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Measurement of prion infectivity in blood during TSE disease - SE1780

Description
There is concern that iatrogenic manipulations such as blood transfusions or parenteral administration of human biological products may result in transmission of variant Creutzfeldt-Jacob disease (vCJD). This has arisen because the cellular tropism of these new human prions is not fully established. BSE prions appear to have a low affinity for bovine lymphoid tissue whilst in vCJD cases, which are believed to occur through the consumption of BSE-contaminated bovine products, PrPSc may be detected in tonsillar and appendix tissue. The appearance of vCJD prions in extracerebral sites raises the distinct possibility that the infectious agent may also reside in human blood.

The proposal outlined here will investigate scrapie in sheep as a model of vCJD in humans to specifically address the question of whether prion infectivity can be detected in blood during natural TSE disease. Scrapie in sheep is a suitable animal model of vCJD for the following reasons: scrapie is a natural disease of sheep; the localisation of PrPSc in sheep peripheral lymphoid tissue resembles that seen in vCJD; sheep are susceptible to infection with BSE; blood from TSE infected sheep has been shown to contain infectivity.

The objective of this proposal is twofold. Firstly, to establish the transmission characteristics of different ovine prion inoculum in a panel of mice transgenic for either ovine or bovine PrP. Secondly, to use this panel of transgenic mice to measure prion infectivity in blood, lymphoid fluid and lymphoid tissue of scrapied sheep. The specific aims of the proposal are to:
(i) establish the transmission characteristics of ovine prion inoculum in mice transgenic for either ovine PrPARQ ovine PrPVRQ or bovine PrPBo;
(ii) concentrate infectivity from blood isolated from scrapied sheep; (iii) measure the level of prion infectivity in blood from scrapied sheep using the panel of ovine or bovine PrP transgenic mice;
(iv) compare the molecular profile of PrPSc in prion inoculated ovine PrPARQ and ovine PrPVRQ transgenic mice.

Collectively, this analysis of ovine or bovine PrP transgenic mice will establish the usefulness of these indicator mice as a sensitive bioassay with which to assess infectivity in the peripheral blood of scrapied sheep and to determine if different ovine prion strains can be distinguished by transmission characteristics and PrPSc molecular profile. The experiments will also provide novel and useful information for the assessment of the risks associated with vCJD transmission from human blood.
Project Documents
• Final Report : Final Report   (7131k)
Time-Scale and Cost
From: 2003

To: 2007

Cost: £478,144
Contractor / Funded Organisations
University - Cambridge
Keywords
Animal Health              
Bio-assay              
Diagnosis              
Plants and Animals              
Scrapie              
Transgenic              
TSE              
TSEs              
Fields of Study
Animal Health