Our findings demonstrate that cervid PrPSc, upon strain adaptation by serial passages in vitro or in cervid transgenic mice, is capable of converting human PrPC to produce PrPSc with unique biochemical properties, likely representing a new human prion strain. The newly generated CWD-huPrPSc material has been inoculated into transgenic mice expressing human PrP to study infectivity and disease phenotype and this data will be published elsewhere.

Today the view is that species barrier is mostly controlled by the degree of similarity on the sequence of the prion protein between the host and the infectious material (4). In our study we show that the strain and moreover the stabilization of the strain plays a major role in the inter-species transmission. In our system there is no change on the protein sequence, but yet strain adaptation results in a complete change on prion transmissibility with potentially dramatic consequences. Therefore, our findings lead to a new view of the species barrier that should not be seen as a static process, but rather a dynamic biological phenomenon that can change over time when prion strains mature and evolve. It remains to be investigated if other species barriers also change upon progressive strain adaptation of other prion forms (e.g. the sheep/human barrier).

Our results have far-reaching implications for human health, since they indicate that cervid PrPSc can trigger the conversion of human PrPC into PrPSc, suggesting that CWD might be infectious to humans. Interestingly our findings suggest that unstable strains from CWD affected animals might not be a problem for humans, but upon strain stabilization by successive passages in the wild, this disease might become progressively more transmissible to man.