Skip to content
1887

Journal of General Virology header logo Journal of General Virology

Volume 75, Issue 5

The Construction and Characterization of Poliovirus Antigen Chimeras Presenting Defined Regions of the Human T Lymphocyte Marker CD4 No Access

Abstract

Defined regions of the CDR2-like region of the T cell antigen CD4 that are implicated in the binding of the surface glycoprotein (gpl20) of human immunodeficiency virus type 1 (HIV-1) to CD4 T lymphocytes have been engineered in place of antigenic site 1 of Sabin type 1 poliovirus. The antigenic properties of the recovered chimeric virus particles were investigated using monoclonal antibodies (MAbs) and polyclonal serum to CD4. None of the MAbs tested neutralized the chimeras, presumably because they are directed against conformational determinants on the VI domain of CD4. In contrast, the three antigen chimeras were neutralized by polyclonal serum to CD4, which suggested that the CD4-derived sequences were presented in a relevant conformation. A panel of six MAbs were raised against one of the chimeras, and the epitopes were mapped by the selection of neutralization-resistant mutants and cross-neutralization studies. Five of the six MAbs reacted with soluble CD4 (sCD4) in ELISA, and one (MAb 1686) bound to CD4 expressed at the surface of HeLa cells. The high affinity interaction between gpl20 and sCD4 was not blocked by MAb 1686, and the poliovirus-CD4 chimeras did not interact with gpl20. These results demonstrate that poliovirus can be used as an epitope expression vector for the presentation of sequences in an immunodominant location on the virus particle which adopt a native or near-native conformation, and supports the findings of previous studies involving the presentation of epitopes derived from pathogens.

  • Received:
  • Accepted:
  • Published Online:
© The Journal of General Virology 1994
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-75-5-969
1994-05-01
2025-03-16
Loading full text...

Full text loading...

References

  1. Altmeyer R., Murdin A. D., Harber J. J., Wimmer E. 1991; Construction and characterization of a poliovirus/rhinovirus antigenic hybrid. Virology 184:636–644
     [Google Scholar]
  2. Arthos J., Deen K. C., Chaikin M. A., Fornwald J. A., Sathe G., Sattentau Q. J., Clapham P. R., Weiss R. A., Mcdougal J. S., Pietropaolo C., Axel R., Truneh A., Maddon P. J., Sweet R. W. 1989; Identification of the residues in human CD4 critical for the binding of HIV. Cell 57:469–481
     [Google Scholar]
  3. Brodsky M. H., Warton M., Myers R. M., Littman D. R. 1990; Analysis of the site in CD4 that binds to the HIV envelope glycoprotein. Journal of Immunology 144:3078–3086
     [Google Scholar]
  4. Burke K. L., Dunn G., Ferguson M., Minor P. D., Almond J. W. 1988; Antigen chimaeras of poliovirus as potential new vaccines. Nature; London: 33281–82
     [Google Scholar]
  5. Burke K. L., Evans D. J., Jenkins O., Meredith J., D’souza E. D. A., Almond J. W. 1989; A cassette vector for the construction of antigen chimaeras of poliovirus. Journal of General Virology 70:2475–2479
     [Google Scholar]
  6. Dedieu J. F., Ronco J., Vanderwerf S., Hogle J. M., Henin Y., Girard M. 1992; Poliovirus chimeras expressing sequences from the principal neutralization domain of human immunodeficiency virus type-1. Journal of Virology 66:3161–3167
     [Google Scholar]
  7. Evans D. J., Almond J. W. 1991; Design, construction and characterization of poliovirus antigen chimeras. Methods in Enzymology 203:387–100
     [Google Scholar]
  8. Evans D. J., Minor P. D. 1991; Growth and characterization of poliovirus antigen chimeras. In Methods in Molecular Biology 8 Practical Molecular Virology: Viral Vectors for Gene Expression pp 257–263 Collins M. K. L. Edited by Clifton, N. J.: Humana Press;
     [Google Scholar]
  9. Evans D. J., Mckeating J., Meredith J. M., Burke K. L., Katrack K., John A., Ferguson M., Minor P. D., Weiss R. A., Almond J. W. 1989; An engineered poliovirus chimaera elicits broadly reactive HIV-1 neutralizing antibodies. Nature; London: 339385–388
     [Google Scholar]
  10. Ferguson M., Minor P. D., Magrath D. I., Qi Y. -H., Spitz M., Schild G. C. 1984; Neutralization epitopes on poliovirus type 3 particles: an analysis using monoclonal antibodies. Journal of General Virology 65:197–201
     [Google Scholar]
  11. Ghetie V., Slaughter C., Wheeler H. T., Uhr J. W., Vitetta E. S. 1991; CD4 peptide-protein conjugates, but not recombinant human CD4, bind to recombinant gpl20 from the human immune-deficiency virus in the presence of serum from AIDS patients. Proceedings of the National Academy of Sciences U.S.A: 885690–5693
     [Google Scholar]
  12. Hellen C. U. T., Wimmer E. 1992a; The role of proteolytic processing in the morphogenesis of virus particles. Experientia 48:201–215
     [Google Scholar]
  13. Hellen C. U. T., Wimmer E. 1992b; Maturation of poliovirus capsid proteins. Virology 187:391–397
     [Google Scholar]
  14. Hogle J. M., Chow M., Filman D. J. 1985; Three-dimensional structure of poliovirus at 2·9 Å resolution. Science 229:1358–1365
     [Google Scholar]
  15. Jenkins O., Cason J., Burke K. L., Lunney D., Gillen A., Patel D., Mccance D. J., Almond J. W. 1990; An antigen chimera of poliovirus induces antibodies against human papillomavirus type 16. Journal of Virology 64:1201–1206
     [Google Scholar]
  16. Kitson J. D., Burke K. L., Pullen L. A., Belsham G. J., Almond J. W. 1991; Chimeric polioviruses that include sequences derived from two independent antigenic sites of foot-and-mouth disease virus (FMDV) induce neutalizing antibodies against FMDV in guinea pigs. Journal of Virology 65:3068–3075
     [Google Scholar]
  17. Landau N. R., Warton M., Littman D. R. 1988; The envelope glycoprotein of the human immunodeficiency virus binds to the immunoglobulin-like domain of CD4. Nature; London: 334159–162
     [Google Scholar]
  18. Lasky L. A., Nakamura G., Smith D. H., Fennie C., Shimasaki C., Patzer E., Berman P., Gregory T., Capon D. J. 1987; Delineation of a region of the human immunodeficiency virus type 1 gpl20 glycoprotein critical for interaction with the CD4 receptor. Cell 50:975–985
     [Google Scholar]
  19. Lemon S. M., Barclay W., Ferguson M., Murphy P., Jing L., Burke K., Wood D., Katrak K., Sangar D., Minor P. D., Almond J. W. 1992; Immunogenicity and antigenicity of chimeric picornaviruses which express hepatitis-A virus (HAV) peptide sequences-evidence for a neutralization domain near the amino terminus of VP1 of HAV. Virology 188:285–295
     [Google Scholar]
  20. Mckeating J. A., Mcknight A., Mcintosh K., Clapham P. R., Mulder C., Weiss R. A. 1989; Evaluation of human and simian immunodeficiency virus plaque and neutralization assays. Journal of General Virology 70:3327–3333
     [Google Scholar]
  21. Maddon P. J., Dalgleish A. G., Mcdougal J. S., Clapham P. R., Weiss R. A., Axel R. 1986; The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell 47:333–348
     [Google Scholar]
  22. Martin A., Wychowski C., Couderc T., Crainic R., Hogle J., Girard M. 1988; Engineering a poliovirus type 2 antigenic site on a type 1 capsid results in a chimaeric virus which is neurovirulent for mice. EMBO Journal 7:2839–2847
     [Google Scholar]
  23. Minor P. D. 1985; Growth, assay and purification of picornaviruses. In Virology: A Practical Approach, pp 25–41 Mahy B. W. J. Edited by Oxiford: IRL Press;
     [Google Scholar]
  24. Minor P. D. 1990; Antigenic structure of picornaviruses. Current Topics in Microbiology and Immunology 161:121–154
     [Google Scholar]
  25. Minor P. D., Pipkin P. A., Hockley S., Schild G. C., Almond J. W. 1984; Monoclonal antibodies which block cellular receptors of poliovirus. Virus Research 1:203–212
     [Google Scholar]
  26. Minor P. D., Ferguson M., Evans D. M. A., Almond J. W., Icenogle J. P. 1986; Antigenic structure of polioviruses of serotypes 1, 2 and 3. Journal of General Virology 67:1283–1291
     [Google Scholar]
  27. Minor P. D., Ferguson M., Phillips A., Magrath D. I., Huovilainen A., Hovi T. 1987; Conservation in vivo of protease cleavage sites in antigenic sites of poliovirus. Journal of General Virology 68:1857–1865
     [Google Scholar]
  28. Minor P. D., Ferguson M., Katrak K., Wood D., John A., Howlett J., Dunn G., Burke K., Almond J. W. 1990; Antigenic structure of chimeras of type 1 and type 3 poliovirus involving antigenic site 1. Journal of General Virology 71:2543–2551
     [Google Scholar]
  29. Minor P. D., Ferguson M., Katrak K., Wood D., John A., Howlett J., Dunn G., Burke K., Almond J. W. 1991; Antigenic structure of chimeras of type 1 and type 3 polioviruses involving antigenic sites 2,3 and 4. Journal of General Virology 72:2475–2481
     [Google Scholar]
  30. Moore J. P., Jarrett R. F. 1988; Sensitive ELISA for the gpl20 and gpl60 surface glycoproteins of HIV-1. AIDS 3:155–163
     [Google Scholar]
  31. Moore J. P., Wallace L. A., Follett E. A., Mckeating J. A. 1989; An enzyme-linked immunosorbent assay for antibodies to the envelope glycoproteins of divergent strains of HIV-1. AIDS 3:155–163
     [Google Scholar]
  32. Murdin A. D., Kameda A., Murray M. G., Wimmer E. 1991; Phenotypic characterization of antigenic hybrids of poliovirus. Microbial Pathogenesis 10:39–45
     [Google Scholar]
  33. Murray M. G., Bradley J., Yang X. F., Wimmer E., Moss E. G., Racaniello V. R. 1988a; Poliovirus host range is determined by a short amino acid sequence in neutralization antigenic site I. Science 241:213–215
     [Google Scholar]
  34. Murray M. G., Kuhn R. J., Arita M., Kawamura N., Nomoto A., Wimmer E. 1988b; Poliovirus type 1/type 3 antigenic hybrid virus constructed in vitro elicits type 1 and type 3 neutralizing antibodies in rabbits and monkeys. Proceedings of the National Academy of Sciences U.S.A: 853203–3207
     [Google Scholar]
  35. Peterson A., Seed B. 1988; Genetic analysis of monoclonal antibody and HIV binding sites on the human lymphocyte antigen CD4. Cell 54:65–72
     [Google Scholar]
  36. Racaniello V. R., Baltimore D. 1981; Cloned poliovirus complementary DNA is infectious in mammalian cells. Science 214:916–919
     [Google Scholar]
  37. Reinherz E. L., Kung P. L., Goldstein G., Schlossman S. F. 1979; Separation of functional subsets of human T cells by monoclonal antibody. Proceedings of the National Academy of Sciences U.S.A: 764061–4065
     [Google Scholar]
  38. Rico-Hesse R., Pallansch M. A., Nottay B. K., Kew O. M. 1987; Geographic distribution of wild poliovirus type 1 genotypes. Virology 160:311–322
     [Google Scholar]
  39. Rose C. S. P., Evans D. J. 1991; Poliovirus antigen chimeras. Trends in Biotechnology 9:415–421
     [Google Scholar]
  40. Ryu S. E., Kwong P. D., Truneh A., Porter T. G., Arthos J., Rosenberg M., Dai X. P., Xuong N. H., Axel R., Sweet R. W., Hendrickson W. A. 1990; Crystal structure of an HIV-binding recombinant fragment of human CD4. Nature; London: 348419–126
     [Google Scholar]
  41. Stephens P. E., Cockett M. I. 1989; The construction of a highly efficient and versatile set of mammalian expression vectors. Nucleic Acids Research 17:7110
     [Google Scholar]
  42. Van Der Werf S., Bradley J., Wimmer E., Studier F. W., Dunn J. J. 1986; Synthesis of infectious poliovirus RNA by purified T7 RNA polymerase. Proceedings of the National Academy of Sciences U.S.A: 832330–2334
     [Google Scholar]
  43. Wang J. H., Yan Y. W., Garrett T. P., Liu J. H., Rodgers D. W., Garlick R. L., Tarr G. E., Husain Y., Reinherz E. L., Harrison S. C. 1990; Atomic structure of a fragment of human CD4 containing two immunoglobulin-like domains. Nature; London: 348411–418
     [Google Scholar]
/content/journal/jgv/10.1099/0022-1317-75-5-969
Loading
The Construction and Characterization of Poliovirus Antigen Chimeras Presenting Defined Regions of the Human T Lymphocyte Marker CD4
J. Gen. Virol. 75, 969 (1994); https://doi.org/10.1099/0022-1317-75-5-969
/content/journal/jgv/10.1099/0022-1317-75-5-969
/content/journal/jgv/10.1099/0022-1317-75-5-969
Loading

Data & Media loading...

Most cited Most Cited RSS feed

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