TSEs in European goats discriminated by Western blotting into five types based on five robust molecular parameters

Contrasting the knowledge about prion diseases or TSEs in sheep, only a very limited number of strain typing studies are available in goats. Two cases deriving from the zoonotic bovine BSE epidemic were however detected in goats. During 2004–2012, over 70 TSE goat brain samples were collected from seven European countries and evaluated for TSE type/strain variation. A selection of these materials was chosen for in-depth analysis based on various criteria: tissue quality, genotype, broad geographical distribution, potential type variation. Of these, 37 cases were biochemically analysed (present study) and a subset of these subjected to bioassays in seven rodent models (see parallel study of Nonno et al.). Analyses of these isolates showed that in goats different PrPSc types exist, comparable to those found in sheep such as classical scrapie, CH1641-like scrapie and Nor98/atypical scrapie. However, classical scrapie isolates could be further differentiated in two molecular subtypes based on the PK susceptibility of the N-terminus and on the molecular weight of PrPres. Importantly, the two subtypes of classical scrapie showed different geographical distribution, as one subtype was only detected in goats deriving from Italy and France. These analyses also show, that none of the field samples exhibited BSE-like features and offer a comprehensive set of robust molecular PrPres properties to exclude suspicion for the presence of BSE. These are: molecular mass of the triplet bands, presence of N-terminus epitope, glycoprofile markers, a dual population marker and the structural stability of PrP-core. This work was made possible by national support and by the following European grants: Neuroprion (FP6-FOOD-506,579), GoatBSE (FOOD-CT-2006–36,353) and GOAT-TSE-FREE (EMIDA-ERA NET). We want to memorize Jorg G Jacobs, who died in 2017. Jorg developed and performed the Triplex-WB system as well as characterized antibodies like 94B4, 12B2, 9A2, 6C2, SAF84 and L42. He also was crucial in the distinction of C-, L- and H-type BSE and in 2011 he showed elegantly the allotype composition of prion material in heterozygous sheep by the use of Endo-LysC.