Classical Bovine Spongiform Encephalopathy by Transmission of H-Type Prion in Homologous Prion Protein Context

Juan-María Torres

doi:10.3201/eid1709.101403

Abstract

Bovine spongiform encephalopathy (BSE) and BSE-related disorders have been associated with a single major prion strain. Recently, 2 atypical, presumably sporadic forms of BSE have been associated with 2 distinct prion strains that are characterized mainly by distinct Western blot profiles of abnormal protease-resistant prion protein (PrPres), named high-type (BSE-H) and low-type (BSE-L), that also differed from classical BSE. We characterized 5 atypical BSE-H isolates by analyzing their molecular and neuropathologic properties during transmission in transgenic mice expressing homologous bovine prion protein. Unexpectedly, in several inoculated animals, strain features emerged that were highly similar to those of classical BSE agent. These findings demonstrate the capability of an atypical bovine prion to acquire classical BSE-like properties during propagation in a homologous bovine prion protein context and support the view that the epidemic BSE agent could have originated from such a cattle prion.

Highlights

Bovine spongiform encephalopathy (BSE) and BSErelated disorders have been associated with a single major prion strain
Multiple agent strains have been identified in sheep scrapie [1,2] and human Creutzfeldt-Jakob disease (CJD) [3,4], early evidence showed that BSE was caused by a single major strain [5,6] with the ability to efficiently cross the species barriers and showing stable features even when transmitted to other species
We show that the transmission of atypical BSE-H isolates in transgenic mice expressing homologous bovine prion protein (PrP) led to emergence of a clearly distinct prion with strain features similar to those of the BSE-C agent and that such similarities were maintained on subsequent passages

Summary

Introduction

Bovine spongiform encephalopathy (BSE) and BSErelated disorders have been associated with a single major prion strain. We characterized 5 atypical BSE-H isolates by analyzing their molecular and neuropathologic properties during transmission in transgenic mice expressing homologous bovine prion protein. In several inoculated animals, strain features emerged that were highly similar to those of classical BSE agent. Transmissible spongiform encephalopathies, or prion diseases, are a group of neurodegenerative disorders that include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and goats, and bovine spongiform encephalopaty (BSE) in cattle. Several authors reported that BSE and vCJD prions share similar strain-specific features, including a unique PrPres molecular signature [6,9,10], after transmission to mice or macaques,. Classical BSE and H-Type Prion or from a spontaneous bovine prion disease analogous to sporadic forms of CJD in human [15] or even from human transmissible spongiform encephalopathy [16]

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Conclusion