1887

Abstract

Equine herpesvirus 1 (EHV-1) causes respiratory and neurological disease and abortion in horses. Animals with high frequencies of cytotoxic T lymphocytes (CTL) show reduced severity of respiratory disease and frequency of abortion, probably by CTL-mediated control of cell-associated viraemia. This study aimed to identify CTL epitopes restricted by selected major histocompatibility complex (MHC) class I alleles expressed in the equine leukocyte antigen (ELA) A3 haplotype. Effector CTL were induced from EHV-1-primed ponies and thoroughbreds with characterized MHC class I haplotypes and screened against P815 target cells transfected with selected EHV-1 genes and MHC class I genes. Targets that expressed EHV-1 gene 64 and the MHC B2 gene were lysed by effector CTL in a genetically restricted manner. There was no T-cell recognition of targets expressing either the MHC B2 gene and EHV-1 genes 2, 12, 14, 16, 35, 63 or 69, or the MHC C1 gene and EHV-1 genes 12, 14, 16 or 64. A vaccinia virus vector encoding gene 64 (NYVAC-64) was also investigated. Using lymphocytes from ELA-A3 horses, the recombinant NYVAC-64 virus induced effector CTL that lysed EHV-1-infected target cells; the recombinant virus also supplied a functional peptide that was expressed by target cells and recognized in an MHC-restricted fashion by CTL induced with EHV-1. This construct may therefore be used to determine the antigenicity of EHV-1 gene 64 for other MHC haplotypes. These techniques are broadly applicable to the identification of additional CTL target proteins and their presenting MHC alleles, not only for EHV-1, but for other equine viruses.

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2006-09-01
2019-11-13
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References

  1. Allen, G. P. ( 2002; ). Respiratory infections by equine herpesvirus types 1 and 4. In Equine Infectious Diseases. Edited by P. Leukeux. Ithaca, NY: International Veterinary Information Service.
  2. Allen, G., Yeargan, M., Costa, L. R. & Cross, R. ( 1995; ). Major histocompatibility complex class I-restricted cytotoxic T-lymphocyte responses in horses infected with equine herpesvirus 1. J Virol 69, 606–612.
    [Google Scholar]
  3. Allen, G. P., Kydd, J. H., Slater, J. & Smith, K. C. ( 1999; ). Advances in understanding of the pathogenesis, epidemiology and immunological control of equine herpesvirus abortion. In Equine Infectious Diseases, vol. VIII, pp. 129–146. Cambridge, UK: R&W Publications (Newmarket) Ltd.
  4. Ambagala, A. P. N., Gopinath, R. S. & Srikumaran, S. ( 2004; ). Peptide transport activity of the transporter associated with antigen processing (TAP) is inhibited by an early protein of equine herpesvirus-1. J Gen Virol 85, 349–353.[CrossRef]
    [Google Scholar]
  5. Antczak, D. F. ( 1992; ). The major histocompatibility complex of the horse. In Equine Infectious Diseases, vol. VI. Cambridge, UK: R&W Publications (Newmarket) Ltd.
  6. Antczak, D. F., Bright, S. M., Remick, L. H. & Bauman, B. E. ( 1982; ). Lymphocyte alloantigens of the horse. I. Serologic and genetic studies. Tissue Antigens 20, 172–187.
    [Google Scholar]
  7. Antczak, D. F., Bailey, E., Barger, B. & 7 other authors ( 1986; ). Joint report of the Third International Workshop on Lymphocyte Alloantigens of the Horse, Kennett Square, Pennsylvania, 25–27 April 1984. Anim Genet 17, 363–373.
    [Google Scholar]
  8. Bailey, E., Marti, E., Fraxer, D. G., Antczak, D. F. & Lazary, S. ( 2000; ). Immunogenetics of the horse. In The Genetics of the Horse, pp. 123–155. Edited by A. T. Bowling & A. Ruvinsky. Wallingford, UK: CABI Publishing.
  9. Bodo, G., Marti, E., Gaillard, C., Weiss, M., Bruckner, L., Gerber, H. & Lazary, S. ( 1994; ). Association of the immune response with the major histocompatibility complex in the horse. In Equine Infectious Diseases, vol, VII, pp. 143–151. Edited by H. Nakajima & W. Plowright. Newmarket, UK: R&W Publications (Newmarket) Ltd.
  10. Charan, S., Palmer, K., Chester, P., Mire-Sluis, A. R., Meager, A. & Edington, N. ( 1997; ). Transforming growth factor-beta induced by live or ultraviolet-inactivated equid herpes virus type-1 mediates immunosuppression in the horse. Immunology 90, 586–591.[CrossRef]
    [Google Scholar]
  11. Chung, C., Leib, S. R., Fraser, D. G., Ellis, S. A. & McGuire, T. C. ( 2003; ). Novel classical MHC class I alleles identified in horses by sequencing clones of reverse transcription-PCR products. Eur J Immunogenet 30, 387–396.[CrossRef]
    [Google Scholar]
  12. Edington, N., Welch, H. M. & Griffiths, L. ( 1994; ). The prevalence of latent equid herpesviruses in the tissues of 40 abattoir horses. Equine Vet J 26, 140–142.[CrossRef]
    [Google Scholar]
  13. Ellis, S. A., Martin, A. J., Holmes, E. C. & Morrison, W. I. ( 1995; ). At least four MHC class I genes are transcribed in the horse: phylogenetic analysis suggests an unusual evolutionary history for the MHC in this species. Eur J Immunogenet 22, 249–260.[CrossRef]
    [Google Scholar]
  14. Grundy, F. J., Baumann, R. P. & O'Callaghan, D. J. ( 1989; ). DNA sequence and comparative analyses of the equine herpesvirus type 1 immediate early gene. Virology 172, 223–236.[CrossRef]
    [Google Scholar]
  15. Gustafson, A. L., Tallmadge, R. L., Ramlachan, N., Miller, D., Bird, H., Antczak, D. F., Raudsepp, T., Chowdhary, B. P. & Skow, L. C. ( 2003; ). An ordered BAC contig map of the equine major histocompatibility complex. Cytogenet Genome Res 102, 189–195.[CrossRef]
    [Google Scholar]
  16. Hannant, D., Jessett, D., O'Neill, T., Dolby, C. A., Cook, R. F. & Mumford, J. A. ( 1993; ). Responses of ponies to equid herpesvirus-1 ISCOM vaccination and challenge with virus to the homologous strain. Res Vet Sci 54, 299–305.[CrossRef]
    [Google Scholar]
  17. Hannant, D., O'Neill, T., Ostlund, E. N., Kydd, J. H., Hopkin, P. J. & Mumford, J. A. ( 1999; ). Equid herpesvirus-induced immunosuppression is associated with lymphoid cells and not soluble circulating factors. Viral Immunol 12, 313–321.[CrossRef]
    [Google Scholar]
  18. Heldens, J. G. M., Hannant, D., Cullinane, A. A., Prendergast, M. J., Mumford, J. A., Nelly, M., Kydd, J. H., Weststrate, M. W. & van den Hoven, R. ( 2001; ). Clinical and virological evaluation of the efficacy of an inactivated EHV1 and EHV4 whole virus vaccine (Duvaxyn EHV1,4). Vaccination/challenge experiments in foals and pregnant mares. Vaccine 19, 4307–4317.[CrossRef]
    [Google Scholar]
  19. Huemer, H. P., Nowotny, N., Crabb, B. S., Meyer, H. & Hubert, P. H. ( 1995; ). gp13(EHV-gC): a complement receptor induced by equine herpesviruses. Virus Res 37, 113–126.[CrossRef]
    [Google Scholar]
  20. Klenerman, P., Cerundolo, V. & Dunbar, P. R. ( 2002; ). Tracking T cells with tetramers: new tales from new tools. Nat Rev Immunol 2, 263–272.[CrossRef]
    [Google Scholar]
  21. Kydd, J. H., Wattrang, E. & Hannant, D. ( 2003; ). Pre-infection frequencies of equine herpesvirus-1 specific, cytotoxic T lymphocytes correlate with protection against abortion following experimental infection of pregnant mares. Vet Immunol Immunopathol 96, 207–217.[CrossRef]
    [Google Scholar]
  22. Mealey, R. H., Sharif, A., Ellis, S. A., Littke, M. H., Leib, S. R. & McGuire, T. C. ( 2005; ). Early detection of dominant Env-specific and subdominant Gag-specific CD8+ lymphocytes in equine infectious anemia virus-infected horses using major histocompatibility complex class I/peptide tetrameric complexes. Virology 339, 110–126.[CrossRef]
    [Google Scholar]
  23. Minke, J. M., Audonnet, J. C. & Fischer, L. ( 2004; ). Equine viral vaccines: the past, present and future. Vet Res 35, 425–443.[CrossRef]
    [Google Scholar]
  24. Mumford, J. A. ( 1994; ). Abortigenic and neurological disease caused by experimental infection with equid herpesvirus-1. In Equine Infectious Diseases, vol. VII, pp. 261–276. Edited by H. Nakajima & W. Plowright. Cambridge, UK: R&W Publications (Newmarket) Ltd.
  25. O'Neill, T., Kydd, J. H., Allen, G. P., Wattrang, E., Mumford, J. A. & Hannant, D. ( 1999; ). Determination of equid herpesvirus 1-specific, CD8+, cytotoxic T lymphocyte precursor frequencies in ponies. Vet Immunol Immunopathol 70, 43–54.[CrossRef]
    [Google Scholar]
  26. Paillot, R., Daly, J. M., Juillard, V., Minke, J. M., Hannant, D. & Kydd, J. H. ( 2005; ). Equine interferon gamma synthesis in lymphocytes after in vivo infection and in vitro stimulation with EHV-1. Vaccine 23, 4541–4551.[CrossRef]
    [Google Scholar]
  27. Paillot, R., Ellis, S. A., Daly, J. M., Audonnet, J. C., Minke, J. M., Davis-Poynter, N., Hannant, D. & Kydd, J. H. ( 2006; ). Characterisation of CTL and IFNγ synthesis in ponies following vaccination with a NYVAC-based construct coding for EHV-1 immediate early gene, followed by challenge infection. Vaccine 24, 1490–1500.[CrossRef]
    [Google Scholar]
  28. Patel, J. R. & Heldens, J. ( 2005; ). Equine herpesviruses 1 (EHV-1) and 4 (EHV-4) – epidemiology, disease and immunoprophylaxis: a brief review. Vet J 170, 14–23.[CrossRef]
    [Google Scholar]
  29. Piccini, A., Perkus, M. E. & Paoletti, E. ( 1987; ). Vaccinia virus as an expression vector. Methods Enzymol 153, 545–563.
    [Google Scholar]
  30. Rappocciolo, G., Birch, J. & Ellis, S. A. ( 2003; ). Down-regulation of MHC class I expression by equine herpesvirus-1. J Gen Virol 84, 293–300.[CrossRef]
    [Google Scholar]
  31. Sinclair, R., Cook, R. F. & Mumford, J. A. ( 1989; ). The characterization of neutralizing and non-neutralizing monoclonal antibodies against equid herpesvirus type 1. J Gen Virol 70, 455–459.[CrossRef]
    [Google Scholar]
  32. Slater, J. D., Borchers, K., Thackray, A. M. & Field, H. J. ( 1994; ). The trigeminal ganglion is a location for equine herpesvirus 1 latency and reactivation in the horse. J Gen Virol 75, 2007–2016.[CrossRef]
    [Google Scholar]
  33. Soboll, G., Whalley, J. M., Koen, M. T., Allen, G. P., Fraser, D. G., Macklin, M. D., Swain, W. F. & Lunn, D. P. ( 2003; ). Identification of equine herpesvirus-1 antigens recognized by cytotoxic T lymphocytes. J Gen Virol 84, 2625–2634.[CrossRef]
    [Google Scholar]
  34. Tallmadge, R. L., Lear, T. & Antczak, D. F. ( 2005; ). Genomic characterization of MHC class I genes of the horse. Immunogenetics 57, 763–774.[CrossRef]
    [Google Scholar]
  35. Tartaglia, J., Perkus, M. E., Taylor, J. & 9 other authors ( 1992; ). NYVAC: a highly attenuated strain of vaccinia virus. Virology 188, 217–232.[CrossRef]
    [Google Scholar]
  36. Telford, E. A., Watson, M. S., McBride, K. & Davison, A. J. ( 1992; ). The DNA sequence of equine herpesvirus-1. Virology 189, 304–316.[CrossRef]
    [Google Scholar]
  37. Thomson, G. R., Mumford, J. A., Campbell, J., Griffiths, L. & Clapham, P. ( 1976; ). Serological detection of equid herpesvirus 1 infections of the respiratory tract. Equine Vet J 8, 58–65.[CrossRef]
    [Google Scholar]
  38. Welch, H. M., Bridges, C. G., Lyon, A. M., Griffiths, L. & Edington, N. ( 1992; ). Latent equid herpesviruses 1 and 4: detection and distinction using the polymerase chain reaction and co-cultivation from lymphoid tissues. J Gen Virol 73, 261–268.[CrossRef]
    [Google Scholar]
  39. Zhang, Y., Smith, P. M., Tarbet, E. B., Osterrieder, N., Jennings, S. R. & O'Callaghan, D. J. ( 1998; ). Protective immunity against equine herpesvirus type-1 (EHV-1) infection in mice induced by recombinant EHV-1 gD. Virus Res 56, 11–24.[CrossRef]
    [Google Scholar]
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