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Pathogenesis of classical swine fever: towards a rapid immunodiagnostic detection of infected animals

Contract nr: FAIR-CT97-3732
Project nr: 3732
Project type: SC
Starting date: 01/02/1998
Duration: 42 months
Total cost: 1,328,000 EUR
EC Contribution: 775,000 EUR
Scientific Officer: Isabel MINGUEZ-TUDELA
Research topic: Animal health

Classical swine fever (CSF) is an often fatal, highly contagious disease of Suidae that has great economic consequences. Its causative agent - CSFV - is a member of the genus Pestivirus, family Flaviviridae, along with bovine viral diarrhoea and border disease viruses. It is an OIE List A virus, the disease having been described as the most devastating disease pigs can have. This is clearly evident from the status of CSF in the EU during the first two months of 1997, with thousands of pigs having to be slaughtered in Germany, Holland and Italy, compounded with the concomitant trace restrictions which followed.

Experimentation in vivo has identified haematological changes, in particular peripheral blood lymphocyte depletion, and mobilisation of immature granulocytes. These are detectable before virus infection of blood cells, indicating that pathological mechanisms are not a direct consequence of virus infection: lymphocyte depletion was noted as early as one day p.i. with virulent CSFV, whereas virus infection was not clearly detectable before seven days p.i., and seroconversion even later. Based on the evidence currently available, the hypothesis is that the pathogenesis of CSF involves tissue destruction and cell death, induced, at least in part, by the modulation of monocyte/macrophage factors and cellular activity.

The objective of the project is to relate the activity of the infected cells to the form of leukocyte compromisation identified, particularly in terms of programmed cell death and modulation of differentiation/maturation. Therein, the role of leukocyte factors will be studied, in terms of their roles as soluble mediators of immunological function and signalling. It is envisaged that as a result of this work, there will be a clearer picture of the characteristics of the immunopathology of CSF. Consequently, the project has as its primary aim the identification of early immunodiagnostic possibilities in the domain of CSF. That is, the immunological characteristics of the disease which are identifiable before virus detection or identifiable seroconversion. To reach this goal, it is necessary to elucidate the immunopathological mechanisms involved in the compromisation of the immune system during CSF, and how this relates to virus infection of the myeloid cells - which are known to be early targets for the virus.

The immunomodulatory activity exerted on and by infected myeloid cells will be assessed in terms of:

1) the factors produced by the infected cell;
2) the characteristics of the influence of these factors on haematopoiesis, lymphocyte proliferation, and endothelial cell function (as accessory cell);
3) the role played by these factors in the induction of apoptosis in leukocytes.

Through these analyses, it should be possible to understand more clearly how the disease develops, and how it might be combatted. Overall, the immunopathological characteristics of CSF should become clearer. It is already known that certain clear immunomodulations can be seen very early during CSF - before virus infection or seroconversion can be identified by the most rapid and modem techniques currently available. Consequently, the potential exists for a particularly early identification of infected animals - immunodiagnosis - allowing for the identification of infected animals days before virus detection or seroconversion, and thereby allowing for a rapid execution of control measures, which should result in a more efficient restriction of the disease and its spread.

Bundesforschungsanstalt fuer Viruskrankheiten der Tiere
Paul-Ehrlich Str. 28
D-72076 Tuebingen
Tel.: +49 7071 967 256
Fax: +49 7071 967 303


  • Kenneth MCCULLOUGH
    Forschungsanstalt des Bundesamtes fuer Veterinärwesen
    Research Institute of the Swiss Federal Veterinary Office
    Sensemattstrasse 293
    CH-3147 Mittelhäusern
    Tel.: +41 318 48 93 61
    Fax: +41 318 48 92 22

  • Francisco SOBRINO
    Consejo Superior de Investigaciones Cientificas
    Serrano 113
    E-28006 Madrid
    Tel.: +34 91 620 23 00
    Fax: +34 91 620 22 47

  • Brian ADAIR
    The Queen's University of Belfast
    Malone Road 8
    UK-BT9 5BN Belfast
    Tel.: +44 1232 52 56 72
    Fax: +44 1232 52 57 73

  • Gunnar ALM
    Swedish University of Agricultural Sciences
    Division of Immunology
    Department of Veterinary Microbiology
    S-75007 Uppsala
    Tel.: +46 18 17 45 33
    Fax: +46 18 17 43 82

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