1887

Abstract

Equine herpesvirus-1 (EHV-1) causes serious disease in horses throughout the world, despite the frequent use of vaccines. CTLs are thought to be critical for protection from primary and reactivating latent EHV-1 infections. However, the antigen-specificity of EHV-1-specific CTLs is unknown. The aim of this study was to identify EHV-1 genes that encode proteins containing CTL epitopes and to determine their MHC I (or ELA-A in the horse) restriction. Equine dendritic cells, transfected with a series of EHV-1 genes, were used to stimulate autologous CTL precursor populations derived from previously infected horses. Cytotoxicity was subsequently measured against EHV-1-infected PWM lymphoblast targets. Dendritic cells were infected with EHV-1 (positive control) or transfected with plasmids encoding the gB, gC, gD, gE, gH, gI, gL, immediate-early (IE) or early protein of EHV-1 using the PowderJect XR-1 research device. Dendritic cells transfected with the IE gene induced CTL responses in four of six ponies. All four of these ponies shared a common ELA-A3.1 haplotype. Dendritic cells transfected with gC, gD, gI and gL glycoproteins induced CTLs in individual ponies. The cytotoxic activity was ELA-A-restricted, as heterologous targets from ELA-A mismatched ponies were not killed and an MHC I blocking antibody reduced EHV-1-specific killing. This is the first identification of an EHV-1 protein containing ELA-A-restricted CTL epitopes. This assay can now be used to study CTL specificity for EHV-1 proteins in horses with a broad range of ELA-A haplotypes, with the goal of developing a multi-epitope EHV-1 vaccine.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.19268-0
2003-10-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/10/vir842625.html?itemId=/content/journal/jgv/10.1099/vir.0.19268-0&mimeType=html&fmt=ahah

References

  1. Allen G. P., Yeargan M. R. 1987; Use of lambda gt11 and monoclonal antibodies to map the genes for the six major glycoproteins of equine herpesvirus 1. J Virol 61:2454–2461
    [Google Scholar]
  2. Allen G. P., 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. D., Smith K. C. 1999; Advances in understanding of the pathogenesis, epidemiology, and immunological control of equid herpesvirus abortion. In Equine Infectious Diseases VIII Proceedings of the Eighth International Conference. Dubai, 23–26 March, 1998 , 1st edn. pp  129–146 Edited by Wernery U., Wade J. F., Mumford J. A., Kaaden O.-R. Newmarket: R & W Publications;
    [Google Scholar]
  4. Allen T. M., Vogel T. U., Fuller D. H. 11 other authors 2000; Induction of AIDS virus-specific CTL activity in fresh, unstimulated peripheral blood lymphocytes from rhesus macaques vaccinated with a DNA prime/modified vaccinia virus Ankara boost regimen. J Immunol 164:4968–4978
    [Google Scholar]
  5. Antczak D. F. 1992; The major histocompatibility complex of the horse. In Equine Infectious Diseases IV . Proceedings of the Sixth International Conference. Cambridge, 1991 pp  99–112 Edited by Plowright W., Rossdale P. D., Wade J. F. Newmarket: R & W Publications;
    [Google Scholar]
  6. 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]
  7. Audibert F. M., Lise L. D. 1993; Adjuvants: current status, clinical perspectives and future prospects. Trends Pharmacol Sci 14:174–178
    [Google Scholar]
  8. Audonnet J. C., Winslow J., Allen G., Paoletti E. 1990; Equine herpesvirus type 1 unique short fragment encodes glycoproteins with homology to herpes simplex virus type 1 gD, gI and gE. J Gen Virol 71:2969–2978
    [Google Scholar]
  9. Bailey E., Antczak D. F., Bernoco D. 7 other authors 1984; Joint report of the Second International Workshop on Lymphocyte Alloantigens of the Horse, held 3–8 October 1982. Anim Blood Groups Biochem Genet 15:123–132
    [Google Scholar]
  10. Bailey E., Marti E., Fraser D. G., Antczak D. F., Lazary S. 2000; Immunogenetics of the horse. In The Genetics of the Horse pp  123–155 Edited by Bowling A. T., Ruvinsky A. New York: CABI;
    [Google Scholar]
  11. Banchereau J., Steinman R. M. 1998; Dendritic cells and the control of immunity. Nature 392:245–252
    [Google Scholar]
  12. Baxi M. K., Efstathiou S., Lawrence G., Whalley J. M., Slater J. D., Field H. J. 1995; The detection of latency-associated transcripts of equine herpesvirus 1 in ganglionic neurons. J Gen Virol 76:3113–3118
    [Google Scholar]
  13. Bhardwaj N., Bender A., Gonzalez N., Bui L. K., Garrett M. C., Steinman R. M. 1995; Stimulation of human anti-viral CD8+ cytolytic T lymphocytes by dendritic cells. Adv Exp Med Biol 378:375–379
    [Google Scholar]
  14. Birch-Machin I., Ryder S., Taylor L. 11 other authors 2000; Utilisation of bacteriophage display libraries to identify peptide sequences recognised by equine herpesvirus type 1 specific equine sera. J Virol Methods 88:89–104
    [Google Scholar]
  15. Borchers K., Slater J. 1993; A nested PCR for the detection and differentiation of EHV-1 and EHV-4. J Virol Methods 45:331–336
    [Google Scholar]
  16. Bryans J. T., Allen G. P. 1989; Herpesviral diseases of the horse. In Herpesvirus Diseases of Cattle, Horses, and Pigs pp  176–229 Edited by Wittmann G. Boston: Kluwer;
    [Google Scholar]
  17. Burki F., Rossmanith W., Nowotny N., Pallan C., Mostl K., Lussy H. 1990; Viraemia and abortions are not prevented by two commercial equine herpesvirus-1 vaccines after experimental challenge of horses. Vet Q 12:80–86
    [Google Scholar]
  18. Caughman G. B., Lewis J. B., Smith R. H., Harty R. N., O'Callaghan D. J. 1995; Detection and intracellular localization of equine herpesvirus 1 IR1 and IR2 gene products by using monoclonal antibodies. J Virol 69:3024–3032
    [Google Scholar]
  19. Chesters P. M., Allsop R., Purewal A., Edington N. 1997; Detection of latency-associated transcripts of equid herpesvirus 1 in equine leukocytes but not in trigeminal ganglia. J Virol 71:3437–3443
    [Google Scholar]
  20. Cohen J. 1993; Naked DNA points way to vaccines. Science 259:1691–1692
    [Google Scholar]
  21. Crabb B. S., Allen G. P., Studdert M. J. 1991; Characterization of the major glycoproteins of equine herpesviruses 4 and 1 and asinine herpesvirus 3 using monoclonal antibodies. J Gen Virol 72:2075–2082
    [Google Scholar]
  22. Dohmann K., Wagner B., Horohov D. W., Leibold W. 2000; Expression and characterisation of equine interleukin 2 and interleukin 4. Vet Immunol Immunopathol 77:243–256
    [Google Scholar]
  23. 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
    [Google Scholar]
  24. Ellis R. W. 1999; New technologies for making vaccines. In Vaccines , 3rd edn. pp  881–901 Edited by Plotkin S. A., Orenstein W. A. Philadelphia: W. B. Saunders;
    [Google Scholar]
  25. Ellis J. A., Bogdan J. R., Kanara E. W., Morley P. S., Haines D. M. 1995; Cellular and antibody responses to equine herpesviruses 1 and 4 following vaccination of horses with modified-live and inactivated viruses. [see comments]. J Am Vet Med Assoc 206:823–832
    [Google Scholar]
  26. Elton D. M., Bonass W. A., Killington R. A., Meredith D. M., Halliburton I. W. 1991; Location of open reading frames coding for equine herpesvirus type-1 glycoproteins with homology to gE and gI of herpes simplex virus. Am J Vet Res 52:1252–1257
    [Google Scholar]
  27. Flowers C. C., Flowers S. P., Sheng Y., Tarbet E. B., Jennings S. R., O'Callaghan D. J. 1995; Expression of membrane-bound and secreted forms of equine herpesvirus 1 glycoprotein D by recombinant baculovirus. Virus Res 35:17–34
    [Google Scholar]
  28. Foster C. S., Tsai Y., Monroe J. G., Campbell R., Cestari M., Wetzig R., Knipe D., Greene M. I. 1986; Genetic studies on murine susceptibility to herpes simplex keratitis. Clin Immunol Immunopathol 40:313–325
    [Google Scholar]
  29. Fu T. M., Bonneau R. H., Epler M., Tevethia M. J., Alam S., Verner K., Tevethia S. S. 1996; Induction and persistence of a cytotoxic T lymphocyte (CTL) response against a herpes simplex virus-specific CTL epitope expressed in a cellular protein. Virology 222:269–274
    [Google Scholar]
  30. Fu T. M., Guan L., Friedman A., Schofield T. L., Ulmer J. B., Liu M. A., Donnelly J. J. 1999; Dose dependence of CTL precursor frequency induced by a DNA vaccine and correlation with protective immunity against influenza virus challenge. J Immunol 162:4163–4170
    [Google Scholar]
  31. Gallichan W. S., Johnson D. C., Graham F. L., Rosenthal K. L. 1993; Mucosal immunity and protection after intranasal immunization with recombinant adenovirus expressing herpes simplex virus glycoprotein B. J Infect Dis 168:622–629
    [Google Scholar]
  32. Gilkerson J. R., Love D. N., Whalley J. M. 1998; Epidemiology of equine herpesvirus abortion: searching for clues to the future. Aust Vet J 76:675–676
    [Google Scholar]
  33. Goldsby R., Kindt T., Osborne B. 2000; Kuby Immunology . , 4th edn. pp  427–429 New York: W. H. Freeman;
  34. Hammond S. A., Horohov D., Montelaro R. C. 1999; Functional characterization of equine dendritic cells propagated ex vivo using recombinant human GM-CSF and recombinant equine IL-4. Vet Immunol Immunopathol 71:197–214
    [Google Scholar]
  35. Hassett D. E., Whitton J. L. 1996; DNA immunization. Trends Microbiol 8:307–312
    [Google Scholar]
  36. Jones C. M., Cose S. C., Carbone F. R. 1997; Evidence for cooperation between TCR V region and junctional sequences in determining a dominant cytotoxic T lymphocyte response to herpes simplex virus glycoprotein B. Int Immunol 9:1319–1328
    [Google Scholar]
  37. Koen M. T., Walker C., Wellington J. E., Love D. N., Whalley J. M. 2000; Characterisation of IE and UL5 gene products of equine herpesvirus 1 using DNA inoculation of mice. Arch Virol 145:2677–2686
    [Google Scholar]
  38. Krisky D. M., Wolfe D., Goins W. F., Marconi P. C., Ramakrishnan R., Mata M., Rouse R. J., Fink D. J., Glorioso J. C. 1998; Deletion of multiple immediate-early genes from herpes simplex virus reduces cytotoxicity and permits long-term gene expression in neurons. Gene Ther 5:1593–1603
    [Google Scholar]
  39. Kukreja A., Love D. N., Whalley J. M., Field H. J. 1998; Study of the protective immunity of co-expressed glycoprotein H and L of equine herpesvirus-1 in a murine intranasal infection model. Vet Microbiol 60:1–11
    [Google Scholar]
  40. Lekstrom-Himes J. A., Hohman P., Warren T., Wald A., Nam J. M., Simonis T., Corey L., Straus S. E. 1999; Association of major histocompatibility complex determinants with the development of symptomatic and asymptomatic genital herpes simplex virus type 2 infections. J Infect Dis 179:1077–1085
    [Google Scholar]
  41. Ludewig B., Ehl S., Karrer U., Odermatt B., Hengartner H., Zinkernagel R. M. 1998; Dendritic cells efficiently induce protective antiviral immunity. J Virol 72:3812–3818
    [Google Scholar]
  42. Lunn D. P., Holmes M. A., Antczak D. F. 1996; Summary report of the 2nd Equine Leucocyte Antigen Worksop; July 1995; Squaw Valley, California. Vet Immunol Immunopathol 54:159–161
    [Google Scholar]
  43. Lunn D. P., Soboll G., Schram B. R. 7 other authors 1999; Antibody responses to DNA vaccination of horses using the influenza virus hemagglutinin gene. Vaccine 17:2245–2258
    [Google Scholar]
  44. McGuire T. C., Zhang W., Hines M. T., Henney P. J., Byrne K. M. 1997; Frequency of memory cytotoxic T lymphocytes to equine infectious anemia virus proteins in blood from carrier horses. Virology 238:85–93
    [Google Scholar]
  45. McGuire T. C., Leib S. R., Lonning S. M., Zhang W., Byrne K. M., Mealey R. H. 2000; Equine infectious anaemia virus proteins with epitopes most frequently recognized by cytotoxic T lymphocytes from infected horses. J Gen Virol 81:2735–2739
    [Google Scholar]
  46. Manickan E., Kanangat S., Rouse R. J., Yu Z., Rouse B. T. 1997; Enhancement of immune response to naked DNA vaccine by immunization with transfected dendritic cells. J Leukoc Biol 61:125–132
    [Google Scholar]
  47. Munro K. I., Wellington J. E., Love D. N., Whalley J. M. 1999; Characteristics of glycoprotein B of equine herpesvirus 1 expressed by a recombinant baculovirus. Vet Microbiol 68:49–57
    [Google Scholar]
  48. Murali-Krishna K., Altman J. D., Suresh M., Sourdive D., Zajac A., Ahmed R. 1998; In vivo dynamics of anti-viral CD8 T cell responses to different epitopes. An evaluation of bystander activation in primary and secondary responses to viral infection. Adv Exp Med Biol 452:123–142
    [Google Scholar]
  49. Nugent C. T., McNally J. M., Chervenak R., Wolcott R. M., Jennings S. R. 1995; Differences in the recognition of CTL epitopes during primary and secondary responses to herpes simplex virus infection in vivo. Cell Immunol 165:55–64
    [Google Scholar]
  50. O'Brien M. A., Holmes M. A., Lunn D. P., Duffus W. P. H. 1991; Evidence for MHC class-I restricted cytotoxicity in the one-way, primary mixed lymphocyte reaction. Equine Vet J Suppl 12:30–35
    [Google Scholar]
  51. Oehen S., Hengartner H., Zinkernagel R. M. 1991; Vaccination for disease. Science 251:195–198
    [Google Scholar]
  52. 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
    [Google Scholar]
  53. Osterrieder N., Wagner R., Brandmuller C., Schmidt P., Wolf H., Kaaden O. R. 1995; Protection against EHV-1 challenge infection in the murine model after vaccination with various formulations of recombinant glycoprotein gp14 (gB). Virology 208:500–510
    [Google Scholar]
  54. Pedersen L. G., Castelruiz Y., Jacobsen S., Aasted B. 2002; Identification of monoclonal antibodies that cross-react with cytokines from different animal species. Vet Immunol Immunopathol 88:111–122
    [Google Scholar]
  55. Ramsay A. J., Kent S. J., Strugnell R. A., Suhrbier A., Thomson S. A., Ramshaw I. A. 1999; Genetic vaccination strategies for enhanced cellular, humoral and mucosal immunity. Immunol Rev 171:27–44
    [Google Scholar]
  56. Ridgely S. L., McGuire T. C. 2002; Lipopeptide stimulation of MHC class I-restricted memory cytotoxic T lymphocytes from equine infectious anemia virus-infected horses. Vaccine 20:1809–1819
    [Google Scholar]
  57. Rouse R. J., Nair S. K., Lydy S. L., Bowen J. C., Rouse B. T. 1994; Induction in vitro of primary cytotoxic T-lymphocyte responses with DNA encoding herpes simplex virus proteins. J Virol 68:5685–5689
    [Google Scholar]
  58. Ruitenberg K. M., Walker C., Wellington J. E., Love D. N., Whalley J. M. 1999a; DNA-mediated immunization with glycoprotein D of equine herpesvirus 1 (EHV-1) in a murine model of EHV-1 respiratory infection. Vaccine 17:237–244
    [Google Scholar]
  59. Ruitenberg K. M., Walker C., Wellington J. E., Love D. N., Whalley J. M. 1999b; Potential of DNA-mediated vaccination for equine herpesvirus 1. Vet Microbiol 68:35–48
    [Google Scholar]
  60. Ruitenberg K. M., Love D. N., Gilkerson J. R., Wellington J. E., Whalley J. M. 2000a; Equine herpesvirus 1 (EHV-1) glycoprotein D DNA inoculation in horses with pre-existing EHV-1/EHV-4 antibody. Vet Microbiol 76:117–127
    [Google Scholar]
  61. Ruitenberg K. M., Walker C., Love D. N., Wellington J. E., Whalley J. M. 2000b; A prime-boost immunization strategy with DNA and recombinant baculovirus-expressed protein enhances protective immunogenicity of glycoprotein D of equine herpesvirus 1 in naive and infection-primed mice. Vaccine 18:1367–1373
    [Google Scholar]
  62. Siedek E. M., Whelan M., Edington N., Hamblin A. 1999; Equine herpesvirus type 1 infects dendritic cells in vitro: stimulation of T lymphocyte proliferation and cytotoxicity by infected dendritic cells. Vet Immunol Immunopathol 67:17–32
    [Google Scholar]
  63. Simmons A. 1989; H-2-linked genes influence the severity of herpes simplex virus infection of the peripheral nervous system. J Exp Med 169:1503–1507
    [Google Scholar]
  64. Smith R. H., Holden V. R., O'Callaghan D. J. 1995; Nuclear localization and transcriptional activation activities of truncated versions of the immediate-early gene product of equine herpesvirus 1. J Virol 69:3857–3862
    [Google Scholar]
  65. Smith P. M., Zhang Y., Jennings S. R., O'Callaghan D. J. 1998; Characterization of the cytolytic T-lymphocyte response to a candidate vaccine strain of equine herpesvirus 1 in CBA mice. J Virol 72:5366–5372
    [Google Scholar]
  66. Soboll G., Nelson K. M., Leuthner E. S., Clark R. J., Drape R., Macklin M., Swain W. F., Lunn D. P. 2003; Mucosal co-administration of cholera toxin and influenza virus hemagglutinin DNA in ponies generates a local IgA response. Vaccine 21:3081–3092
    [Google Scholar]
  67. Sohn S., Lee E. S., Lee S. 2001; The correlation of MHC haplotype and development of Behcet's disease-like symptoms induced by herpes simplex virus in several inbred mouse strains. J Dermatol Sci 26:173–181
    [Google Scholar]
  68. Steinbach F., Borchers K., Ricciardi-Castagnoli P., Ludwig H., Stingl G., Elbe-Burger A. 1998; Dendritic cells presenting equine herpesvirus-1 antigens induce protective anti-viral immunity. J Gen Virol 79:3005–3014
    [Google Scholar]
  69. Stokes A., Alber D. G., Cameron R. S., Marshall R. N., Allen G. P., Killington R. A. 1996; The production of a truncated form of baculovirus expressed EHV-1 glycoprotein C and its role in protection of C3H (H-2Kk) mice against virus challenge. Virus Res 44:97–109
    [Google Scholar]
  70. Tewari D., Whalley J. M., Love D. N., Field H. J. 1994; Characterization of immune responses to baculovirus-expressed equine herpesvirus type 1 glycoproteins D and H in a murine model. J Gen Virol 75:1735–1741
    [Google Scholar]
  71. Walker C., Ruitenberg K., Wellington J., Whalley J. M., Love D. N. 1997; Genetic immunization with equine herpesvirus-1 glycoprotein D. First International Veterinary Vaccines and Diagnostics Conference. Madison, Wisconsin. July 1997p– 93
    [Google Scholar]
  72. Wellington J. E., Lawrence G. L., Love D. N., Whalley J. M. 1996a; Expression and characterization of equine herpesvirus 1 glycoprotein D in mammalian cell lines. Arch Virol 141:1785–1793
    [Google Scholar]
  73. Wellington J. E., Love D. N., Whalley J. M. 1996b; Evidence for involvement of equine herpesvirus 1 glycoprotein B in cell–cell fusion. Arch Virol 141:167–175
    [Google Scholar]
  74. Whalley J. M., Love D. N., Tewari D., Field H. J. 1995; Characteristics of equine herpesvirus 1 glycoproteins expressed in insect cells. Vet Microbiol 46:193–201
    [Google Scholar]
  75. Zhang W., Lonning S. M., McGuire T. C. 1998; Gag protein epitopes recognized by ELA-A-restricted cytotoxic T lymphocytes from horses with long-term equine infectious anemia virus infection. J Virol 72:9612–9620
    [Google Scholar]
  76. Zhao Y., Holden V. R., Smith R. H., O'Callaghan D. J. 1995; Regulatory function of the equine herpesvirus 1 ICP27 gene product. J Virol 69:2786–2793
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.19268-0
Loading
/content/journal/jgv/10.1099/vir.0.19268-0
Loading

Data & Media loading...

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