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

Romolo Nonno,Frédéric Lantier ,Christine Fast,Juan Carlos Espinosa,Theodoros Sklaviadis,J.g Jacobs ,Cristina Acín ,John Spiropoulos,Umberto Agrimi,Patricia Aguilar‐Calvo ,Juan María Torres ,Martin H Groschup,Pier Luigi Acutis,Olivier Andréoletti ,Alex Bossers,Claudia D’Agostino,Barbara Chiappini,Penelope Papasavva-Stylianou,Lucien Van Keulen,Michele Angelo Di Bari ,Alba Marín-Moreno ,Isabelle Lantier,Laura Pirisinu,Gabriele Vaccari,J.p.m Langeveld

doi:10.1038/s41598-019-57005-6

Abstract

Bovine Spongiform Encephalopathy (BSE) is the only animal prion which has been recognized as a zoonotic agent so far. The identification of BSE in two goats raised the need to reliably identify BSE in small ruminants. However, our understanding of scrapie strain diversity in small ruminants remains ill-defined, thus limiting the accuracy of BSE surveillance and spreading fear that BSE might lurk unrecognized in goats. We investigated prion strain diversity in a large panel of European goats by a novel experimental approach that, instead of assessing the neuropathological profile after serial transmissions in a single animal model, was based on the direct interaction of prion isolates with several recipient rodent models expressing small ruminants or heterologous prion proteins. The findings show that the biological properties of scrapie isolates display different patterns of geographical distribution in Europe and suggest that goat BSE could be reliably discriminated from a wide range of biologically and geographically diverse goat prion isolates. Finally, most field prion isolates showed composite strain features, with discrete strain components or sub-strains being present in different proportions in individual goats or tissues. This has important implications for understanding the nature and evolution of scrapie strains and their transmissibility to other species, including humans.

Highlights

Transmissible spongiform encephalopathies (TSEs) or prion diseases include fatal neurological diseases of humans and animals which can have different origin and epidemiology, i.e. acquired, sporadic or familial
Two of the isolates from the panel were an Italian goat with atypical scrapie (I15)[34] and an unusual goat case with 19 K PrPSc originating from a large scrapie outbreak in an English herd[28], later shown to have strain properties distinct from BSE35 and clearcut CH1641-like biochemical features (UKB2)[33]
The details of rodent models and their overall ability to propagate goat prions are presented in Table 2; the individual attack rates and survival times of all inoculated rodent lines for 33 isolates are reported in Supplementary Table S1

Summary

Introduction

Transmissible spongiform encephalopathies (TSEs) or prion diseases include fatal neurological diseases of humans and animals which can have different origin and epidemiology, i.e. acquired, sporadic or familial. Humans may be exposed to TSE infected tissues of animal origin through the food chain Some of these TSEs in animals, such as chronic wasting disease (CWD) in cervids and classical scrapie in sheep and goats, efficiently spread by natural transmission and are infectious under field conditions. Intensified surveillance in the EU allowed to identify molecular and pathological properties reminiscent of experimental CH1641 in naturally affected sheep and goats ;12,24,25,27,28 these cases have been often referred to as CH1641-like scrapie. Goat scrapie strains have been less investigated and very little knowledge has been gathered on scrapie strain diversity in goats, limiting the accuracy and reliability of BSE surveillance in goats This knowledge is necessary both for the ability to properly identify BSE in small ruminants and for the understanding of the zoonotic potential of scrapie

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Conclusion