1887

Abstract

Foot-and-mouth disease virus (FMDV) of serotype C (isolate C-S8c1) was cleaved by trypsin at the Arg-Gly-Asp (RGD) motif, which is involved both in attachment of FMDV to cells and in recognition of a major antigenic site (site A) by antibodies. Though 99.4% of the RGD moieties were cleaved, the virus remained infectious. A synthetic peptide which represented the sequence of the VP1 G-H loop of C-S8c1, including the RGD motif, greatly inhibited FMDV attachment to cells. The same peptide inhibited, very effectively and to the same extent (50% inhibition at about 1 µ), the infectivity of both intact and trypsin-treated virus. Replacement of Asp with Glu at the RGD motif abolished the inhibitory effects of the peptide. Thus, the RGD motif is involved in the infectivity of both intact and RGD-cleaved serotype C FMDV. Trypsin treatment did not affect the reactivity of the virus with some monoclonal antibodies (MAbs) directed to site A whose epitopes involve mainly residues contiguous to the cleaved bond, but diminished the reactivity with site A MAbs whose epitopes include the RGD sequence and flanking residues. However, high concentrations of any site A MAb tested neutralized close to 100% of the infectious trypsin-treated virus. We propose that, in spite of covalent cleavage, the high number of intramolecular non-covalent interactions observed within the G-H loop of FMDV C-S8c1 (complexed to antibody) may hold the RGD in a nearly correct conformation and allow — albeit with reduced affinity — antibody and cell receptor recognition of RGD-cleaved FMDV.

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1996-02-01
2022-01-27
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References

  1. Acharya R., Fry E., Stuart D., Fox G., Rowlands D., Brown F. 1989; The three-dimensional structure of foot-and-mouth disease virus at 2.9 Å resolution. Nature 337:709–716
    [Google Scholar]
  2. Baxt B., Becker Y. 1990; The effect of peptides containing the arginine-glycine-aspartic acid sequence on the adsorption of foot- and-mouth disease virus to tisue culture cells. Virus Genes 4:73–83
    [Google Scholar]
  3. Baxt B., Vakharia V., Moore D. M., Franke A. J., Morgan D. O. 1989; Analysis of neutralizing antigenic sites on the surface of type A12 foot-and-mouth disease virus. Journal of Virology 63:2143–2151
    [Google Scholar]
  4. Berinstein A., Roivainen M., Hovi T., Mason P. W., Baxt B. 1995; Antibodies to the vitronectin receptor (integrin αvβ3) inhibit binding and infection of foot-and-mouth disease virus to cultured cells. Journal of Virology 69:2664–2666
    [Google Scholar]
  5. Bittle J. L., Houghten R. A., Alexander H., Shinnick T. M., Sutcliffe J. G., Lerner R. A., Rowlands D. J., Brown F. 1982; Protection against foot-and-mouth disease by immunization with a chemically synthesized peptide predicted from the viral nucleotide sequence. Nature 298:30–33
    [Google Scholar]
  6. Bolwell C., Clarke B. E., Parry N. R., Ouldridge E. J., Brown F., Rowlands D. J. 1989; Epitope mapping of foot-and-mouth disease virus with neutralizing monoclonal antibodies. Journal of General Virology 70:59–68
    [Google Scholar]
  7. Carreño C., Roig X., Cairo J., Camarero J., Mateu M. G., Domingo E., Giralt E., Andreu D. 1992; Studies on antigenic variability of C strains of foot-and-mouth disease virus by means of synthetic peptides and monoclonal antibodies. International Journal of Peptide Protein Research 39:41–47
    [Google Scholar]
  8. da Silva J. L., Kanashiro M. M., de Brum D. L. 1993; Production and characterization of monoclonal antibodies against foot-and-mouth disease virus. Boletin del Centro Panamericano de Fiebre Aftosa 59:1–8
    [Google Scholar]
  9. De la Torre J. C., Martinez-Salas E., Diez J., Villaverde A., Gebauer F., Rocha E., Davila M., Domingo E. 1988; Coevolution of cells and viruses in a persistent infection of foot-and- mouth disease virus in cell culture. Journal of Virology 62:2050–2058
    [Google Scholar]
  10. Díez J., Davila M., Escarmis C., Mateu M. G., Dominguez J., Perez J. J., Giralt E., Melero J. A., Domingo E. 1990; Unique amino acid substitutions in the capsid proteins of foot-and- mouth disease virus from a persistent infection in cell culture. Journal of Virology 64:5519–5528
    [Google Scholar]
  11. Domingo E., Mateu M. G., Martinez M. A., Dopazo J., Moya A., Sobrino F. 1990; Genetic variability and antigenic diversity of foot-and-mouth disease virus. In Applied Virology Research vol 2 pp 233–266 Edited by Kurstak E., Marusyk R. G., Murphy F. A., van Regenmortel M. H. V. New York: Plenum Press;
    [Google Scholar]
  12. Feigelstock D., Mateu M. G., Piccone M. E., de Simone F., Brocchi E., Domingo E., Palma E. L. 1992; Extensive antigenic diversification of foot-and-mouth disease virus by amino acid substitutions outside the major antigenic site. Journal of General Virology 73:3307–3311
    [Google Scholar]
  13. Fox G., Parry N., Barnett P. V., McGinn B., Rowlands D. J., Brown F. 1989; The cell attachment site on foot-and-mouth disease virus includes the amino acid sequence RGD (arginineglycine-aspartic acid). Journal of General Virology 70:625–637
    [Google Scholar]
  14. Kitson J. D. A., McCahon D., Belsham G. J. 1990; Sequence analysis of monoclonal antibody resistant mutants of type O foot- and-mouth disease virus: evidence for the involvement of the three surface exposed capsid proteins in four antigenic sites. Virology 179:26–34
    [Google Scholar]
  15. Lea S., Hernandez J., Blakemore W., Brocchi E., Curry S., Domingo E., Fry E., Abu-Ghazaleh R., King A. M. Q., Newman J., Stuart D., Mateu M. G. 1994; The structure and antigenicity of a serotype C foot-and-mouth disease virus. Structure 2:123–139
    [Google Scholar]
  16. Logan D., Abu-Ghazaleh R., Blakemore W., Curry S., Jackson T., King A., Lea S., Lewis R., Newman J., Parry N., Rowlands D., Stuart D., Fry E. 1993; Structure of a major immunogenic site of foot-and-mouth disease virus. Nature 362:566–568
    [Google Scholar]
  17. Mason P. W., Rieder E., Baxt B. 1994; RGD sequence of foot- and-mouth disease virus is essential for infecting cells via the natural receptor but can be bypassed by an antibody-dependent enhancement pathway. Proceedings of the National Academy of Sciences, USA 91:1932–1936
    [Google Scholar]
  18. Mateu M. G. 1995; Antibody recognition of picornaviruses and escape from neutralization: a structural view. Virus Research 38:1–24
    [Google Scholar]
  19. Mateu M. G., Rocha E., Vicente O., Vayreda F., Navalpotro C., Andreu D., Pedroso E., Giralt E., Enjuanes L., Domingo E. 1987; Reactivity with monoclonal antibodies of viruses from an episode of foot-and-mouth disease. Virus Research 8:261–274
    [Google Scholar]
  20. Mateu M. G., da Silva J. L., Rocha E., de Brum D. L., Alonso A., Enjuanes L., Domingo E., Barahona H. 1988; Extensive antigenic heterogeneity of foot-and-mouth disease virus of serotype C. Virology 167:113–124
    [Google Scholar]
  21. Mateu M. G., Martinez M. A., Rocha E., Andreu D., Pareio J., Giralt E., Sobrino F., Domingo E. 1989; Implications of a quasispecies genome structure: effect of frequent, naturally occurring amino acid substitutions on the antigenicity of foot-and-mouth disease virus. Proceedings of the National Academy of Sciences, USA 86:5883–5887
    [Google Scholar]
  22. Mateu M. G., Martinez M. A., Capucci L., Andreu D., Giralt E., Sobrino F., Brocchi E., Domingo E. 1990; A single amino acid substitution affects multiple overlapping epitopes in the major antigenic site of foot-and-mouth disease virus of serotype C. Journal of General Virology 71:629–637
    [Google Scholar]
  23. Mateu M. G., Andreu D., Carreño C., Roig X., Cairo J.-J., Camarero J. A., Giralt E., Domingo E. 1992; Non-additive effects of multiple amino acid substitutions on antigen-antibody recognition. European Journal of Immunology 22:1385–1389
    [Google Scholar]
  24. Mateu M. G., Hernandez J., Martinez M. A., Feigelstock D., Lea S., Perez J. J., Giralt E., Stuart D., Palma E. L., Domingo E. 1994; Antigenic heterogeneity of a foot-and-mouth disease virus serotype in the field is mediated by very limited sequence variation at several antigenic sites. Journal of Virology 68:1407–1417
    [Google Scholar]
  25. Mateu M. G., Camarero J. A., Andreu D., Giralt E., Domingo E. 1995a; Direct evaluation of the immunodominance of a major antigenic site of foot-and-mouth disease virus in a natural host. Virology 206:298–306
    [Google Scholar]
  26. Mateu M. G., Andreu D., Domingo E. 1995b; Antibodies raised in a natural host and monoclonal antibodies recognize similar antigenic features of foot-and-mouth disease virus. Virology 210:120–127
    [Google Scholar]
  27. Novella I. S., Borrego B., Mateu M. G., Domingo E., Giralt E., Andreu D. 1993; Use of substituted and tandem-repeated peptides to probe the relevance of the highly conserved RGD tripeptide in the immune response against foot-and-mouth disease virus. FEBS Letters 330:253–259
    [Google Scholar]
  28. Parry N. R., Ouldridge E. J., Barnett P. V., Rowlands D. J., Brown F. 1989; Neutralizing epitopes of type O foot-and-mouth disease virus. II. Mapping three conformational sites with synthetic peptide reagents. Journal of General Virology 10:1493–1503
    [Google Scholar]
  29. Pereira H. G. 1981; Foot-and-mouth disease virus. In Virus Diseases of Food Animals vol 2 pp 333–363 Edited by Gibbs E. P. J. New York: Academic Press;
    [Google Scholar]
  30. Pfaff E., Mussgay M., Boehm H. O., Schulz G. E., Schaller H. 1982; Antibodies against a preselected peptide recognize and neutralize foot-and-mouth disease virus. EMBO Journal 1:869–874
    [Google Scholar]
  31. Racaniello V. R. 1990; Cell receptors for picornaviruses. Current Topics in Microbiology and Immunology 161:1–22
    [Google Scholar]
  32. Roivainen M., Huovilainen A., Hovi T. 1990a; Antigenic modification of polioviruses by host proteolytic enzymes. Archives of Virology 111:115–125
    [Google Scholar]
  33. Roivainen M., Montagnon B., Chalumeau H., Murray M., Wimmer E., Hovi T. 1990b; Improved distribution of antigenic site specificity of poliovirus-neutralizing antibodies induced by a protease-cleaved immunogen in mice. Journal of Virology 64:559–562
    [Google Scholar]
  34. Roivainen M., Hyypiä T., Piirainen L., Kalkkinen N., Stanway G., Hovi T. 1991; RGD-dependent entry of coxsackievirus A9 into host cells and its bypass after cleavage of VP1 protein by intestinal proteases. Journal of Virology 65:4735–4740
    [Google Scholar]
  35. Roivainen M., Piirainen L., Hovi T., Virtanen I., Riikonen T., Heino J., Hyypia T. 1994; Entry of coxsackievirus A9 into host cells: specific interactions with αvβ3 integrin, the vitronectin receptor. Virology 203:357–365
    [Google Scholar]
  36. Rowlands D. J., Sangar D. V., Brown F. 1971; Relationship of the antigenic structure of foot-and-mouth disease virus to the process of infection. Journal of General Virology 13:85–93
    [Google Scholar]
  37. Rueckert R. R. 1990; Picornaviruses and their replication. In Virology 2nd edn, pp 507–548 Edited by Fields B. N., Knipe D. M. New York: Raven Press;
    [Google Scholar]
  38. Saiz J. C., Gonzalez M. J., Borca M. V., Sobrino F., Moore D. M. 1991; Identification ofneutralizing antigenic sites on VP 1 and VP2 of type A5 foot-and-mouth disease virus, defined by neutralization-resistant variants. Journal of Virology 65:2518–2524
    [Google Scholar]
  39. Sobrino F., Davila M., Ortin J., Domingo E. 1983; Multiple genetic variants arise in the course of replication of foot-and-mouth disease virus in cell culture. Virology 128:310–318
    [Google Scholar]
  40. Strohmaier K., Franze R., Adam K. H. 1982; Location and characterization of the antigenic portion of the FMDV immunizing protein. Journal of General Virology 59:295–306
    [Google Scholar]
  41. Thomas A. A. M., Woortmeuer R. J., Puuk W., Barteling S. J. 1988; Antigenic sites of foot-and-mouth disease virus type A10. Journal of Virology 62:2782–2789
    [Google Scholar]
  42. Verdaguer N., Mateu M. G., Andreu D., Giralt E., Domingo E., Fita I. 1995; Structure of the major antigenic loop of foot-and- mouth disease virus complexed to anti-virus neutralizing antibody. Direct involvement of Arg-Gly-Asp in the interaction. EMBO Journal 14:1690–1696
    [Google Scholar]
  43. Wild T. F., Brown F. 1967; Nature of the inactivating action of trypsin on foot-and-mouth disease virus. Journal of General Virology 1:247–250
    [Google Scholar]
  44. Wild T. F., Burroughs J. N., Brown F. 1969; Surface structure of foot-and-mouth disease virus. Journal of General Virology 4:313–320
    [Google Scholar]
  45. Xie Q.-C., McCahon D., Crowther J. R., Belsham G. J., McCullough K. C. 1987; Neutralization of foot-and-mouth disease virus can be mediated through any of at least three separate antigenic sites. Journal of General Virology 68:1637–1647
    [Google Scholar]
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