L-BSE experimentally transmitted to sheep presents as a unique disease phenotype.

Marion M Simmons,Leigh Thorne,Timm Konold,Melanie J Chaplin,Cristina Casalone,Derek Clifford,Katy E Beck,Tobias Floyd,Sharon Everitt,John Spiropoulos

doi:10.1186/s13567-016-0394-1

Abstract

Apart from prion protein genotype, the factors determining the host range and susceptiblity for specific transmissible spongiform encephalopathy agents remain unclear. It is known that bovine atypical L-BSE can transmit to a range of species including primates and humanised transgenic mice. It is important, therefore, that there is as broad an understanding as possible of how such isolates might present in food animal species and how robust they are on inter- and intra-species transmission to inform surveillance sytems and risk assessments. This paper demonstrates that L-BSE can be intracerebrally transmitted to sheep of several genotypes, with the exception of ARR/ARR animals. Positive animals mostly present with a cataplectic form of disease characterized by collapsing episodes and reduced muscle tone. PrP accumulation is confined to the nervous system, with the exception of one animal with lymphoreticular involvement. In Western blot there was maintenance of the low molecular mass and glycoform profile associated with L-BSE, irrespective of ovine host genotype, but there was a substantially higher N-terminal antibody signal relative to the core-specific antibody, which is similar to the ratio associated with classical scrapie. The disease phenotype was maintained on experimental subpassage, but with a shortened survival time indicative of an original species barrier and subsequent adaptation. Passive surveillance approaches would be unlikely to identify such cases as TSE suspects, but current statutory active screening methods would be capable of detecting such cases and classifying them as unusual and requiring further investigation if they were to occur in the field.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-016-0394-1) contains supplementary material, which is available to authorized users.

Highlights

The transmissible spongiform encephalopathies (TSE), fatal neurodegenerative diseases of animals, have been recognised for nearly three hundred years
Despite similar diseases occurring in man (e.g. [1]) the animal TSE were not regarded as zoonotic until the emergence in 1996 of variant Creutzfeldt-Jakob Disease, linked to bovine spongiform encephalopathy (BSE) [2,3,4] which was first described in cattle in the 1980s [5]
It was established through experimental challenge that sheep and goats were susceptible to classical BSE (C-BSE) [10, 11] and a formal component of disease surveillance currently requires the classification of all TSE positive small ruminant isolates as “BSE-like” or “non-BSE-like” [EC TSE surveillance regulations (999/2001 as amended 36/2005)]

Summary

Introduction

The transmissible spongiform encephalopathies (TSE), fatal neurodegenerative diseases of animals, have been recognised for nearly three hundred years. Since its introduction in 2001, systematic EU-wide active surveillance for TSE in cattle and small ruminants [EU reg 999/2001] has resulted in the detection of two additional forms of BSE in cattle, commonly referred to collectively as “atypical”, that affected mainly cattle eight years of age or older (for reviews see [15, 16]) These cases were characterised as different from C-BSE, and designated H-BSE and L-BSE ( referred to as bovine amyloidotic spongiform encephalopathy (BASE) [17]), based on molecular features of the disease-associated form (PrPSc) of the host PrP, or prion protein, which is the marker recognised by all current surveillance tests [18, 19]. This paper presents a study of the transmissibility and characterisation of L-BSE in sheep of various genotypes, and assesses whether the current surveillance requirements would be sufficient to detect and classify such cases if they were to occur in the field

Materials and methods

Results

Discussion