1887

Abstract

Mouse monoclonal antibodies (mAbs) were employed to select neutralization escape mutants of equine rhinitis A virus (ERAV). Amino acid changes in the ERAV mutants resulting in resistance to neutralization were identified in capsid protein VP1 at Lys-114, Pro-240 and Thr-241. Although the changes were located in different parts of the polypeptide chain, these mutants exhibited cross-resistance against all four mAbs employed, indicating that these residues contribute to a single immunogenic site. To explain this result, we constructed a model of the three-dimensional structure of the ERAV capsid based on comparison with the closely related foot-and-mouth disease virus (FMDV O). According to this model, VP1 is folded so that Lys-114 is in the E–F loop of the polypeptide chain at a considerable distance from Pro-240 and Trp-241 in the C-terminal region. However, around the fivefold axis of symmetry, the C terminus of VP1 in each protomer extends to the E–F loop of the adjacent VP1 in the next protomer. We therefore propose that the immunogenic site in ERAV is formed as a result of the close proximity of the Lys-114 residue in the E–F loop of one VP1 molecule and of the Pro-240/Thr-241 residues in the adjacent VP1 polypeptide chain. In terms of the overall architecture of the viral capsid structure, this site in ERAV most closely resembles the immunogenic site 1 of FMDV O.

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2003-09-01
2019-10-15
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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.[CrossRef]
    [Google Scholar]
  2. Boege, U., Kobasa, D., Onodera, S., Parks, G. D., Palmenberg, A. C. & Scraba, D. G. ( 1991; ). Characterization of mengo virus neutralization epitopes. Virology 181, 1–13.[CrossRef]
    [Google Scholar]
  3. Brown, F. & Cartwright, B. ( 1963; ). Purification of radioactive foot-and-mouth disease virus. Nature 199, 1169–1170.
    [Google Scholar]
  4. Ditchfield, J. & MacPherson, L. W. ( 1965; ). The properties and classification of two new rhinoviruses recovered from horses in Toronto. Cornell Vet 55, 425–431.
    [Google Scholar]
  5. Fukunaga, Y., Kumanomido, T., Kamada, M. & Wada, R. ( 1983; ). Equine picornaviruses: isolation of virus from the oral cavity of healthy horses. Bull Equine Res Inst 20, 103–109.
    [Google Scholar]
  6. Hofer, B., Steck, F., Gerber, H., Lohrer, J. & Paccaud, M. F. ( 1973; ). An investigation of the etiology of viral respiratory disease in a remount depot. In Proceedings of the 3rd International Conference on Equine Infectious Diseases, pp. 527–545. Edited by J. T. Bryans & H. Gerber. Basel: Karger.
  7. Holmes, D. F., Kemen, M. J. & Coggins, L. ( 1978; ). Equine rhinovirus infection – serological evidence of infection in selected United States horse populations. In Proceedings of the 4th International Conference on Equine Infectious Diseases, pp. 315–319. Edited by J. T. Bryans & H. Gerber. Princetown: Veterinary Publications.
  8. Jones, T. A., Zou, J. Y., Cowan, S. W. & Kjeldgaard, M. ( 1991; ). Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr 47, 110–119.[CrossRef]
    [Google Scholar]
  9. Kohler, G. & Milstein, C. ( 1975; ). Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256, 495–497.[CrossRef]
    [Google Scholar]
  10. Lea, S., Hernandez, J., Blakemore, W. & 9 other authors ( 1994; ). The structure and antigenicity of a type-C foot-and-mouth disease virus. Structure 2, 123–139.[CrossRef]
    [Google Scholar]
  11. Li, F., Browning, G. F., Studdert, M. J. & Crabb, B. S. ( 1996; ). Equine rhinovirus 1 is more closely related to foot-and-mouth disease virus than to other picornaviruses. Proc Natl Acad Sci U S A 93, 990–995.[CrossRef]
    [Google Scholar]
  12. Li, F., Drummer, H. E., Ficorilli, N., Studdert, M. J. & Crabb, B. S. (1997; ). Identification of noncytopathic equine rhinovirus 1 as a cause of acute febrile respiratory disease in horses. J Clin Microbiol 35, 937–943.
    [Google Scholar]
  13. Logan, D., Abu Ghazaleh, R., Blakemore, W. & 10 other authors ( 1993; ). Structure of a major immunogenic site on foot-and-mouth disease virus. Nature 362, 566–568.[CrossRef]
    [Google Scholar]
  14. Luo, M., Vriend, G., Kamer, G. & 7 other authors ( 1987; ). The atomic structure of mengo virus at 3·0 A resolution. Science 235, 182–191.[CrossRef]
    [Google Scholar]
  15. McCollum, W. H. & Timoney, P. J. ( 1991; ). Studies on the seroprevalence and frequency of equine rhinovirus-1 and -2 infections in normal horse urine. In Proceedings of the 6th International Conference on Equine Infectious Diseases, pp. 83–87. Edited by W. Plowright, P. D. Rossdale & J. F. Wade. Newmarket: R and W Publications.
  16. Mateu, M. G. ( 1995; ). Antibody recognition of picornaviruses and escape from neutralization: a structural view. Virus Res 38, 1–24.[CrossRef]
    [Google Scholar]
  17. Newman, J. F., Rowlands, D. J. & Brown, F. ( 1973; ). A physico-chemical sub-grouping of the mammalian picornaviruses. J Gen Virol 18, 171–180.[CrossRef]
    [Google Scholar]
  18. Newman, J. F., Rowlands, D. J., Brown, F., Goodridge, D., Burrows, R. & Steck, F. ( 1977; ). Physicochemical characterization of two serologically unrelated equine rhinoviruses. Intervirology 8, 145–154.[CrossRef]
    [Google Scholar]
  19. Plummer, G. ( 1962; ). An equine respiratory virus with enterovirus properties. Nature 195, 519–520.[CrossRef]
    [Google Scholar]
  20. Rossmann, M. G., Arnold, E., Erickson, J. W. & 10 other authors ( 1985; ). Structure of a human common cold virus and functional relationship to other picornaviruses. Nature 317, 145–153.[CrossRef]
    [Google Scholar]
  21. Rowlands, D. J. & Brown, F. ( 2002; ). Antigenic variation in foot-and-mouth disease virus. In Molecular Biology of Picornaviruses, pp. 51–58. Edited by B. L. Semler & E. Wimmer. Washington, DC: ASM Press.
  22. Sherry, B., Mosser, A. G., Colonno, J. & Rueckert, R. R. ( 1985; ). Use of monoclonal antibodies to identify four neutralization immunogens on a common cold picornavirus human rhinovirus 14. J Virol 57, 246–257.
    [Google Scholar]
  23. Steck, F., Hofer, B., Schaeren, B., Nicolet, J. & Gerber, H. ( 1978; ). Equine rhinoviruses: new serotypes. In Proceedings of the 4th International Conference on Equine Infectious Diseases, pp. 321–328. Edited by J. T. Bryans & H. Gerber. Princetown: Veterinary Publications.
  24. Studdert, M. J. & Gleeson, L. J. ( 1977; ). Isolation of equine rhinovirus type 1. Aust Vet J 53, 452.
    [Google Scholar]
  25. Studdert, M. J. & Gleeson, L. J. ( 1978; ). Isolation and characterisation of an equine rhinovirus. Zentbl Vetmed Reihe B 25, 225–237.
    [Google Scholar]
  26. Varrasso, A., Drummer, H. E., Huang, J. A., Stevenson, R. A., Ficorilli, N., Studdert, M. J. & Hartley, C. A. ( 2001; ). Sequence conservation and antigenic variation of the structural proteins of equine rhinitis A virus. J Virol 75, 10550–10556.[CrossRef]
    [Google Scholar]
  27. Warner, S., Hartley, C. A., Stevenson, R. A., Ficorilli, N., Varrasso, A., Studdert, M. J. & Crabb, B. S. ( 2001; ). Evidence that equine rhinitis A virus VP1 is a target of neutralizing antibodies and participates directly in receptor binding. J Virol 75, 9274–9281.[CrossRef]
    [Google Scholar]
  28. Wutz, G., Auer, H., Nowotny, N., Grosse, B., Skern, T. & Kuechler, E. ( 1996; ). Equine rhinovirus serotypes 1 and 2: relationship to each other and to aphthoviruses and cardioviruses. J Gen Virol 77, 1719–1730.[CrossRef]
    [Google Scholar]
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