1887

Abstract

Equine arteritis virus (EAV) causes a systemic infection in equids with variable outcome, ranging from subclinical infections to severe disease, and also has the capacity to induce abortion in pregnant mares and persistent infections in stallions. The serum virus-neutralizing antibody response that invariably develops in the infected animal lasts for many months or years and is believed to play an important role in virus clearance. However, very little is known about cellular immunity against EAV because of a lack of methods for evaluating these immune responses. In the present study, we describe methods for detecting cytotoxic T lymphocyte (CTL) precursors in the peripheral blood of EAV-convalescent ponies using a Cr release cytolysis assay. Primary equine dermal cells, used as CTL targets, were shown to express MHC I but not MHC II and to retain Cr efficiently and support EAV replication. Peripheral blood mononuclear cells (PBMC) collected from EAV-convalescent ponies that had been incubated with or without live EAV were used as effectors. EAV-induced PBMC cultures showed evidence of expansion and activation of lymphoblasts, with an increase in the CD8/CD4 ratio in comparison with mock-induced PBMC. The cytotoxicity induced by EAV-stimulated PBMC was virus specific, showed genetic restriction, was mediated by CD8 T lymphocytes and could be detected for periods of 4 months to more than 1 year post-infection. These findings and methods will hopefully contribute to an understanding of virus–host interactions in horses, in particular the mechanisms of virus clearance occurring during EAV infection.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.19144-0
2003-10-01
2019-10-22
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/10/vir842745.html?itemId=/content/journal/jgv/10.1099/vir.0.19144-0&mimeType=html&fmt=ahah

References

  1. 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]
  2. Castillo-Olivares, J., de Vries, A. A., Raamsman, M. J. & 8 other authors ( 2001; ). Evaluation of a prototype sub-unit vaccine against equine arteritis virus comprising the entire ectodomain of the virus large envelope glycoprotein (GL): induction of virus-neutralizing antibody and assessment of protection in ponies. J Gen Virol 82, 2425–2435.
    [Google Scholar]
  3. Chirnside, E. D., de Vries, A. A., Mumford, J. A. & Rottier, P. J. ( 1995; ). Equine arteritis virus-neutralizing antibody in the horse is induced by a determinant on the large envelope glycoprotein GL. J Gen Virol 76, 1989–1998.[CrossRef]
    [Google Scholar]
  4. de Vries, A. A. F., Chirnside, E. D., Horzinek, M. C. & Rottier, P. J. M. ( 1992; ). Structural proteins of equine arteritis virus. J Virol 66, 6294–6303.
    [Google Scholar]
  5. Even, C., Rowland, R. R. & Plagemann, P. G. ( 1995; ). Cytotoxic T cells are elicited during acute infection of mice with lactate dehydrogenase-elevating virus but disappear during the chronic phase of infection. J Virol 69, 5666–5676.
    [Google Scholar]
  6. Flomenberg, P., Piaskowski, V., Truitt, R. L. & Casper, J. T. ( 1996; ). Human adenovirus-specific CD8+ T-cell responses are not inhibited by E3-19K in the presence of gamma interferon. J Virol 70, 6314–6322.
    [Google Scholar]
  7. Fukunaga, Y., Imagawa, H., Tabuchi, E. & Akiyama, Y. ( 1981; ). Clinical and virological findings on experimental equine viral arteritis in horses. Bull Equine Res Inst 18, 110–118.
    [Google Scholar]
  8. Fukunaga, Y., Wada, R., Matsumura, T., Sugiura, T. & Imagawa, H. ( 1990; ). Induction of immune response and protection from equine viral arteritis (EVA) by formalin inactivated-virus vaccine for EVA in horses. J Vet Med Ser B 37, 135–141.[CrossRef]
    [Google Scholar]
  9. Gerber, H., Steck, F., Hofer, B., Walther, L., Friedli, U., Bryans, J. T. & Gerber, H. ( 1978; ). Serological investigations on equine viral arteritis. In Proceedings of the 4th International Conference on Equine Infectious Diseases, Lyon, 1976, pp. 461–465. Edited by J. T. Bryans & H. Gerber. Princeton, NJ: Veterinary Publications, Inc.
  10. Gravell, M., London, W. T., Leon, M., Palmer, A. E. & Hamilton, R. S. ( 1986; ). Elimination of persistent simian hemorrhagic fever (SHF) virus infection in patas monkeys. Proc Soc Exp Biol Med 181, 219–225.[CrossRef]
    [Google Scholar]
  11. Hammond, S. A., Issel, C. J. & Montelaro, R. C. ( 1998; ). General method for the detection and in vitro expansion of equine cytolytic T lymphocytes. J Immunol Methods 213, 73–85.[CrossRef]
    [Google Scholar]
  12. Hannant, D. & Mumford, J. A. ( 1989; ). Cell mediated immune responses in ponies following infection with equine influenza virus (H3N8): the influence of induction culture conditions on the properties of cytotoxic effector cells. Vet Immunol Immunopathol 21, 327–337.[CrossRef]
    [Google Scholar]
  13. Koksoy, S., Phipps, A. J., Hayes, K. A. & Mathes, L. E. ( 2001; ). SV40 immortalization of feline fibroblasts as targets for MHC restricted cytotoxic T-cell assays. Vet Immunol Immunopathol 79, 285–295.[CrossRef]
    [Google Scholar]
  14. Labarque, G. G., Nauwynck, H. J., Van Reeth, K. & Pensaert, M. B. ( 2000; ). Effect of cellular changes and onset of humoral immunity on the replication of porcine reproductive and respiratory syndrome virus in the lungs of pigs. J Gen Virol 81, 1327–1334.
    [Google Scholar]
  15. Lonning, S. M., Zhang, W. & McGuire, T. C. ( 1999; ). Detection and induction of equine infectious anemia virus-specific cytotoxic T-lymphocyte responses by use of recombinant retroviral vectors. J Virol 73, 2762–2769.
    [Google Scholar]
  16. Lopez Fuertes, L., Domenech, N., Alvarez, B., Ezquerra, A., Dominguez, J., Castro, J. M. & Alonso, F. ( 1999; ). Analysis of cellular immune response in pigs recovered from porcine respiratory and reproductive syndrome infection. Virus Res 64, 33–42.[CrossRef]
    [Google Scholar]
  17. Lunn, D. P., Holmes, M. A., Antczak, D. F. & 19 other authors ( 1998; ). Report of the Second Equine Leucocyte Antigen Workshop, Squaw Valley, California, July 1995. Vet Immunol Immunopathol 31, 101–143.
    [Google Scholar]
  18. McCollum, W. H. ( 1969; ). Development of a modified virus strain and vaccine for equine viral arteritis. J Am Vet Med Assoc 155, 318–322.
    [Google Scholar]
  19. McCollum, W. H. ( 1976; ). Studies of passive immunity in foals to equine viral arteritis. Vet Microbiol 1, 45–54.[CrossRef]
    [Google Scholar]
  20. McCollum, W. H. & Timoney, P. J. ( 1998; ). Experimental observations on the virulence of isolates of Equine Arteritis Virus. In Proceedings of the 8th International Conference of Equine Infectious Diseases, pp. 359–362. Edited by U. Wernery, J. F. Wade, J. A. Mumford & O. R. Kaaden. Newmarket: R&W Publications.
  21. McGuire, T. C., Tumas, D. B., Byrne, K. M., Hines, M. T., Leib, S. R., Brassfield, A. L., O'Rourke, K. I. & Perryman, L. E. ( 1994; ). Major histocompatibility complex-restricted CD8+ cytotoxic T lymphocytes from horses with equine infectious anemia virus recognize Env and Gag/PR proteins. J Virol 68, 1459–1467.
    [Google Scholar]
  22. 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.[CrossRef]
    [Google Scholar]
  23. 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]
  24. Neu, S. M., Timoney, P. J. & McCollum, W. H. ( 1987; ). Persistent infection of the reproductive tract in stallions experimentally infected with equine arteritis virus. In Proceedings of the 5th International Conference on Equine Infectious Diseases, pp 149–154. Edited by D. G. Powell. Lexington: University Press of Kentucky.
  25. Ohishi, K., Inui, K., Yamanouchi, K. & Barrett, T. ( 1999; ). Cell-mediated immune responses in cattle vaccinated with a vaccinia virus recombinant expressing the nucleocapsid protein of rinderpest virus. J Gen Virol 80, 1627–1634.
    [Google Scholar]
  26. 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]
  27. Romito, M., Du Plessis, D. H. & Viljoen, G. J. ( 1999; ). Immune responses in a horse inoculated with the VP2 gene of African horsesickness virus. Onderstepoort J Vet Res 66, 139–144.
    [Google Scholar]
  28. Samsom, J. N., de Bruin, T. G., Voermans, J. J., Meulenberg, J. J., Pol, J. M. & Bianchi, A. T. ( 2000; ). Changes of leukocyte phenotype and function in the broncho-alveolar lavage fluid of pigs infected with porcine reproductive and respiratory syndrome virus: a role for CD8+cells. J Gen Virol 81, 497–505.
    [Google Scholar]
  29. Sharpe, S., Beer, B., Hall, G., Dennis, M., Norley, S. & Cranage, M. ( 2001; ). Analysis of SIV-specific CTL in the rhesus macaque model of AIDS: the use of simian fibroblasts as an alternative source of target cells for chromium release assays. J Immunol Methods 258, 137–140.[CrossRef]
    [Google Scholar]
  30. Timoney, P. J. & McCollum, W. H. ( 1988; ). Equine viral arteritis – epidemiology and control. J Equ Vet Sci 8, 54–59.[CrossRef]
    [Google Scholar]
  31. van den Broek, M. F., Sporri, R., Even, C., Plagemann, P. G., Hanseler, E., Hengartner, H. & Zinkernagel, R. M. ( 1997; ). Lactate dehydrogenase-elevating virus (LDV): lifelong coexistence of virus and LDV-specific immunity. J Immunol 159, 1585–1588.
    [Google Scholar]
  32. Zhang, W., Auyong, D. B., Oaks, J. L. & McGuire, T. C. ( 1999; ). Natural variation of equine infectious anemia virus Gag protein cytotoxic T lymphocyte epitopes. Virology 261, 242–252.[CrossRef]
    [Google Scholar]
  33. Zwadlo, G., Bruggen, J., Gerhards, G., Schlegel, R. & Sorg, C. ( 1988; ). Two calcium-binding proteins associated with specific stage myeloid cell differentiation are expressed by subsets of macrophages in inflammatory tissues. Clin Exp Immunol 72, 510–515.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.19144-0
Loading
/content/journal/jgv/10.1099/vir.0.19144-0
Loading

Data & Media loading...

Most Cited This Month

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