1887

Abstract

The mechanisms responsible for lymphocyte apoptosis in bovine viral diarrhoea have not yet been clarified. Previous work suggests that bovine viral diarrhea virus (BVDV) is only directly responsible for the destruction of a small number of lymphocytes. The aim of this study was to clarify, , the role of macrophages in lymphocyte destruction through indirect mechanisms linked to the biosynthetic activation of these immunocompetent cells on ileal Peyer's patches, as well as the distribution and quantification of apoptosis. Eight colostrum-deprived calves were inoculated intranasally with a non-cytopathic strain of BVDV genotype 1 and killed in batches of two at 3, 6, 9 and 14 days post-inoculation (p.i.). The progressive depletion of Peyer's patches was found to be due to massive lymphocyte apoptosis, with an increase in cleaved caspase-3 and TUNEL-positive cells. Lymphoid depletion was accompanied, from 3 days p.i., by a significant rise in macrophage numbers both in lymphoid follicles and in interfollicular areas. Some macrophages showed signs of viral infection, together with subcellular changes indicative of phagocyte activation and, in some cases, of secretory activity. However, the number of macrophages that showed positive immunostaining for tumour necrosis factor- and interleukin-1, cytokines with a proven ability to induce apoptosis, remained low throughout the experiment in lymphoid follicles, where most apoptotic cells were found. These results thus appear to rule out a major involvement of macrophages and macrophage-secreted chemical mediators in the apoptosis of follicular B lymphocytes during BVDV infection.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.012021-0
2009-11-01
2019-11-21
Loading full text...

Full text loading...

/deliver/fulltext/jgv/90/11/2650.html?itemId=/content/journal/jgv/10.1099/vir.0.012021-0&mimeType=html&fmt=ahah

References

  1. Adler, B., Adler, H., Pfister, H., Jungi, T. W. & Peterhans, E. ( 1997; ). Macrophages infected with cytopathic bovine viral diarrhea virus release a factor(s) capable of priming uninfected macrophages for activation-induced apoptosis. J Virol 71, 3255–3258.
    [Google Scholar]
  2. Archambault, D., Beliveau, C., Couture, Y. & Carman, S. ( 2000; ). Clinical response and immunomodulation following experimental challenge of calves with type 2 noncytopathogenic bovine viral diarrhea virus. Vet Res 31, 215–227.[CrossRef]
    [Google Scholar]
  3. Baigent, S. J., Zhang, G., Fray, M. D., Flick-Smith, H., Goodbourn, S. & McCauley, J. W. ( 2002; ). Inhibition of beta interferon transcription by noncytopathogenic bovine viral diarrhea virus is through an interferon regulatory factor 3-dependent mechanism. J Virol 76, 8979–8988.[CrossRef]
    [Google Scholar]
  4. Bielefeldt Ohmann, H. & Babiuk, L. A. ( 1988; ). Influence of interferons alpha I1 and gamma and of tumour necrosis factor on persistent infection with bovine viral diarrhoea virus in vitro. J Gen Virol 69, 1399–1403.[CrossRef]
    [Google Scholar]
  5. Bendfeldt, S., Grummer, B. & Greiser-Wilke, I. ( 2003; ). No caspase activation but overexpression of Bcl-2 in bovine cells infected with noncytopathic bovine virus diarrhoea virus. Vet Microbiol 96, 313–326.[CrossRef]
    [Google Scholar]
  6. Bendfeldt, S., Ridpath, J. F. & Neill, J. D. ( 2007; ). Activation of cell signaling pathways is dependant on the biotype of bovine viral diarrhea viruses type 2. Virus Res 126, 96–105.[CrossRef]
    [Google Scholar]
  7. Brock, K. V. ( 2003; ). The persistence of bovine viral diarrhea virus. Biologicals 31, 133–135.[CrossRef]
    [Google Scholar]
  8. Clem, R. J. & Miller, L. K. ( 1994; ). Control of programmed cell death by the baculovirus genes p35 and iap. Mol Cell Biol 14, 5212–5222.
    [Google Scholar]
  9. Dukers, D. F., Oudejans, J. J., Vos, W., ten Berge, R. L. & Meijer, C. J. ( 2002; ). Apoptosis in B-cell lymphomas and reactive lymphoid tissues always involves activation of caspase 3 as determined by a new in situ detection method. J Pathol 196, 307–315.[CrossRef]
    [Google Scholar]
  10. Ellis, J. A., West, K. H., Cortese, V. S., Myers, S. L., Carman, S., Martin, K. M. & Haines, D. M. ( 1998; ). Lesions and distribution of viral antigen following an experimental infection of young seronegative calves with virulent bovine virus diarrhea virus-type II. Can J Vet Res 62, 161–169.
    [Google Scholar]
  11. Fauquet, C. M., Mayo, M. A. & Maniloff, J. ( 2005; ). Classification and nomenclature of viruses. In Virus Taxonomy, Eighth Report of the International Committee on Taxonomy of Viruses, pp. 135–143, 981–998. Edited by C. M. Fauquet, M. A. Mayo, J. Maniloff, U. Desselberger & L. A. Ball. San Diego: Elsevier Academic Press.
  12. Fulton, R. W., Ridpath, J. F., Confer, A. W., Saliki, J. T., Burge, L. J. & Payton, M. E. ( 2003; ). Bovine viral diarrhoea virus antigenic diversity: impact on disease and vaccination programmes. Biologicals 31, 89–95.[CrossRef]
    [Google Scholar]
  13. Gómez del Moral, M., Ortuño, E., Fernández-Zapatero, P., Alonso, F., Alonso, C., Ezquerra, A. & Domínguez, J. ( 1999; ). African swine fever virus infection induces tumor necrosis factor alpha production: implications in pathogenesis. J Virol 73, 2173–2180.
    [Google Scholar]
  14. Gómez-Villamandos, J. C., Ruiz-Villamor, E., Bautista, M. J., Sánchez, C. P., Sánchez-Cordón, P. J., Salguero, F. J. & Jover, A. ( 2001; ). Morphological and immunohistochemical changes in splenic macrophages of pigs infected with classical swine fever. J Comp Pathol 125, 98–109.[CrossRef]
    [Google Scholar]
  15. Grummer, B., Moenning, V. & Greiser-Wilke, I. ( 1998; ). Cytopathogenic bovine viral diarrhea viruses induce apoptosis in bovine cell cultures. Dtsch Tierarztl Wochenschr 105, 29–31.
    [Google Scholar]
  16. Grummer, B., Bendfeldt, S. & Greiser-Wilke, I. ( 2002a; ). Apoptosis inhibitors delay the cytopathic effect of bovine viral diarrhoea virus (BVDV). J Vet Med B Infect Dis Vet Public Health 49, 298–303.[CrossRef]
    [Google Scholar]
  17. Grummer, B., Bendfeldt, S., Wagner, B. & Greiser-Wilke, I. ( 2002b; ). Induction of the intrinsic apoptotic pathway in cells infected with cytopathic bovine virus diarrhoea virus. Virus Res 90, 143–153.[CrossRef]
    [Google Scholar]
  18. Hengartner, M. O. ( 2000; ). The biochemistry of apoptosis. Nature 407, 770–776.[CrossRef]
    [Google Scholar]
  19. Huppertz, B., Frank, H. G. & Kaufmann, P. ( 1999; ). The apoptosis cascade – morphological and immunohistochemical methods for its visualization. Anat Embryol (Berl) 200, 1–18.[CrossRef]
    [Google Scholar]
  20. Jensen, J. & Schultz, R. D. ( 1991; ). Effect of infection by bovine viral diarrhea virus (BVDV) in vitro on interleukin-1 activity of bovine monocytes. Vet Immunol Immunopathol 29, 251–265.[CrossRef]
    [Google Scholar]
  21. Kelling, C. L., Steffen, D. J., Topliff, C. L., Eskridge, K. M., Donis, R. O. & Higuchi, D. S. ( 2002; ). Comparative virulence of isolates of bovine viral diarrhea virus type II in experimentally inoculated six- to nine-month-old calves. Am J Vet Res 63, 1379–1384.[CrossRef]
    [Google Scholar]
  22. Kerr, J. F., Wyllie, A. H. & Currie, A. R. ( 1972; ). Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26, 239–257.[CrossRef]
    [Google Scholar]
  23. Labat-Moleur, F., Guillermet, C., Lorimier, P., Robert, C., Lantuejoul, S., Brambilla, E. & Negoescu, A. ( 1998; ). TUNEL apoptotic cell detection in tissue sections: critical evaluation and improvement. J Histochem Cytochem 46, 327–334.[CrossRef]
    [Google Scholar]
  24. Lambot, M., Hanon, E., Lecomte, C., Hamers, C., Letesson, J. J. & Pastoret, P. P. ( 1998; ). Bovine viral diarrhoea virus induces apoptosis in blood mononuclear cells by a mechanism largely dependent on monocytes. J Gen Virol 79, 1745–1749.
    [Google Scholar]
  25. Le, J. & Vilcek, J. ( 1987; ). Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest 56, 234–248.
    [Google Scholar]
  26. Liebler-Tenorio, E. M., Ridpath, J. E. & Neill, J. D. ( 2002; ). Distribution of viral antigen and development of lesions after experimental infection with highly virulent bovine viral diarrhea virus type 2 in calves. Am J Vet Res 63, 1575–1584.[CrossRef]
    [Google Scholar]
  27. Liebler-Tenorio, E. M., Ridpath, J. F. & Neill, J. D. ( 2003a; ). Distribution of viral antigen and development of lesions after experimental infection of calves with a BVDV 2 strain of low virulence. J Vet Diagn Invest 15, 221–232.[CrossRef]
    [Google Scholar]
  28. Liebler-Tenorio, E. M., Ridpath, J. F. & Neill, J. D. ( 2003b; ). Lesions and tissue distribution of viral antigen in severe acute versus subclinical acute infection with BVDV2. Biologicals 31, 119–122.[CrossRef]
    [Google Scholar]
  29. Liebler-Tenorio, E. M., Ridpath, J. E. & Neill, J. D. ( 2004; ). Distribution of viral antigen and tissue lesions in persistent and acute infection with the homologous strain of noncytopathic bovine viral diarrhea virus. J Vet Diagn Invest 16, 388–396.[CrossRef]
    [Google Scholar]
  30. Marshall, D. J., Moxley, R. A. & Kelling, C. L. ( 1996; ). Distribution of virus and viral antigen in specific pathogen-free calves following inoculation with noncytopathic bovine viral diarrhea virus. Vet Pathol 33, 311–318.[CrossRef]
    [Google Scholar]
  31. Noteborn, M. H., Todd, D., Verschueren, C. A., de Gauw, H. W., Curran, W. L., Veldkamp, S., Douglas, A. J., McNulty, M. S., van der EB, A. J. & Koch, G. ( 1994; ). A single chicken anemia virus protein induces apoptosis. J Virol 68, 346–351.
    [Google Scholar]
  32. Odeón, A. C., Kelling, C. L., Marshall, D. J., Estela, E. S., Dubovi, E. J. & Donis, R. O. ( 1999; ). Experimental infection of calves with bovine viral diarrhea virus genotype II (NY-93). J Vet Diagn Invest 11, 221–228.[CrossRef]
    [Google Scholar]
  33. Pedrera, M., Sánchez-Cordón, P. J., Romero-Trevejo, J. L., Risalde, M. A., Greiser-Wilke, I., Núñez, A. & Gómez-Villamandos, J. C. ( 2009; ). Morphological changes and viral distribution in the ileum of colostrum-deprived calves inoculated with noncytopathic bovine viral diarrhea virus genotype-1. J Comp Pathol 141, 52–62.[CrossRef]
    [Google Scholar]
  34. Rathmell, J. C. & Thompson, C. B. ( 2002; ). Pathways of apoptosis in lymphocyte development, homeostasis, and disease. Cell 109 (Suppl.), S97–S107.[CrossRef]
    [Google Scholar]
  35. Ridpath, J. F., Bolin, S. R. & Dubovi, E. J. ( 1994; ). Segregation of bovine viral diarrhea virus into genotypes. Virology 205, 66–74.[CrossRef]
    [Google Scholar]
  36. Ridpath, J. F., Neill, J. D. & Peterhans, E. ( 2007; ). Impact of variation in acute virulence of BVDV1 strains on design of better vaccine efficacy models. Vaccine 25, 8058–8066.[CrossRef]
    [Google Scholar]
  37. Saldeen, J. ( 2000; ). Cytokines induce both necrosis and apoptosis via a common Bcl-2-inhibitable pathway in rat insulin-producing cells. Endocrinology 141, 2003–2010.
    [Google Scholar]
  38. Sánchez-Cordón, P. J., Romanini, S., Salguero, F. J., Núñez, A., Bautista, M. J., Jover, A. & Gómez-Villamos, J. C. ( 2002; ). Apoptosis of thymocytes related to cytokine expression in experimental classical swine fever. J Comp Pathol 127, 239–248.[CrossRef]
    [Google Scholar]
  39. Sánchez-Cordón, P. J., Romanini, S., Salguero, F. J., Ruiz-Villamor, E., Carrasco, L. & Gómez-Villamandos, J. C. ( 2003; ). A histopathologic, immunohistochemical, and ultrastructural study of the intestine in pigs inoculated with classical swine fever virus. Vet Pathol 40, 254–262.[CrossRef]
    [Google Scholar]
  40. Sánchez-Cordón, P. J., Núñez, A., Salguero, F. J., Pedrera, M., Fernández de Marco, M. & Gómez-Villamandos, J. C. ( 2005; ). Lymphocyte apoptosis and thrombocytopenia in spleen during classical swine fever: role of macrophages and cytokines. Vet Pathol 42, 477–488.[CrossRef]
    [Google Scholar]
  41. Savill, J., Fadok, V., Henson, P. & Haslett, C. ( 1993; ). Phagocyte recognition of cells undergoing apoptosis. Immunol Today 14, 131–136.[CrossRef]
    [Google Scholar]
  42. Schweizer, M. & Peterhans, E. ( 1999; ). Oxidative stress in cells infected with bovine viral diarrhoea virus: a crucial step in the induction of apoptosis. J Gen Virol 80, 1147–1155.
    [Google Scholar]
  43. Schweizer, M. & Peterhans, E. ( 2001; ). Noncytopathic bovine viral diarrhea virus inhibits double-stranded RNA-induced apoptosis and interferon synthesis. J Virol 75, 4692–4698.[CrossRef]
    [Google Scholar]
  44. Stahelin, B. J., Marti, U., Solioz, M., Zimmermann, H. & Reichen, J. ( 1998; ). False positive staining in the TUNEL assay to detect apoptosis in liver and intestine is caused by endogenous nucleases and inhibited by diethyl pyrocarbonate. Mol Pathol 51, 204–208.[CrossRef]
    [Google Scholar]
  45. Stennicke, H. R., Jurgensmeier, J. M., Shin, H., Deveraux, Q., Wolf, B. B., Yang, X., Zhon, Q., Ellerby, H. M., Ellerby, L. M. & other authors ( 1998; ). Pro-caspase-3 is a major physiologic target of caspase-8. J Biol Chem 273, 27084–27090.[CrossRef]
    [Google Scholar]
  46. Stoffregen, B., Bolin, S. R., Ridpath, J. F. & Pohlenz, J. ( 2000; ). Morphologic lesions in type 2 BVDV infections experimentally induced by strain BVDV2–1373 recovered from a field case. Vet Microbiol 77, 157–162.[CrossRef]
    [Google Scholar]
  47. Teichmann, U., Liebler-Tenorio, E. M. & Pohlenz, J. F. ( 2000; ). Ultrastructural changes in follicles of small-intestinal aggregated lymphoid nodules in early and advanced phases of experimentally induced mucosal diseases in calves. Am J Vet Res 61, 174–182.[CrossRef]
    [Google Scholar]
  48. Tolskaya, E. A., Romanova, L. I., Kolesnikova, M. S., Ivannikova, T. A., Smirnova, E. A., Raikhlin, N. T. & Agol, V. I. ( 1995; ). Apoptosis-inducing and apoptosis-preventing functions of poliovirus. J Virol 69, 1181–1189.
    [Google Scholar]
  49. Vassilev, V. B. & Donis, R. O. ( 2000; ). Bovine viral diarrhea virus induced apoptosis correlates with increased intracellular viral RNA accumulation. Virus Res 69, 95–107.[CrossRef]
    [Google Scholar]
  50. Walz, P. H., Bell, T. G., Wells, J. L., Gooms, D. L., Kaiser, L., Maes, R. K. & Baker, J. C. ( 2001; ). Relationship between degree of viremia and disease manifestations in calves with experimentally induced bovine viral diarrhoea virus infection. Am J Vet Res 62, 1095–1103.[CrossRef]
    [Google Scholar]
  51. Wilhelmsen, C. L., Bolin, S. R., Ridpath, J. F., Cheville, N. F. & Kluge, J. P. ( 1990; ). Experimental primary postnatal bovine viral diarrhea viral infections in six-month-old calves. Vet Pathol 27, 235–243.
    [Google Scholar]
  52. Yamane, D., Nagai, M., Ogawa, Y., Tohya, Y. & Akashi, H. ( 2005; ). Enhancement of apoptosis via an extrinsic factor, TNF-α, in cells infected with cytopathic bovine viral diarrhea virus. Microbes Infect 7, 1482–1491.[CrossRef]
    [Google Scholar]
  53. Zhang, G., Aldridge, S., Clarke, M. C. & McCauley, J. W. ( 1996; ). Cell death induced by cytopathic bovine viral diarrhoea virus is mediated by apoptosis. J Gen Virol 77, 1677–1681.[CrossRef]
    [Google Scholar]
  54. Zheng, L., Fisher, G., Miller, R. E., Peschon, J., Lynch, D. H. & Lenardo, M. J. ( 1995; ). Induction of apoptosis in mature T cells by tumour necrosis factor. Nature 377, 348–351.[CrossRef]
    [Google Scholar]
  55. Zhuang, S. M., Shvarts, A., van Ormondt, H., Jochemsen, A. G., van der Eb, A. J. & Noteborn, M. H. ( 1995; ). Apoptin, a protein derived from chicken anemia virus, induces p53-independent apoptosis in human osteosarcoma cells. Cancer Res 55, 486–489.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.012021-0
Loading
/content/journal/jgv/10.1099/vir.0.012021-0
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