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Pathogenesis of classical swine fever; towards rapid immunodiagnostic detection of infected animals

Ziel

Classical swine fever (CSF) is an economically important, often fatal, highly contagious disease of Suidae. The 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 of pigs. This lest description is clearly evident from the situation 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, plus the concomitant trace restrictions which follow. 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 celle, indicating that the 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 7 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 prograrnmed cell death and modulation of differentiation/maturation. Therein, the role of leukocyte factors would be studied, in terms of their roles as soluble mediators of immunological function and signalling. From this work, it is envisagea that a clearer picture of the characteristics of the immunopathology of CSF would be forthcoming 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.

Towards 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 myeloid cells - known to be early targets for the virus. The immunomodulatory activity exerted on and by infected myeloid cells will be assessed in terms of
(i) the factors produced by the infected celle,
(ii) the characteristics of the influence of these factors on haematopoiesis, lymphocyte proliferation, and endothelial cell function (as accessory celle), and
(iii) the role played by these factors in the induction of apoptosis in leukocytes.

Through these analyses, it would be possible to understand more clearly how the disease develops, and how it might be combated. Overall, the immunopathological characteristics of CSF would 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 potentiel existe for a particularly early identification of infected animals - immunodiagnosis - permitting identification of infected animals days before virus detection or seroconversion, and a rapid execution of control measures which should result in a more efficient restriction of the disease and its spread.

Wissenschaftliches Gebiet (EuroSciVoc)

CORDIS klassifiziert Projekte mit EuroSciVoc, einer mehrsprachigen Taxonomie der Wissenschaftsbereiche, durch einen halbautomatischen Prozess, der auf Verfahren der Verarbeitung natürlicher Sprache beruht. Siehe: Das European Science Vocabulary.

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BUNDESFORSCHUNGSANSTALT FUR VIRUSKRANKHEITEN DER TIERE
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