Abstract
(Englisch)
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The intracellular parasite Theileria annulata causes tropical theileriosis, a disease of cattle that constitutes a major obstacle to livestock production in large areas of Northern Africa, the Middle East and Iran, stretching all the way to India. It is closely related to Theileria parva, which causes East Coast fever of cattle in East and Central Africa. Both parasites are transmitted by ticks and various attempts have been made, with restricted success, to generate vaccines that target the tick-transmitted stage of the parasite, the sporozoite. The next stage in the parasite life cycle, the schizont, can be found in the host's leukocytes and is pathogenic in both Theileria species. In T. annulata, merozoites, which develop upon further differentiation of the schizont in a process called merogony, are also pathogenic and can be found in the erythrocytes where they undergo multiplication. The aim of the TANVAC programme is to develop molecular vaccines and diagnostics for the control of tropical theileriosis. Different laboratories target different stages of the parasite. The schizont stage of the parasite causes most of the pathology in the infected animal and is also instrumental for the spread of the parasite throughout the body. Although protective epitopes are expressed on the surface of Theileria-infected cells, the antigens encoding these epitopes have remained elusive for many years. The Theileria laboratory of the Division of Molecular Pathology at the Institute of Animal Pathology has concentrated its efforts on the schizont stage. In earlier work, we have found that the schizont stage of Theileria interferes directly with an important host cell signalling pathway (the NFkB pathway) that contributes to the continuous proliferation of the infected cell and prevents its apoptosis. We have recently shown that activating kinase complexes that are pivotal in the control NF-kB activation are recruited to the surface of the schizont. Our approach is to attempt to identify parasite proteins that interact with this kinase complex, the rationale being that such antigen(s) will contribute directly to the pathogenesis of the disease and, by virtue of the fact that they are exposed to or secreted into the host cell cytoplasm, are bound to form good targets for cell-mediated immune responses. Such responses have been shown to provide the most efficient protection against reinfection in animals that have survived theileriosis. In the past year, we have focussed on establishing yeast two hybrid technology to search for parasite proteins that interact with components of the NF-kB activation pathway. We have recently observed that parasite schizont surface antigens can undergo phosphorylation. Such modifications may be crucial for the interaction with host cell proteins and it can not be excluded that the correct phosphorylation does not occur in yeast. We have therefore extended our approach to pull-down and co-precipitation experiments.
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