Human prion protein sequence elements impede cross-species chronic wasting disease transmission.

ABSTRACT: Chronic wasting disease (CWD) is a fatal prion disease of North American deer and elk and poses an unclear risk for transmission to humans. Human exposure to CWD occurs through hunting activities and consumption of venison from prion-infected animals. Although the amino acid residues of the prion protein (PrP) that prevent or permit human CWD infection are unknown, NMR-based structural studies suggest that the β2-α2 loop (residues 165-175) may impact species barriers. Here we sought to define PrP sequence determinants that affect CWD transmission to humans. We engineered transgenic mice that express human PrP with four amino acid substitutions that result in expression of PrP with a β2-α2 loop (residues 165-175) that exactly matches that of elk PrP. Compared with transgenic mice expressing

SUBMITTER: Kurt TD 

PROVIDER: S-EPMC4396485 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature