Comparative susceptibility of New Zealand sheep with a range of PRNP genotypes to challenge with bovine spongiform encephalopathy and scrapie

Fiona Houston, Wilfred Goldmann, Jim Foster, Silvia Siso, Lorenzo Gonzalez, Martin Jeffrey, Nora Hunter

Research output: Contribution to journalMeeting abstract

Abstract

Polymorphisms of the sheep Prnp gene have been linked to susceptibility and resistance to classical and atypical scrapie and bovine spongiform encephalopathy (BSE). The three most significant polymorphisms originally identified occur at codons A136V, R154H and Q171R, and there is now evidence that additional PRNP polymorphisms have an influence on survival times (e.g. M112T). Following the emergence of variant Creutzfeld-Jakob disease (vCJD) in humans as a result of exposure to BSE, there were heightened concerns about the possible presence of BSE in the sheep population. To assist with research into the pathogenesis of BSE and scrapie, sheep were imported to the UK from New Zealand to establish a scrapie-free breeding flock. Since it was not known whether other genetic factors, apart from Prnp genotype, would influence the susceptibility of New Zealand sheep to prion infection, the aim of this study was to determine their response to experimental challenge with BSE and the scrapie isolate SSBP/1.
Groups of 5-10 sheep of three different breeds and six Prnp genotypes (VRQ/VRQ, VRQ/ARQ, VRQ/ARR, ARQ/ARQ, ARQ/ARR, ARR/ARR) were challenged either by intracerebral inoculation of BSE or by subcutaneous inoculation of SSBP/1. The sheep were monitored over a period of >10 years for the development of clinical signs. Brain and lymphoid tissues samples from each sheep were analysed for detection of disease-associated PrP (PrPd or PrPSc). Additional genetic analysis was carried out as the effect of other Prnp codons became known. Attack rates and incubation periods were compared with those observed following similar challenges of sheep from the Roslin Scrapie Flock.
Preliminary results gave the first indication that ARR/ARR sheep are susceptible to BSE infection [1]. The complete results show that differing proportions of sheep of all Prnp genotypes tested were susceptible to BSE. There were no major differences in susceptibility between the New Zealand sheep and the Roslin Scrapie Flock, with the exception of ARQ/ARQ sheep challenged with SSBP/1, which were completely susceptible in the former and resistant in the latter. The 141 codon genotype was shown to significantly influence incubation times in both BSE- and scrapie-infected sheep, although with more marked effects in the former. This study is one of the only large scale comparative studies of susceptibility to BSE across a wide range of genotypes. And also suggests non-PRNP genetic effects on susceptibility to peripheral challenge with scrapie.
Original languageEnglish
Pages (from-to)102
Number of pages1
JournalPrion
Volume8
Issue numberSuppt.
Publication statusPublished - May 2014
EventPrion 2014 - Trieste, Italy, United Kingdom
Duration: 24 May 201430 Jun 2014

Keywords

  • prion
  • scrapie
  • sheep
  • prnp genetics

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