRef]
    [Google Scholar]
  22. Lescar, J., Pellegrini, M., Souchon, H., Tello, D., Poljak, R. J., Peterson, N., Greene, M. I. & Alzari, P. M. ( 1995; ). Crystal structure of a cross-reaction complex between Fab F9.13.7 and guinea-fowl lysozyme. J Biol Chem 270, 18067–18076.[CrossRef]
    [Google Scholar]
  23. Lescar, J., Brynda, J., Rezacova, P., Stouracova, R., Riottot, M. M., Chitarra, V., Fabry, M., Horejsi, M., Sedlacek, J. & Bentley, G. A. ( 1999; ). Inhibition of the HIV-1 and HIV-2 proteases by a monoclonal antibody. Protein Sci 8, 2686–2696.
    [Google Scholar]
  24. Lescar, J., Roussel, A., Wien, M. W., Navaza, J., Fuller, S. D., Wengler, G., Wengler, G. & Rey, F. A. ( 2001; ). The fusion glycoprotein shell of Semliki Forest virus: an icosahedral assembly primed for fusogenic activation at endosomal pH. Cell 105, 137–148.[CrossRef]
    [Google Scholar]
  25. Lin, C. W. & Wu, S. C. ( 2003; ). A functional epitope determinant on domain III of the Japanese encephalitis virus envelope protein interacted with neutralizing-antibody combining sites. J Virol 77, 2600–2606.[CrossRef]
    [Google Scholar]
  26. Lisova, O., Hardy, F., Petit, V. & Bedouelle, H. ( 2007; ). Mapping to completeness and transplantation of a group-specific, discontinuous, neutralizing epitope in the envelope protein of dengue virus. J Gen Virol 88, 2387–2397.[CrossRef]
    [Google Scholar]
  27. Lok, S. M., Kostyuchenko, V., Nybakken, G. E., Holdaway, H. A., Battisti, A. J., Sukupolvi-Petty, S., Sedlak, D., Fremont, D. H., Chipman, P. R. & other authors ( 2008; ). Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins. Nat Struct Mol Biol 15, 312–317.[CrossRef]
    [Google Scholar]
  28. Mandl, C. W., Allison, S. L., Holzmann, H., Meixner, T. & Heinz, F. X. ( 2000; ). Attenuation of tick-borne encephalitis virus by structure-based site-specific mutagenesis of a putative flavivirus receptor binding site. J Virol 74, 9601–9609.[CrossRef]
    [Google Scholar]
  29. Martina, B. E., Koraka, P., van den Doel, P., van Amerongen, G., Rimmelzwaan, G. F. & Osterhaus, A. D. ( 2008; ). Immunization with West Nile virus envelope domain III protects mice against lethal infection with homologous and heterologous virus. Vaccine 26, 153–157.[CrossRef]
    [Google Scholar]
  30. McBride, W. J. H. & Vasudevan, S. G. ( 1995; ). Relationship of a dengue 2 isolate from Townsville, 1993, to international isolates. Commun Dis Intell 19, 522–523.
    [Google Scholar]
  31. Miller, J. L., deWet, B. J., Martinez-Pomares, L., Radcliffe, C. M., Dwek, R. A., Rudd, P. M. & Gordon, S. ( 2008; ). The mannose receptor mediates dengue virus infection of macrophages. PLoS Pathog 4, e17 [CrossRef]
    [Google Scholar]
  32. Modis, Y., Ogata, S., Clements, D. & Harrison, S. C. ( 2003; ). A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc Natl Acad Sci U S A 100, 6986–6991.[CrossRef]
    [Google Scholar]
  33. Modis, Y., Ogata, S., Clements, D. & Harrison, S. C. ( 2004; ). Structure of the dengue virus envelope protein after membrane fusion. Nature 427, 313–319.[CrossRef]
    [Google Scholar]
  34. Modis, Y., Ogata, S., Clements, D. & Harrison, S. C. ( 2005; ). Variable surface epitopes in the crystal structure of dengue virus type 3 envelope glycoprotein. J Virol 79, 1223–1231.[CrossRef]
    [Google Scholar]
  35. Navarro-Sanchez, E., Altmeyer, R., Amara, A., Schwartz, O., Fieschi, F., Virelizier, J. L., Arenzana-Seisdedos, F. & Despres, P. ( 2003; ). Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses. EMBO Rep 4, 723–728.[CrossRef]
    [Google Scholar]
  36. Nybakken, G. E., Oliphant, T., Johnson, S., Burke, S., Diamond, M. S. & Fremont, D. H. ( 2005; ). Structural basis of West Nile virus neutralization by a therapeutic antibody. Nature 437, 764–769.[CrossRef]
    [Google Scholar]
  37. Nybakken, G. E., Nelson, C. A., Chen, B. R., Diamond, M. S. & Fremont, D. H. ( 2006; ). Crystal structure of the West Nile virus envelope glycoprotein. J Virol 80, 11467–11474.[CrossRef]
    [Google Scholar]
  38. Oliphant, T., Engle, M., Nybakken, G. E., Doane, C., Johnson, S., Huang, L., Gorlatov, S., Mehlhop, E., Marri, A. & other authors ( 2005; ). Development of a humanized monoclonal antibody with therapeutic potential against West Nile virus. Nat Med 11, 522–530.[CrossRef]
    [Google Scholar]
  39. Oliphant, T., Nybakken, G. E., Austin, S. K., Xu, Q., Bramson, J., Loeb, M., Throsby, M., Fremont, D. H., Pierson, T. C. & Diamond, M. S. ( 2007; ). Induction of epitope-specific neutralizing antibodies against West Nile virus. J Virol 81, 11828–11839.[CrossRef]
    [Google Scholar]
  40. Pokidysheva, E., Zhang, Y., Battisti, A. J., Bator-Kelly, C. M., Chipman, P. R., Xiao, C., Gregorio, G. G., Hendrickson, W. A., Kuhn, R. J. & Rossmann, M. G. ( 2006; ). Cryo-EM reconstruction of dengue virus in complex with the carbohydrate recognition domain of DC-SIGN. Cell 124, 485–493.[CrossRef]
    [Google Scholar]
  41. Randolph, V. B. & Stollar, V. ( 1990; ). Low pH-induced cell fusion in flavivirus-infected Aedes albopictus cell cultures. J Gen Virol 71, 1845–1850.[CrossRef]
    [Google Scholar]
  42. 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]
  43. Rezacova, P., Lescar, J., Brynda, J., Fabry, M., Horejsi, M., Sedlacek, J. & Bentley, G. A. ( 2001; ). Structural basis of HIV-1 and HIV-2 protease inhibition by a monoclonal antibody. Structure 9, 887–895.[CrossRef]
    [Google Scholar]
  44. Roehrig, J. T., Volpe, K. E., Squires, J., Hunt, A. R., Davis, B. S. & Chang, G.-J. J. ( 2004; ). Contribution of disulfide bridging to epitope expression of the dengue type 2 virus envelope glycoprotein. J Virol 78, 2648–2652.[CrossRef]
    [Google Scholar]
  45. Sukupolvi-Petty, S., Purtha, W. E., Austin, S. K., Oliphant, T., Nybakken, G., Schlesinger, J. J., Roehrig, J. T., Gromowski, G. D., Barrett, A. D. & other authors ( 2007; ). Type- and sub-complex-specific neutralizing antibodies against domain III of dengue virus type-2 envelope protein recognize adjacent epitopes. J Virol 81, 12816–12826.[CrossRef]
    [Google Scholar]
  46. Summers, P. L., Cohen, W. H., Ruiz, M. M., Hase, T. & Eckels, K. H. ( 1989; ). Flaviviruses can mediate fusion from without in Aedes albopictus mosquito cell cultures. Virus Res 12, 383–392.[CrossRef]
    [Google Scholar]
  47. Tassaneetrithep, B., Burgess, T. H., Granelli-Piperno, A., Trumpfheller, C., Finke, J., Sun, W., Eller, M. A., Pattanapanyasat, K., Sarasombath, S. & other authors ( 2003; ). DC-SIGN (CD209) mediates dengue virus infection of human dendritic cells. J Exp Med 197, 823–829.[CrossRef]
    [Google Scholar]
  48. Thepparit, C. & Smith, D. R. ( 2004; ). Serotype-specific entry of dengue virus into liver cells: identification of the 37-kilodalton/67-kilodalton high-affinity laminin receptor as a dengue virus serotype 1 receptor. J Virol 78, 12647–12656.[CrossRef]
    [Google Scholar]
  49. Throsby, M., Geuijen, C., Goudsmit, J., Bakker, A. Q., Korimbocus, J., Kramer, R. A., Clijsters-van der Horst, M., de Jong, M., Jongeneelen, M. & other authors ( 2006; ). Isolation and characterization of human monoclonal antibodies from individuals infected with West Nile virus. J Virol 80, 6982–6992.[CrossRef]
    [Google Scholar]
  50. Thullier, P., Lafaye, P., Megret, F., Deubel, V., Jouan, A. & Mazie, J. C. ( 1999; ). A recombinant Fab neutralizes dengue virus in vitro. J Biotechnol 69, 183–190.[CrossRef]
    [Google Scholar]
  51. Thullier, P., Demangel, C., Bedouelle, H., Megret, F., Jouan, A., Deubel, V., Mazie, J.-C. & Lafaye, P. ( 2001; ). Mapping of a dengue virus neutralizing epitope critical for the infectivity of all serotypes: insight into the neutralization mechanism. J Gen Virol 82, 1885–1892.
    [Google Scholar]
  52. Tio, P. H., Jong, W. W. & Cardosa, M. J. ( 2005; ). Two dimensional VOPBA reveals laminin receptor (LAMR1) interaction with dengue virus serotypes 1, 2 and 3. Virol J 2, 25 [CrossRef]
    [Google Scholar]
  53. Volk, D. E., Beasley, D. W. C., Kallick, D. A., Holbrook, M. R., Barrett, A. D. T. & Gorenstein, D. G. ( 2004; ). Solution structure and antibody binding studies of the envelope protein domain III from the New York strain of West Nile virus. J Biol Chem 279, 38755–38761.[CrossRef]
    [Google Scholar]
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