Structural effects of PrP polymorphisms on intra- and interspecies prion transmission

The unpredictable recurrences of prion epidemics, their incurable lethality, and the capacity of animal prions to infect humans provide significant motivation to ascertain the parameters governing disease transmission. The unprecedented spread and uncertain zoonotic potential of chronic wasting disease, a contagious epidemic among deer, elk, and other cervids, is of particular concern. Here we demonstrate that naturally occurring primary structural differences in cervid PrPs differentially impact the efficiency of intra- and interspecies prion transmission. Our results not only deliver information about the role of primary structural variation on prion susceptibility, but also provide functional support to a mechanism in which plasticity of a tertiary structural epitope governs prion protein conversion and intra- and interspecies susceptibility to prions.