Impact of Amino Acid Difference at Residue 226 in Cervid Prion Protein on Chronic Wasting Disease Outcome
Category: Research Poster
Author(s): Elizabeth Host, Xutong Shi
Presenter(s): Elizabeth Host
Mentors(s): Xutong Shi
Chronic wasting disease (CWD) is a prion disease affecting cervid species in North America since 1967. Our previous studies showed that the primary structural differences at residue 226 of deer and elk prion protein (PrP) dictates selection of distinct CWD prion strains in gene-targeted mice expressing cervid PrP. Here, by using the same platform, we characterized the CWD strain properties of farmed red deer (Cervus elaphus) in Quebec, Canada. We assessed how genetic variation in Canadian red deer and the route of inoculation impacts CWD disease phenotype, infection kinetics and prion distribution in the brain. Our results suggest that transmission of Canadian red deer CWD prions into mice expressing homozygous glutamate (EE) at 226 residue of PrP is more efficient compared to mice expressing homozygous glutamine (QQ) at the same position, and the transmission efficiency into mice expressing heterozygous EQ at the 226 residue of PrP depends on the amino acid expressed in the field isolate. Data also shows that the differences between the intracerebral and intraperitoneal inoculation routes impact prion strain biochemical and neuropathological properties. These findings suggest that both the amino acid variation at residue 226 of PrP and the different inoculation routes impact prion strain properties. Our results provide insight into the mechanisms governing prion strain selection and adaptation.