Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice.

Alba Marín-Moreno,Naima Aron,Patricia Lorenzo,Jean Yves Douet,Sévérine Lugan,Alvina Huor,Cecile Tillier,Juan María Torres,Hervé Cassard,Patricia Aguilar-Calvo,Juan Carlos Espinosa,Olivier Andreoletti,Juan Píquer

doi:10.3201/eid2606.181790

Abstract

Classical bovine spongiform encephalopathy (BSE) is the only zoonotic prion disease described to date. Although the zoonotic potential of atypical BSE prions have been partially studied, an extensive analysis is still needed. We conducted a systematic study by inoculating atypical BSE isolates from different countries in Europe into transgenic mice overexpressing human prion protein (PrP): TgMet129, TgMet/Val129, and TgVal129. L-type BSE showed a higher zoonotic potential in TgMet129 mice than classical BSE, whereas Val129-PrP variant was a strong molecular protector against L-type BSE prions, even in heterozygosis. H-type BSE could not be transmitted to any of the mice. We also adapted 1 H- and 1 L-type BSE isolate to sheep-PrP transgenic mice and inoculated them into human-PrP transgenic mice. Atypical BSE prions showed a modification in their zoonotic ability after adaptation to sheep-PrP producing agents able to infect TgMet129 and TgVal129, bearing features that make them indistinguishable of sporadic Creutzfeldt-Jakob disease prions.

Highlights

Classical bovine spongiform encephalopathy (BSE) is the only zoonotic prion disease described to date
Classical bovine spongiform encephalopathy (CBSE) caused a major food safety crisis when consumption of contaminated meat was discovered in the late 1990s as the cause of a new prion disease affecting humans, which was called variant Creutzfeldt-Jakob disease [4]
As we reported on a previous study [18], only TgMet129 mice get infected with C-BSE isolates

Summary

Introduction

Classical bovine spongiform encephalopathy (BSE) is the only zoonotic prion disease described to date. We conducted a systematic study by inoculating atypical BSE isolates from different countries in Europe into transgenic mice overexpressing human prion protein (PrP): TgMet129, TgMet/Val129, and TgVal129. Atypical BSE prions showed a modification in their zoonotic ability after adaptation to sheep-PrP producing agents able to infect TgMet129 and TgVal129, bearing features that make them indistinguishable of sporadic Creutzfeldt-Jakob disease prions. The biochemical properties of PrPSc isolated from these cases differed from C-BSE in terms of the protease-resistant fragment size and ratio of glycoforms on Western blot (WB). It is unclear whether atypical BSE resulted from exposure to an acquired. TSE or emerged spontaneously, a theory supported by the occurrence of atypical BSE being maintained at a similar rate in various countries independent of their C-BSE status

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