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The evolution of TSE strains in mixed infections - SE1447

Description
The National Scrapie Plan (NSP) has resulted in a reduction of the incidence of classical scrapie to reported numbers lower than that of atypical scrapie in sheep in the UK. It was an aim of the NSP to reduce frequencies of the VRQ PrP gene allele in sheep, the allele associated with one of the main groups of scrapie strains. Indirectly this has resulted in an increase in the relative numbers of animals encoding ARQ alleles and which will support both atypical and classical scrapie, including strains which have similarities to BSE in Western blot pattern of disease related PrP. These BSE-like strains have in the past produced major concerns that BSE had infected sheep in national flocks and considerable work was required to demonstrate that, although some scrapie strains have BSE-like features, they are not BSE. CH1641 is the archetype of such BSE-like scrapie strains but others have been described throughout Europe. It is possible in the UK that CH1641-like strains could occur in a mixed infection with atypical scrapie, potentially causing BSE-in-sheep scares and but also possibly resulting in the emergence of a novel combined strain with unknown risks for animals and humans. It is important therefore to study CH1641 in more detail.
Previous studies in this lab (SE1429 and SE1436) and elsewhere have observed the changing characteristics of BSE in mixed infections with scrapie in sheep, however it could be argued it is now more likely that CH1641-like classical scrapie strains might be found in mixed infections of sheep with atypical scrapie and nothing is known about this potential phenomenon or the risks developing from such a mixed infection. This proposal aims therefore to address the issue using both sheep and transgenic mice using standard strain typing methodologies to gain information on how mixed scrapie/atypical scrapie infection would appear to those conducting surveillance testing for sheep TSE infections.
The benefits of this proposed study will be realised by increasing our understanding of how TSE strains interact under controlled conditions, particularly those ARQ-targetting strains likely now to predominate in the UK and Europe as a result of breeding against VRQ alleles. It is likely that novel strains will emerge following some kind of selection process during infections in sheep with PrP genotypes not normally affected by scrapie and/or when strains inadvertently interact in rare multiple infections of individuals or flocks. In order to be prepared to deal with emerging TSE strains in the future, this project will provide crucial and different information on strain interactions to that which we have already generated on mixed TSE strain infections for VRQ-targetting scrapie strains in sheep (SE1436) and mice (SE1429). These existing and completed projects will provide tissues for laboratory studies and contribute to minimising costs. Understanding of how ARQ targeting strains of TSEs interact will contribute to the primary objective (2.2) of Defra’s Livestock – TSE and ABP evidence plan 2011/12 which aims to cope with potential threats from new or re-emerging TSEs.
Objective
01 Challenge New Zealand derived ARQ/ARQ Cheviot sheep with CH1641 and atypical scrapie (single strains) and two sets of mixtures, namely 1:1 and 1:4 of CH1641 and atypical scrapie
02 Challenge tg 338 mice (express sheep VRQ PrP gene allele) with the same inocula used for the sheep in objective 01 above.
03 Observe all challenged sheep and mice for signs of illness and test all deaths, intercurrent or TSE related for signs of PrPSc by lesion profiling, immunohistochemistry and Western blotting where appropriate in order to strain type the dominant TSE strain in diseased animals.
04 Challenge tg 338 mice with brain homogenate from the sheep challenged in 01 above to provide a bioassay of the same strains or strain mixtures after passage in sheep
05 Compare results with our previous experiments using several different TSE strains in tg 338 mice including CH1641, atypical scrapie, SSBP/1 and natural scrapie
06 Provide annual and final reports to DEFRA on project progress.
Time-Scale and Cost
From: 2013

To: 2016

Cost: £420,414
Contractor / Funded Organisations
University of Edinburgh
Keywords
Scrapie              
Fields of Study
Animal Health