Resistance of Bovine Spongiform Encephalopathy (BSE) Prions to Inactivation

Kurt Giles,David Peretz,Stanley B Prusiner,David V Glidden,Stephen J Dearmond,Rose Seoanes,Robyn Beckwith,David Westaway

doi:10.1371/journal.ppat.1000206

Abstract

Distinct prion strains often exhibit different incubation periods and patterns of neuropathological lesions. Strain characteristics are generally retained upon intraspecies transmission, but may change on transmission to another species. We investigated the inactivation of two related prions strains: BSE prions from cattle and mouse-passaged BSE prions, termed 301V. Inactivation was manipulated by exposure to sodium dodecyl sulfate (SDS), variations in pH, and different temperatures. Infectivity was measured using transgenic mouse lines that are highly susceptible to either BSE or 301V prions. Bioassays demonstrated that BSE prions are up to 1,000-fold more resistant to inactivation than 301V prions while Western immunoblotting showed that short acidic SDS treatments reduced protease-resistant PrPSc from BSE prions and 301V prions at similar rates. Our findings argue that despite being derived from BSE prions, mouse 301V prions are not necessarily a reliable model for cattle BSE prions. Extending these comparisons to human sporadic Creutzfeldt-Jakob disease and hamster Sc237 prions, we found that BSE prions were 10- and 106-fold more resistant to inactivation, respectively. Our studies contend that any prion inactivation procedures must be validated by bioassay against the prion strain for which they are intended to be used.

Highlights

Prions are proteinaceous infectious particles that cause invariably fatal neurodegenerative diseases, including Creutzfeldt-Jakob disease (CJD) and kuru in humans, bovine spongiform encephalopathy (BSE), chronic wasting disease (CWD) in deer and elk, and scrapie in sheep and goats
Prion strains have unique electrophoretic characteristics Western immunoblotting of the four prion strains in this study revealed distinct electrophoretic profiles
While unglycosylated PrPSc of BSE migrated to 19 kDa (Figure 1A, lane 1), those of 301V, sCJD, and Sc237 had a molecular mass of 21 kDa (Figure 1A, lanes 2–4)

Summary

Introduction

Prions are proteinaceous infectious particles that cause invariably fatal neurodegenerative diseases, including Creutzfeldt-Jakob disease (CJD) and kuru in humans, bovine spongiform encephalopathy (BSE), chronic wasting disease (CWD) in deer and elk, and scrapie in sheep and goats. The only known component of the prion is an alternatively folded isoform, denoted PrPSc, of the prion protein (PrP). The PrPSc isoform is derived from the normal, cellular PrP, denoted PrPC, through a poorly understood process. Accumulation of PrPSc in the central nervous system results in spongiform changes and death. Strain characteristics are generally retained upon intraspecies transmission, but may change on transmission to another species [1,2,3,4]. The biological properties of prion strains were thought to be encoded by a nucleic acid [5] but none was found. Data from numerous studies offer convincing evidence that strain-specified information is enciphered in the conformation of PrPSc [3,6,7,8,9,10,11]

Methods

Results

Conclusion