North American and Norwegian Chronic Wasting Disease prions exhibit different potential for interspecies transmission and zoonotic risk.

Chronic wasting disease (CWD) is a rapidly spreading prion disorder affecting various species of wild and captive cervids. The risk that CWD poses to co-habiting animals or more importantly to humans is largely unknown. In this study we investigated differences in the capacity of CWD isolates obtained from six different cervid species to induce prion conversion in vitro by PMCA. We define and quantify spillover and zoonotic potential indices as the efficiency by which CWD prions sustain prion generation in vitro at expenses of normal prion proteins from various mammals and human, respectively. Our data suggest that reindeer and red deer from Norway could be the most transmissible CWD prions to other mammals, whereas North American CWD prions were more prone to generate human prions in vitro. Our results suggest that Norway and North American CWD prions correspond to different strains with distinct spillover and zoonotic potentials.