Species Barriers in Prion Disease

Species barriers in prion diseases are defined by the difficulty that prions from one species have in triggering prion infection in a new species. The amino acid sequence of the normal host prion protein (PrPC), the available pool of exogenous abnormal and infectious prion protein (PrPSc), and the ability to establish a subclinical infection are all important determinants of prion species barriers. Mechanistically, maintenance of species barriers to prion infection is likely dependent upon the conformational diversity of the PrPSc molecules in an infectious inoculum and the potential for conformational compatibility between the exogenous PrPSc and endogenous host PrPC. However, the lack of high resolution structural information for PrPSc, the potential for host factors and posttranslational modifications to PrPC to influence species barriers, and the fact that the amino acids important in prion species barriers differ between species, makes it difficult to predict prion species barriers based on PrPC sequence alone. In vivo or in vitro experimentation in relevant models of infection remains the only way to determine species barriers to prion infection.