Bovine spongiform encephalopathy induces misfolding of alleged prion-resistant species cellular prion protein without altering its pathobiological features.

Abstract

Bovine spongiform encephalopathy (BSE) prions were responsible for an unforeseen epizootic in cattle which had a vast social, economic, and public health impact. This was primarily because BSE prions were found to be transmissible to humans. Other species were also susceptible to BSE either by natural infection (e.g., felids, caprids) or in experimental settings (e.g., sheep, mice). However, certain species closely related to humans, such as canids and leporids, were apparently resistant to BSE. In vitro prion amplification techniques (saPMCA) were used to successfully misfold the cellular prion protein (PrP(c)) of these allegedly resistant species into a BSE-type prion protein. The biochemical and biological properties of the new prions generated in vitro after seeding rabbit and dog brain homogenates with classical BSE were studied. Pathobiological features of the resultant prion strains were determined after their inoculation into transgenic mice expressing bovine and human PrP(C). Strain characteristics of the in vitro-adapted rabbit and dog BSE agent remained invariable with respect to the original cattle BSE prion, suggesting that the naturally low susceptibility of rabbits and dogs to prion infections should not alter their zoonotic potential if these animals became infected with BSE. This study provides a sound basis for risk assessment regarding prion diseases in purportedly resistant species.

• Authors: Enric Vidal, Natalia Fernández-Borges, Belén Pintado, Montserrat Ordóñez, Mercedes Márquez, Dolors Fondevila, Juan María Torres, Martí Pumarola, Joaquín Castilla
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 33 Issue 18 Pg. 7778-86 (May 01 2013) ISSN: 1529-2401 [Electronic] United States
• PMID: 23637170 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Prions

Topics

• Animals
• Brain (metabolism, pathology)
• Cattle
• Disease Models, Animal
• Disease Susceptibility
• Dogs
• Encephalopathy, Bovine Spongiform (metabolism, mortality, transmission)
• Humans
• Mice
• Mice, Transgenic
• Nucleic Acid Amplification Techniques (methods)
• Prions (metabolism)
• Proteostasis Deficiencies (etiology, mortality, pathology)
• Rabbits
• Species Specificity
• Survival Analysis