Proteins as markers of TSE infection in sheep blood

Transmissible spongiform encephalopathies (TSEs) are a group of fatal infectious neurodegenerative diseases affecting both humans and agricultural animals. TSE transmission via blood transfusion has been demonstrated experimentally in rodent, primate and sheep models. Additionally, in humans, four variant Creutzfeld-Jakob disease (vCJD) cases have been reported which probably resulted from infected blood transfusions. Although TSEs can be transmitted via blood transfusion, little is known about which blood cells are involved in the replication of the TSE agent and how infectivity is spread throughout the body prior to neuroinvasion. There are no currently validated diagnostic tests for TSE infection in blood.<br/>Detection of PK-resistant PrPSc has been extensively used as a biochemical marker for TSE infectivity. However, when this project was started it was not known if PKresistant PrPSc was present in TSE-infected sheep blood in sufficient quantities to explain the infectivity levels shown by bioassay. Following the development of an optimised Western blot method, this project has demonstrated that the pattern of protein detected with novel anti-PrP monoclonal antibodies is very different from the conventional triple banded pattern of PK-resistant PrPSc. High molecular weight bands were apparent in phosphotungstic acid (NaPTA) concentrated scrapie-infected and uninfected blood and may represent a novel form of blood-specific PrP. PK-resistant PrPSc is not therefore a suitable marker for TSE infection in blood.<br/>Other proteins in TSE infected blood were also investigated. Using a proteomics approach three protein markers, lactate dehydrogenase, elongation factor 1 and annexin 1 had altered expression patterns in scrapie infected blood. These proteins, in addition to the novel forms of PrP found in blood, may provide new information on the mechanisms of pathogenesis in scrapie-infected sheep and might prove to be useful molecular indicators of diagnostic value.

Name dc:type.qualificationname

Ph.D.

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of Southampton

Year dc:date.issued

2008

Author dc:creator

• Martin, Joanne

Advisor dc:contributor.advisor

• Perry, V.H.