Genotype-Dependent Molecular Evolution of Sheep BSE Prions In Vitro Affects Their Zoonotic Potential [Neurobiology]

August 6th, 2014 by Kreȷciova, Z., Barria, M. A., Jones, M., Ironside, J. W., Jeffrey, M., Gonzalez, L., Head, M. W.

Prion diseases are rare fatal neurological conditions of humans and animals, one of which (variant Creutzfeldt-Jakob disease) is known to be a zoonotic form of the cattle disease bovine spongiform encephalopathy (BSE). What makes one animal prion disease zoonotic and others not, is poorly understood, but it appears to involve compatibility between the prion strain and the host prion protein sequence. Concerns have been raised that the UK sheep flock may have been exposed to BSE early in the cattle BSE epidemic and that serial BSE transmission in sheep might have resulted in adaptation of the agent, which may have come to phenotypically resemble scrapie, whilst maintaining its pathogenicity for humans. We have modelled this scenario in vitro. Extrapolation from our results suggest that if BSE were to infect sheep in the field it may, with time and in some sheep genotypes, become scrapie-like at the molecular level. However, the results also suggest that if BSE in sheep were to come to resemble scrapie, it would lose its ability to affect humans.