Histopathological Studies of “CH1641-Like” Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)

Anna Bencsik,Thierry Baron,Andrew Francis Hill

doi:10.1371/journal.pone.0022105

Anna Bencsik, Thierry Baron + Show 1 more

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https://doi.org/10.1371/journal.pone.0022105

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Abstract

The possibility of the agent causing bovine spongiform encephalopathy (BSE) infecting small ruminants is of serious concern for human health. Among scrapie cases, the CH1641 source in particular appears to have certain biochemical properties similar to the BSE strain. In France, several natural scrapie cases were identified as “CH1641-like” natural scrapie isolates in sheep and goats. The Tg(OvPrP4) mouse line expressing the ovine prion protein is a sensitive model for studying and identifying strains of agents responsible for scrapie and BSE. This model is also very useful when studying specific scrapie source CH1641, known to be not transmissible to wild-type mice despite the similarity of some of its biochemical properties to those of the BSE strain. As it is important to be able to fully distinguish CH1641 from BSE, we herein report the histopathological data from CH1641 scrapie transmission experiments compared to specific cases of “CH1641-like” natural scrapie isolates in sheep, murine scrapie strains and BSE. In addition to the conventional vacuolar lesion profile approach and PrPd brain mappings, an innovative differential PET-blot analysis was introduced to classify the different strains of agent and revealed the first direct concordance between ways of grouping strains on the basis of PrPd biochemical characteristics.

Highlights

Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative disorders that include Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats and chronic wasting disease in mule deer
Because a relationship has been established between the variant form of Creutzfeldt-Jakob disease in humans and the BSE agent infecting cattle [4,5], it is crucial to recognize the different types of infectious agents responsible for TSEs in order to secure public health
Transmission of ‘‘CH1641-like’’ natural scrapie cases The new data presented here allow us to complete the study for which the biochemical data have previously been reported [6,18]

Summary

Introduction

Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative disorders that include Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats and chronic wasting disease in mule deer. It is admitted that PrPc is converted into an abnormal protease-resistant scrapie prion protein (PrPsc, Sc for scrapie associated/PrPres, res for protease resistant), a cell-surface sialoglycoprotein with a concentrated ßsheet conformation, that accumulates in the diseased brain [1]. An immunohistochemical ‘‘peptide mapping’’ method has proven valuable for distinguishing strains in the brain and lymphoid tissue of natural hosts [13] These methods have been used to investigate possible transmission of the BSE agent under natural conditions to sheep and goats [7,8,10,12,14,15,16] and, intriguingly, revealed a few cases of TSEs in sheep that showed partial similarities to experimental ovine BSE. Molecular characterization using the immunohistochemical ‘‘peptide mapping’’ method was helpful in distinguishing these isolates—both experimental (CH1641) and natural (O100 and O104)—from BSE [20]

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