Biochemical characterization of prion strains in bank voles.

Laura Pirisinu,Michele Angelo Di Bari,Stefano Marcon,Claudia D'Agostino,Umberto Agrimi,Romolo Nonno

doi:10.3390/pathogens2030446

Abstract

Prions exist as different strains exhibiting distinct disease phenotypes. Currently, the identification of prion strains is still based on biological strain typing in rodents. However, it has been shown that prion strains may be associated with distinct PrPSc biochemical types. Taking advantage of the availability of several prion strains adapted to a novel rodent model, the bank vole, we investigated if any prion strain was actually associated with distinctive PrPSc biochemical characteristics and if it was possible to univocally identify strains through PrPSc biochemical phenotypes. We selected six different vole-adapted strains (three human-derived and three animal-derived) and analyzed PrPSc from individual voles by epitope mapping of protease resistant core of PrPSc (PrPres) and by conformational stability and solubility assay. Overall, we discriminated five out of six prion strains, while two different scrapie strains showed identical PrPSc types. Our results suggest that the biochemical strain typing approach here proposed was highly discriminative, although by itself it did not allow us to identify all prion strains analyzed.

Highlights

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are neurodegenerative disorders that afflict humans and others mammals
The bank voles are susceptible to a wide range of prion sources: human sCJD and gCJD [24,25], sheep scrapie [26,27], cattle and sheep bovine spongiform encephalopathy (BSE) [24,28], cervid Chronic Wasting
Sheep scrapie isolates SCR1, SCR10 and SCR11 [26,31] which all gave in vole the same scrapie strain, “UK85”, different from that derived from Italian scrapie isolates, It93; (vi) bovine BSE [28]

Summary

Introduction

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are neurodegenerative disorders that afflict humans and others mammals. Prion diseases may be caused by prion exposure (acquired forms), mutations in PRNP gene (genetic or hereditary forms) and sporadic events in which the source of infection has not yet been demonstrated (idiopathic or sporadic forms). They include sporadic and genetic Creutzfeldt-Jakob disease (sCJD and gCJD) in humans, scrapie in sheep and goats and bovine spongiform encephalopathy (BSE) in cattle. Prions exist as different strains that, when propagated in the same host, exhibit distinct disease phenotypes that persist upon serial transmissions [2,3]. Within the context of the protein-only hypothesis, it has been suggested that prion strain diversity is encrypted in distinct conformations of

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