Immunohistochemical analysis of peripheral lymph nodes from gnotobiotic calves persistently infected with bovine viral diarrhoea virus (BVDV) revealed extensive deposition of E and localization of the viral genome in the light zone of germinal centres. Viral antigen co-localized with immunoglobulin in the germinal centres and was shown to be extracellular. Despite the presence of viral antigen in germinal centres, circulating anti-BVDV antibody was not detected. These findings provide evidence that calves persistently infected with BVDV, in the absence of adventitious infection, can generate a B cell response to the persisting virus. The nature of the tolerance in calves persistently infected with BVDV is discussed in light of these findings.


Article metrics loading...

Loading full text...

Full text loading...



  1. Azazy, A. A., Devaney, E. & Chance, M. L. (1994). A PEG-ELISA for the detection of Leishmania donovani antigen in circulating immune complexes. Transactions of the Royal Society for Tropical Medicine and Hygiene 88, 62-66.[CrossRef] [Google Scholar]
  2. Bachmann, M. F. (1998). The role of germinal centres for antiviral B cell responses. Immunological Research 17, 329-344.[CrossRef] [Google Scholar]
  3. Bachmann, M. F., Odermatt, B., Hengartner, H. & Zinkernagel, R. M. (1996). Induction of long-lived germinal centres associated with persisting antigen after viral infection. Journal of Experimental Medicine 183, 2259-2269.[CrossRef] [Google Scholar]
  4. Bielefeldt Ohmann, H. (1983). Pathogenesis of bovine viral diarrhoea-mucosal disease: distribution and significance of BVDV antigen in diseased calves. Research in Veterinary Science 34, 5-10. [Google Scholar]
  5. Bielefeldt Ohmann, H. (1988). BVD virus antigens in tissues of persistently viraemic, clinically normal cattle: implications for the pathogenesis of clinically fatal disease. Acta Veterinaria Scandinavica 29, 77-84. [Google Scholar]
  6. Bolin, S. R. (1995). The pathogenesis of mucosal disease. Veterinary Clinics of North America 11, 489-498. [Google Scholar]
  7. Brownlie, J., Clarke, M. C. & Howard, C. J. (1984). Experimental production of fatal mucosal disease in cattle. Veterinary Record 114, 535-536.[CrossRef] [Google Scholar]
  8. Collins, M. E., Desport, M. & Brownlie, J. (1999). Bovine viral diarrhea quasispecies during persistent infection. Virology 259, 85-98.[CrossRef] [Google Scholar]
  9. Desport, M., Collins, M. E. & Brownlie, J. (1994). Detection of bovine viral diarrhoea virus RNA by in situ hybridization with digitoxenin-labelled riboprobes. Intervirology 37, 269-276. [Google Scholar]
  10. Duffell, S. J. & Harkness, J. W. (1985). Bovine virus diarrhoea – mucosal disease infection in cattle. Veterinary Record 117, 240-245.[CrossRef] [Google Scholar]
  11. Fray, M. D., Prentice, H., Clarke, M. C. & Charleston, B. (1998). Immunohistochemical evidence for the localisation of bovine viral diarrhoea virus, a single-stranded RNA virus, in ovarian oocytes in the cow. Veterinary Pathology 35, 253-259.[CrossRef] [Google Scholar]
  12. Fritzemeier, J., Haas, L., Liebler, E., Moennig, V. & Greiser-Wilke, I. (1997). The development of early vs late onset mucosal disease is a consequence of two different pathogenic mechanisms. Archives of Virology 142, 1335-1350.[CrossRef] [Google Scholar]
  13. Harlow, E. & Lane, D. (1988).Antibodies: A Laboratory Manual. Cold Spring Harbor: Cold Spring Harbor Laboratory.
  14. Howard, C. J., Clarke, M. C. & Brownlie, J. (1985). An enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to bovine viral diarrhoea virus (BVDV) in cattle sera. Veterinary Microbiology 10, 359-369.[CrossRef] [Google Scholar]
  15. Lennard, S. N., Stewart, F. & Allen, W. R. (1995). IGF-II gene expression in the fetus and placenta of the horse during the first half of gestation. Journal of Reproduction and Fertility 130, 169-179. [Google Scholar]
  16. Liu, Y.-J. & Arpin, C. (1997). Germinal centre development. Immunological Reviews 156, 111-126.[CrossRef] [Google Scholar]
  17. Oldstone, M. B. A. & Dixon, F. J. (1967). Lymphocytic choriomeningitis: production of antibody by ‘tolerant’ infected mice. Science 158, 1193-1195.[CrossRef] [Google Scholar]
  18. Paton, D. J., Gunn, M., Sands, J., Yapp, F., Drew, T., Vilcek, S. & Edwards, S. (1997). Establishment of serial persistent infections with bovine viral diarrhoea virus in cattle and sheep and changes in epitope expression related to host species. Archives of Virology 142, 929-938.[CrossRef] [Google Scholar]
  19. Rümenapf, T., Unger, G., Strauss, J. H. & Thiel, H.-J. (1993). Processing of the envelope glycoproteins of pestiviruses. Journal of Virology 67, 3288-3294. [Google Scholar]
  20. Susa, M., Konig, M., Saalmüller, A., Reddehase, J. M. & Thiel, H.-J. (1992). Pathogenesis of classical swine fever: B-lymphocyte deficiency caused by hog cholera virus. Journal of Virology 66, 1171-1175. [Google Scholar]
  21. Tew, J. G., Wu, J., Qin, D., Helm, S., Burton, G. F. & Szakal, A. K. (1997). Follicular dendritic cells and presentation of antigen and costimulatory signals to B cells. Immunological Reviews 156, 39-52.[CrossRef] [Google Scholar]
  22. Weiland, F., Weiland, E., Unger, G., Saalmüller, A. & Thiel, H.-J. (1999). Localization of pestiviral envelope proteins Erns and E2 at the cell surface and on isolated particles. Journal of General Virology 80, 1157-1165. [Google Scholar]
  23. Williams, D. J. L., Newson, J. & Naessens, J. (1990). Quantitation of bovine immunoglobulin isotypes and allotypes using monoclonal antibodies.Veterinary Immunology and Immunopathology 24, 267-284.[CrossRef] [Google Scholar]
  24. Zhang, G., Aldridge, S., Clarke, M. C. & McCauley, J. W. (1996). Cell death induced by cytopathic bovine viral diarrhoea virus is mediated by apoptosis. Journal of General Virology 77, 1677-1681.[CrossRef] [Google Scholar]

Data & Media loading...

Most cited this month Most Cited RSS feed

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