Different transmissible properties of CWD prions from North America and Northern Europe in cervidized gene-targeted mice

Authors: DEFRANCO, JOSEPH - Colorado State University; KIM, SEHUN - Colorado State University; ATKINSON, ZOE - Colorado State University; CROWELL, JENNA - Colorado State University; HALL, MARY - Colorado State University; BODROGI, HANNAH - Colorado State University; Bian, Jifeng; BENESTAD, SYLVIE - Colorado State University; TELLING, GLENN - Colorado State University

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 5/19/2025
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Chronic wasting disease (CWD) from North America (NA) transmits through multiple infection routes in the natural host. However, less is known about the transmissible properties of newly emergent Nordic CWD in reindeer (R-NO) and moose (M-NO). Our group developed gene-targeted (Gt) mouse models that express the cervid prion protein (PrP) under the endogenous regulatory elements of the murine Prnp promotor. Consequently, these Gt mice express exogenous PrP at physiological levels in the periphery and replicate NA CWD in several extraneural tissues. Utilizing these mice, we found that while intraperitoneal and oral challenge of NA CWD retain native strain properties, intracerebral inoculations resulted in altered CWD prions producing a distinct disease outcome. These data suggest that there are tissue-specific cofactors responsible for prion strain selection, replication, and propagation. Based on these findings, we transmitted several NA CWD and NO CWD isolates by nine different routes of inoculation to our Gt models. Interestingly, while NA CWD is highly competent at transmitting by all routes of inoculation, R-NO and M-NO CWD prions are less efficient. These data further support the hypothesis that NA CWD harbor distinct strain properties from those comprising emergent R-NO and M-NO CWD isolates. These transmissible differences have major public health implications for the ongoing CWD outbreaks in Northern Europe. Moreover, these findings of variable transmission dynamics suggest that their distinct strain properties alter their capacity to replicate in peripheral compartments and bolster our previous findings of tissue-specific cofactors responsible for prion strain selection and propagation.