Abstract
Breeding towards genetic resistance to prion disease is effective in eliminating scrapie. In sheep, classical forms of scrapie have been eradicated almost completely in several countries by breeding programs using a prion protein (PrP) gene (PRNP) amino acid polymorphism. For goats, field and experimental studies have provided evidence for several amino acid polymorphisms that are associated with resistance to scrapie, but only limited data are available concerning the susceptibility of caprine PRNP genotypes to BSE. In this study, goat kids representing five PRNP genotypes based on three polymorphisms (M142, Q211 and K222 and the wild type I142, R211 and Q222) were orally challenged with bovine or goat BSE. Wild type goats were killed with clinical signs between 24–28 months post inoculation (mpi) to both challenges, and goats with genotype R/Q211 succumbed between 29–36 mpi. I/M142 goats developed clinical signs at 44–45 mpi and M/M142 goats remained healthy until euthanasia at 48 mpi. None of the Q/K222 goats showed definite clinical signs. Taken together the highest attack ratios were seen in wild type and R/Q211 goats, and the lowest in I/M142, M/M142 and Q/K222. In all genotype groups, one or more goats remained healthy within the incubation period in both challenges and without detectable PrP deposition in the tissues. Our data show that both the K222 and M142 polymorphisms lengthen the incubation period significantly compared to wild type animals, but only K222 was associated with a significant increase in resistance to BSE infection after oral exposure to both BSE sources.
Highlights
Prion diseases or transmissible spongiform encephalopathies (TSEs) are caused by a unique infectious agent (“prion”) characterised by an entirely proteinaceous nature with apparent absence of functional nucleic acids [1, 2]
Goat challenge results were classified in four health stage categories: (a) clinical—when consistent neurological signs pointing to a bovine spongiform encephalopathy (BSE) infection were observed, (b) late preclinical—when no obvious clinical signs were observed but the animal appeared post mortem positive by IHC in the central nervous system (CNS), (c) early preclinical—when animals showed positivity by IHC in peripheral tissues but not yet in the CNS, and (d) healthy—without any of these markers
The low presence of 12B2 epitope (12B2/Sha31 signal ratio < 0.3), the glycoprofile expressed as the ratio between mono- and diglycosylated PrPres (< 0.4, using glycoform fractions of total PrPres in the Sha31 epitope detection) and the presence of only a single PrPres population pointed out that all positive samples did show the character of a C-type BSE infection (Figure 6B) [48, 49]. This oral challenge study in goats elucidates the significant protection conferred by the Q/K222 prion protein genotype against bovine and goat BSE infection administered through the oral route
Summary
Prion diseases or transmissible spongiform encephalopathies (TSEs) are caused by a unique infectious agent (“prion”) characterised by an entirely proteinaceous nature with apparent absence of functional nucleic acids [1, 2]. The emergence of bovine spongiform encephalopathy (BSE) in cattle and its subsequent transmission to humans as variant Creutzfeld–Jakob disease (vCJD) has proven that prion diseases represent a threat for man and other mammalian species [8, 9]. Goats represent the only other domestic ruminant species to be affected by BSE under field conditions [10,11,12]. Goats are susceptible to classical scrapie the disease occurs in Europe generally at 2–3 times lower prevalence than in sheep [13]. Susceptibility to TSE infection in sheep and goats has a strong genetic component that
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