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Updated: Aug 23, 2026
Assessing Transmissible Spongiform Encephalopathy Species Barriers with an In Vitro Prion Protein Conversion Assay
Published on: March 10, 2015
Characterization of two distinct prion strains derived from bovine spongiform encephalopathy transmissions to inbred
Sarah E Lloyd1, Jacqueline M Linehan1, Melanie Desbruslais1
1MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, London WC1N 3BG, UK.
Abstract:
Distinct prion strains can be distinguished by differences in incubation period, neuropathology and biochemical properties of disease-associated prion protein (PrP(Sc)) in inoculated mice. Reliable comparisons of mouse prion strain properties can only be achieved after passage in genetically identical mice, as host prion protein sequence and genetic background are known to modulate prion disease phenotypes. While multiple prion strains have been identified in sheep scrapie and Creutzfeldt-Jakob disease, bovine spongiform encephalopathy (BSE) is thought to be caused by a single prion strain. Primary passage of BSE prions to different lines of inbred mice resulted in the propagation of two distinct PrP(Sc) types, suggesting that two prion strains may have been isolated. To investigate this further, these isolates were subpassaged in a single line of inbred mice (SJL) and it was confirmed that two distinct prion strains had been identified. MRC1 was characterized by a short incubation time (110+/-3 days), a mono-glycosylated-dominant PrP(Sc) type and a generalized diffuse pattern of PrP-immunoreactive deposits, while MRC2 displayed a much longer incubation time (155+/-1 days), a di-glycosylated-dominant PrP(Sc) type and a distinct pattern of PrP-immunoreactive deposits and neuronal loss. These data indicate a crucial involvement of the host genome in modulating prion strain selection and propagation in mice. It is possible that multiple disease phenotypes may also be possible in BSE prion infection in humans and other animals.
Insights
Bovine spongiform encephalopathy (BSE) prions, initially thought to be a single strain, were found to comprise two distinct strains (MRC1 and MRC2) in mice. Host genetics influence prion strain selection and propagation, suggesting potential strain diversity in BSE infections.
Area of Science:
- Neuroscience
- Molecular Biology
- Veterinary Medicine
Background:
- Prion strains are differentiated by incubation period, neuropathology, and PrP(Sc) biochemical properties.
- Host genetic background significantly influences prion disease phenotypes.
- Bovine spongiform encephalopathy (BSE) has been presumed to be caused by a single prion strain.
Purpose of the Study:
- To investigate the potential existence of multiple prion strains within BSE.
- To characterize and differentiate newly isolated BSE prion strains.
Main Methods:
- Primary passage of BSE prions into different inbred mouse lines.
- Subpassage of isolates into a single inbred mouse line (SJL).
- Analysis of incubation periods, PrP(Sc) glycosylation patterns, and neuropathology.
Main Results:
- Two distinct BSE prion strains, MRC1 and MRC2, were identified.
- MRC1 exhibited shorter incubation (110 days), mono-glycosylated PrP(Sc), and diffuse PrP deposits.
- MRC2 showed longer incubation (155 days), di-glycosylated PrP(Sc), distinct PrP deposits, and neuronal loss.
Conclusions:
- The host genome plays a critical role in selecting and propagating prion strains.
- BSE may encompass multiple strains, with potential implications for human and animal infections.
- This study confirms the existence of distinct BSE prion strains and highlights host modulation.
