Classical scrapie in small ruminants is caused by at least four different prion strains

Abstract

The diversity of goat scrapie strains in Europe has recently been studied using bioassays in a wide collection of rodent models, resulting in the classification of classical scrapie into four different categories. However, the sole use of the first passage does not lead to isolate adaptation and identification of the strains involved and might therefore lead to misclassification of some scrapie isolates. Therefore, this work reports the complete transmission study of a wide collection of goat transmissible spongiform encephalopathy (TSE) isolates by intracranial inoculation in two transgenic mouse lines overexpressing either small ruminant (TgGoat-ARQ) or bovine (TgBov) PrPC. To compare scrapie strains in sheep and goats, sheep scrapie isolates from different European countries were also included in the study. Once the species barrier phenomenon was overcome, an accurate classification of the isolates was attained. Thus, the use of just two rodent models allowed us to fully differentiate at least four different classical scrapie strains in small ruminants and to identify isolates containing mixtures of strains. This work reinforces the idea that classical scrapie in small ruminants is a prion disease caused by multiple different prion strains and not by a single strain, as is the case for epidemic classical bovine spongiform encephalopathy (BSE-C). In addition, the clear dissimilarity between the different scrapie strains and BSE-C does not support the idea that classical scrapie is the origin of epidemic BSE-C.

Characterization of the First Case of Classical Scrapie in a Sheep in Tunisia

“…Molecular investigations and bioassays in rodent models allowed to establish that at least four different strains of classical scrapie do exist [48][49][50]. As regard the prion involved in the Tunisian scrapie case, its molecular signature was typical of classical scrapie and different from both BSE and atypical scrapie.…”

Diagnosis in Scrapie: Conventional Methods and New Biomarkers

“…Classical and atypical scrapie differ in their pathogenesis and transmission. Classical scrapie affects goats and sheep from 2 to 5 years of age, and its infectious nature is well known; it is a highly heterogeneous disease as it can be caused by several different prion strains [15]. On the other hand, atypical scrapie is caused by a single strain (Nor98), which usually affects goats and sheep older than 5 years; atypical scrapie cases seem to be sporadic in nature, although several studies have demonstrated the infectious character of this strain [15][16][17].…”

Strain Typing of Classical Scrapie and Bovine Spongiform Encephalopathy (BSE) by Using Ovine PrP (ARQ/ARQ) Overexpressing Transgenic Mice

“…Previous strain typing studies in transgenic mice have identified at least five prion strains responsible for classical scrapie [ 19 , 30 , 31 ], but the exact number is unknown and most field isolates even contain sub-strains at different proportions [ 29 , 32 ]. Evidently, some isolates are not completely stable and different replication environments might play an important role in defining their biological properties, which can shift on transmission and even affect the ability of certain strains to cross the species barrier [ 19 ], as was shown for some classical scrapie isolates in humanized transgenic mice [ 33 ].…”