Four types of scrapie in goats differentiated from each other and bovine spongiform encephalopathy by biochemical methods

Abstract

Scrapie in goats has been known since 1942, the archetype of prion diseases in which only prion protein (PrP) in misfolded state (PrPSc) acts as infectious agent with fatal consequence. Emergence of bovine spongiform encephalopathy (BSE) with its zoonotic behaviour and detection in goats enhanced fears that its source was located in small ruminants. However, in goats knowledge on prion strain typing is limited. A European-wide study is presented concerning the biochemical phenotypes of the protease resistant fraction of PrPSc (PrPres) in over thirty brain isolates from transmissible spongiform encephalopathy (TSE) affected goats collected in seven countries. Three different scrapie forms were found: classical scrapie (CS), Nor98/atypical scrapie and one case of CH1641 scrapie. In addition, CS was found in two variants—CS-1 and CS-2 (mainly Italy)—which differed in proteolytic resistance of the PrPres N-terminus. Suitable PrPres markers for discriminating CH1641 from BSE (C-type) appeared to be glycoprofile pattern, presence of two triplets instead of one, and structural (in)stability of its core amino acid region. None of the samples exhibited BSE like features. BSE and these four scrapie types, of which CS-2 is new, can be recognized in goats with combinations of a set of nine biochemical parameters.

Characterization of goat prions demonstrates geographical variation of scrapie strains in Europe and reveals the composite nature of prion strains

“…No obvious correlation was identified between the presence of additional PrP polymorphisms and poor transmissibility in one or more rodent models ( Supplementary Table S1). Furthermore, no relation appeared between lack of transmissibility in some rodent models and PrP Sc quantities in the goat brain macerate as estimated by triplex-WB 33 . Overall, these findings show that the transmission rate in different rodent models did not depend simply on the overall low susceptibility of a given model, the low infectious titer or PrP res level of given isolates or the PrP genotype of the donor goat, but reflected different biological properties of the TSE isolates instead.…”

“…Most of the isolates had the classical scrapie PrP Sc type, hereafter referred to as "21 K", which can be discriminated from experimental BSE in goat by the lower MM (referred to as "19 K") and the reduced binding with mAb P4 8 . Two of the isolates from the panel were an Italian goat with atypical scrapie (I15) 34 and an unusual goat case with 19 K PrP Sc originating from a large scrapie outbreak in an English herd 28 , later shown to have strain properties distinct from BSE 35 and clearcut CH1641-like biochemical features (UKB2) 33 .…”

“…As the P-to-S PrP polymorphism at codon 240 is exceedingly frequent in EU goats, the amino acids at this position are reported for all goats. § The PrP Sc type was determined by analyzing the same brain macerates here used for transmission studies 33 . § § This case was found to have unusual 19 K PrP Sc type in the brain 28 , but strain properties distinct from BSE ; 35 we later identified CH1641-like PrP Sc properties in this isolate 33 .…”

“…We selected a panel of EU goat TSE isolates and characterised their molecular and biological properties in different EU labs. While the detailed molecular features of PrP Sc in the chosen goat TSE isolates panel will be reported elsewhere in parallel 33 , we here report the results of the bioassay experiments. Importantly, all experiments were done with aliquots of the same brain macerates, so as to reduce any sampling bias and to allow proper comparison of different animal models.…”

Novel Variations in Native Ethiopian Goat breeds PRNP Gene and Their Potential Effect on Prion Protein Stability

“…A recent work by Langeveld Pirisinu et al 2019 summarized goat scrapie forms and the respective genotypes implicated in each form from different study cases. Genotypes of 127GS, 143HR, 211QR, 240PP, and 240PS were classified under two variants of classical scrapie (CS-1 & CS-2) while 145RH and 240PS were under atypical scrapie (AS) 35 . Accordingly, due to the absence or low frequency of the majority of resistant genotypes, the breeds under study were less resitant to both classical and atypical scrapie.…”