Abstract

BackgroundPrevious studies confirmed that classical scrapie can be transmitted via milk in sheep. The current study aimed to investigate whether scrapie can also be transmitted via goat milk using in vivo (new-born lambs fed milk from scrapie-affected goats due to the unavailability of goat kids from guaranteed scrapie-free herds) and in vitro methods (serial protein misfolding cyclic amplification [sPMCA] on milk samples).ResultsIn an initial pilot study, new-born lambs of two different prion protein gene (PRNP) genotypes (six VRQ/VRQ and five ARQ/ARQ) were orally challenged with 5 g brain homogenate from two scrapie-affected goats to determine susceptibility of sheep to goat scrapie. All sheep challenged with goat scrapie brain became infected based on the immunohistochemical detection of disease-associated PrP (PrPsc) in lymphoid tissue, with an ARQ/ARQ sheep being the first to succumb. Subsequent feeding of milk to eight pairs of new-born ARQ/ARQ lambs, with each pair receiving milk from a different scrapie-affected goat, resulted in scrapie in the six pairs that received the largest volume of milk (38–87 litres per lamb), whereas two pairs fed 8–9 litres per lamb, and an environmental control group raised on sheep milk from healthy ewes, did not show evidence of infection when culled at up to 1882 days of age. Infection in those 12 milk recipients occurred regardless of the clinical status, PrPsc distribution, caprine arthritis-encephalitis virus infection status and PRNP polymorphisms at codon 142 (II or IM) of the donor goats, but survival time was influenced by PRNP polymorphisms at codon 141. Serial PMCA applied to a total of 32 milk samples (four each from the eight donor goats collected throughout lactation) detected PrPsc in one sample each from two goats.ConclusionsThe scrapie agent was present in the milk from infected goats and was able to transmit to susceptible species even at early preclinical stage of infection, when PrPsc was undetectable in the brain of the donor goats. Serial PMCA as a PrPsc detection method to assess the risk of scrapie transmission via milk in goats proved inefficient compared to the bioassay.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-016-0807-4) contains supplementary material, which is available to authorized users.

Highlights

  • Previous studies confirmed that classical scrapie can be transmitted via milk in sheep

  • Sheep A1473 was the one with the earliest detectable PrPsc in palatine tonsil (266 days of age), which is why the ARQ/ARQ genotype was selected for milk recipients in the subsequent milk transmission study

  • All sheep orally dosed with goat brain developed clinical signs of scrapie and this was confirmed by IHC examination of the brain

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Summary

Introduction

Previous studies confirmed that classical scrapie can be transmitted via milk in sheep. Previous transmission studies had only confirmed the susceptibility of goats to sheep scrapie by natural or oral infection [9, 10] but not vice-versa. A pilot study was initiated to determine whether sheep were susceptible to goat scrapie following oral challenge with brain homogenate, which would mimic the route for a further milk transmission experiment, and to assess which genotype, VRQ/VRQ or ARQ/ARQ, was more susceptible. The findings are compared with those of serial Protein Misfolding Cyclic Amplification (sPMCA) applied to goat milk, since this method had been able to detect PrPsc in milk samples from scrapie-affected sheep, which transmitted scrapie to lambs [3]

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