1887

Abstract

The neutralizing activity and fusion-inhibition activity per unit weight of immunoglobulin were determined for each of a panel of 20 monoclonal antibodies (MAbs) to the fusion (F) protein of respiratory syncytial (RS) virus. Neutralization did not correlate with fusion-inhibiting activity, suggesting that the F protein plays at least two independent, antibody-sensitive roles in viral infection. Antibodies with the highest biological activity against A2, a subgroup A strain of RS virus, neutralized a subgroup B strain (8/60) poorly, suggesting a degree of antigenic variation that may be important in human infection.

All but one fusion-inhibiting MAb bound to protein blots and binding was mapped to two areas on overlapping F protein fragments. One MAb with relatively poor fusion-inhibiting activity bound only to fragments C-terminal of amino acid 384, the remainder bound only to fragments containing residues 253 to 289. MAbs directed to the latter site were heterogeneous in neutralizing activity, subgroup specificity and fusion- inhibiting activity. These variations between MAbs could not be accounted for by differences in their binding avidities. We suggest that this binding site is not the complete antibody epitope which probably includes conformation-dependent elements.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-75-10-2813
1994-10-01
2022-12-01
Loading full text...

Full text loading...

/deliver/fulltext/jgv/75/10/JV0750102813.html?itemId=/content/journal/jgv/10.1099/0022-1317-75-10-2813&mimeType=html&fmt=ahah

References

  1. Anderson L. 1990; Strains of respiratory syncytial virus: implications for vaccine development. In Medical Virology 9 pp. 187–205 de la Maza L. M., Peterson E. M. Edited by New York: Plenum Press;
    [Google Scholar]
  2. Anderson L. J., Hierholzer J. C., Stone Y. O., Tsou C., Fernie B. F. 1986; Identification of epitopes on respiratory syncytial virus proteins by competitive binding immunoassay. Journal of Clinical Microbiology 23:475–480
    [Google Scholar]
  3. Arbiza J., Taylor G., López J. A., Furze J., Wyld S., Whyte P., Stott E. J., Wertz G., Sullender G., Trudel M., Melero J. A. 1992; Characterization of two antigenic sites recognized by neutralizing monoclonal antibodies directed against the fusion glycoprotein of human respiratory syncytial virus. Journal of General Virology 73:2225–2234
    [Google Scholar]
  4. Arumugham R. G., Hildreth S. W., Paradiso P. R. 1989; Interproteindisulphide bonding between F and G glycoproteins of human respiratory syncytial virus. Archives of Virology 105:65–79
    [Google Scholar]
  5. Baybutt H. N., Pringle C. R. 1987; Molecular cloning and sequencing of the F and 22K membrane protein genes of the RSS-2 strain of respiratory syncytial virus. Journal of General Virology 68:2789–2796
    [Google Scholar]
  6. Beeler J. A., van Wyke Coelingh K. 1989; Neutralization epitopes of the F glycoprotein of respiratory syncytial virus: effect of mutation upon fusion function. Journal of Virology 63:2941–2950
    [Google Scholar]
  7. Bourgeois C., Corvaisier C., Bour J. B., Kohli E., Pothier P. 1991; Use of synthetic peptides to locate neutralizing antigenic domains on the fusion protein of respiratory syncytial virus. Journal of General Virology 72:1051–1058
    [Google Scholar]
  8. Collins P. L., Mottet G. 1991; Post-translational processing and oligomerization of the fusion glycoprotein of human respiratory syncytial virus. Journal of General Virology 72:3095–3101
    [Google Scholar]
  9. Collins P. L., Huang Y. T., Wertz G. W. 1984; Nucleotide sequence of the gene encoding the fusion (F) glycoprotein of human respiratory syncytial virus. Proceedings of the National Academy of Sciences, U.S.A 81:7683–7687
    [Google Scholar]
  10. Darst S. A., Robertson C. R., Berzovsky J. A. 1988; Adsorption of the protein antigen myoglobin affects the binding of conformation-specific monoclonal antibodies. Biophysics Journal 53:533–539
    [Google Scholar]
  11. García-Barreno B., Palomo C., Peñas C., Delgado T., Pérez-Breña P., Melero J. A. 1989; Marked differences in the antigenic structure of human respiratory syncytial virus F and G glycoproteins. Journal of Virology 63:925–932
    [Google Scholar]
  12. Himes S. R., Gershwin L. J. 1992; Bovine respiratory syncytial virus fusion protein gene: sequence analysis of cDNA and expression using a baculovirus vector. Journal of General Virology 73:1563–1567
    [Google Scholar]
  13. Johnson P. R., Collins P. L. 1988; The fusion glycoproteins of human respiratory syncytial virus of subgroups A and B: sequence conservation provides a structural basis for antigenic relatedness. Journal of General Virology 69:2623–2628
    [Google Scholar]
  14. Johnson P. R., Olmsted R. A., Price G. A., Murphy B. R., Alling D. W., Walsh E. E., Collins P. L. 1987; Antigenic relatedness between glycoproteins of human respiratory syncytial virus subgroups A and B: evaluation of the contribution of F and G glycoproteins to immunity. Journal of Virology 61:3163–3166
    [Google Scholar]
  15. Lerch R. A., Stott E. J., Wertz G. W. 1989; Characterization of bovine respiratory syncytial virus proteins and mRNAs and the generation of cDNA clones to the viral mRNAs. Journal of Virology 63:833–840
    [Google Scholar]
  16. López J. A., Villanueva N., Melero J. A., Portela A. 1988; Nucleotide sequence of the fusion and phosphoprotein genes of human respiratory syncytial (RS) virus Long strain: evidence of subtype genetic heterogeneity. Virus Research 10:249–262
    [Google Scholar]
  17. Lounsbach G. R., Bourgeois C., West W. H. L., Robinson J. W., Carter M. J., Toms G. L. 1993; The binding of neutralizing monoclonal antibodies to regions of the fusion protein of respiratory syncytial virus expressed in Escherichia coli . Journal of General Virology 74:2559–2565
    [Google Scholar]
  18. Mcintosh K., Chanock R. M. 1990; Respiratory syncytial virus. In Virology, 2nd edn. pp. 1045–1072 Fields B. N., Knipe D. M. Edited by New York: Raven Press;
    [Google Scholar]
  19. Martin-Gallardo A., Fien K. A., Hu B. T., Farley J. F., Seid R., Collins P. L., Hildreth S. W., Paradiso P. R. 1991; Expression of the F glycoprotein gene from human respiratory syncytial virus in Escherichia coli: mapping of a fusion inhibiting epitope. Virology 184:428–432
    [Google Scholar]
  20. Morrison T. G., Portner A. 1991; Structure, function, and intracellular processing of the glycoproteins of Paramyxoviridae . In The Paramyxoviruses pp. 347–382 Kingsbury D. W. Edited by New York: Plenum Press;
    [Google Scholar]
  21. Mutson M. A., Örvell C., Rafnar B., Norrby E. 1985; Two distinct subtypes of human respiratory syncytial virus. Journal of General Virology 66:2111–2124
    [Google Scholar]
  22. Mulenaer P. M., Henderson F. W., Hemming V. G., Walsh E. E., Anderson L. J., Prince G. A., Murphy B. R. 1991; Group-specific serum antibody responses in children with primary and recurrent respiratory syncytial virus infections. Journal of Infectious Diseases 164:15–21
    [Google Scholar]
  23. Richards K. L. 1994 The use of monoclonal antibodies to investigate antigenic variation in subgroup B respiratory syncytial virus Ph.D. thesis University of Sunderland:
    [Google Scholar]
  24. Routledge E. G., Mcquilun J., Samson A. C. R., Toms G. L. 1985; The development of monoclonal antibodies to respiratory syncytial virus and their use in diagnosis by indirect immunofluorescence. Journal of Medical Virology 15:305–320
    [Google Scholar]
  25. Routledge E. G., Willcocks M. M., Samson A. C. R., Morgan L. L., Scott R., Anderson J. J., Toms G. L. 1988; The purification of four respiratory syncytial virus proteins and their evaluation as protective agents against experimental infection of BALB/c mice. Journal of General Virology 69:293–303
    [Google Scholar]
  26. Samson A. C. R., Willcocks M. M., Routledge E. G., Morgan L. A., Toms G. L. 1986; A neutralizing monoclonal antibody to respiratory syncytial virus which binds to both F1 and F2 components of the fusion protein. Journal of General Virology 67:1479–1483
    [Google Scholar]
  27. Schulman M., Wilde C. D., Kohler G. 1978; A better cell line for making hybridomas secreting specific antibodies. Nature; London: 276269–271
    [Google Scholar]
  28. Spriggs M. K., Olmsted R. A., Venkatesan S., Coligan J. E., Collins P. L. 1986; Fusion glycoprotein of human parainfluenza virus type 3: nucleotide sequence of the gene, direct identification of the cleavage-activation site and comparison with other paramyxoviruses. Virology 152:241–251
    [Google Scholar]
  29. Taylor G., Stott E. J., Bew M., Fernie B. F., Cote P. J., Collins A. P., Hughes M., Jebbett J. J. 1984; Monoclonal antibodies protect against respiratory syncytial virus infection in mice. Immunology 52:137–142
    [Google Scholar]
  30. Taylor G., Stott E. J., Furze J., Ford J., Sopp P. 1992; Protective epitopes on the fusion protein of respiratory syncytial virus recognized by murine and bovine monoclonal antibodies. Journal of General Virology 73:2217–2223
    [Google Scholar]
  31. Trudel M., Nadon F., Seguin C., Dionne G., Lacroix M. 1987a; Identification of a synthetic peptide as part of a major neutralization epitope of respiratory syncytial virus. Journal of General Virology 68:2273–2280
    [Google Scholar]
  32. Trudel M., Nadon F., Seguin C., Payment P., Talbot P. 1987b; Respiratory syncytial virus fusion glycoprotein: further characterization of a major epitope involved in virus neutralization. Canadian Journal of Microbiology 33:933–938
    [Google Scholar]
  33. Ueba O. 1978; Respiratory syncytial virus. 1. Concentration and purification of the infectious virus. ActaMedica Okayama 32:265–272
    [Google Scholar]
  34. Van Heyningen, Van Heyningen. 1987; Ranking the affinities of monoclonal antibodies. In Methods of Hybridoma Formation pp. 399–412 Bartal A. H., Hirshaut Y. Edited by Humana Press; Clifton, New Jersey:
    [Google Scholar]
  35. Walsh E. E., Hruska J. 1983; Monoclonal antibodies to respiratory syncytial virus proteins: identification of the fusion protein. Journal of Virology 47:171–177
    [Google Scholar]
  36. Wang C., Raghu G., Morrison T., Peebles M. 1992; Intracellular processing of the paramyxovirus F protein: critical role of the predicted amphipathic alpha helix adjacent to the fusion domain. Journal of Virology 66:4161–4169
    [Google Scholar]
  37. Wertz G. W., Stott E. J., Young K. K. Y., Anderson K., Ball A. 1987; Expression of the fusion protein of human respiratory syncytial virus from recombinant vaccinia virus vectors and protection of vaccinated mice. Journal of Virology 61:293–301
    [Google Scholar]
  38. Yazici Z. 1993 The production of murine and human monoclonal antibodies to the fusion protein of respiratory syncytial virus Ph.D. thesis University of Newcastle upon Tyne:
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-75-10-2813
Loading
/content/journal/jgv/10.1099/0022-1317-75-10-2813
Loading

Data & Media loading...

Most cited this month 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