Second passage of chronic wasting disease of mule deer to sheep by intracranial inoculation compared to classical scrapie

The origin of chronic wasting disease (CWD) in cervids is unclear. One hypothesis suggests that CWD originated from scrapie in sheep. We compared the disease phenotype of sheep-adapted CWD to classical scrapie in sheep. We inoculated sheep intracranially with brain homogenate from first-passage mule deer CWD in sheep (sCWD^md). The attack rate in second-passage sheep was 100% (12 of 12). Sheep had prominent lymphoid accumulations of PrP^Sc reminiscent of classical scrapie. The pattern and distribution of PrP^Sc in the brains of sheep with CWD^md was similar to scrapie strain 13-7 but different from scrapie strain x124. The western blot glycoprofiles of sCWD^md were indistinguishable from scrapie strain 13-7; however, independent of sheep genotype, glycoprofiles of sCWD^md were different than x124. When sheep genotypes were evaluated individually, there was considerable overlap in the glycoprofiles that precluded significant discrimination between sheep CWD and scrapie strains. Our data suggest that the phenotype of CWD in sheep is indistinguishable from some strains of scrapie in sheep. Given our results, current detection techniques would be unlikely to distinguish CWD in sheep from scrapie in sheep if cross-species transmission occurred naturally. It is unknown if sheep are naturally vulnerable to CWD; however, the susceptibility of sheep after intracranial inoculation and lymphoid accumulation indicates that the species barrier is not absolute.