Disease phenotype of classical sheep scrapie is changed upon experimental passage through white-tailed deer

Kokemuller, Robyn D.; Moore, S. Jo; Bian, Jifeng; West Greenlee, M. Heather; Greenlee, Justin J.

doi:10.1371/journal.ppat.1011815

Disease phenotype of classical sheep scrapie is changed upon experimental passage through white-tailed deer

Journal Article · Mon Dec 04 00:00:00 EST 2023 · PLoS Pathogens

DOI:https://doi.org/10.1371/journal.ppat.1011815· OSTI ID:2469794

Kokemuller, Robyn D. ^[1]; Moore, S. Jo ^[1]; Bian, Jifeng ^[1]; West Greenlee, M. Heather ^[2]; ^[1]

US Dept. of Agriculture (USDA), Ames, IA (United States). Agricultural Research Service (ARS)
Iowa State University, Ames, IA (United States)

Prion agents occur in strains that are encoded by the structure of the misfolded prion protein (PrP^Sc). Prion strains can influence disease phenotype and the potential for interspecies transmission. Little is known about the potential transmission of prions between sheep and deer. Previously, the classical US scrapie isolate (No.13-7) had a 100% attack rate in white-tailed deer after oronasal challenge. The purpose of this study was to test the susceptibility of sheep to challenge with the scrapie agent after passage through white-tailed deer (WTD scrapie). Lambs of various prion protein genotypes were oronasally challenged with WTD scrapie. Sheep were euthanized and necropsied upon development of clinical signs or at the end of the experiment (72 months post-inoculation). Enzyme immunoassay, western blot, and immunohistochemistry demonstrated PrP^Sc in 4 of 10 sheep with the fastest incubation occurring in VRQ/VRQ sheep, which contrasts the original No.13-7 inoculum with a faster incubation in ARQ/ARQ sheep. Shorter incubation periods in VRQ/VRQ sheep than ARQ/ARQ sheep after passage through deer was suggestive of a phenotype change, so comparisons were made in ovinized mice and with sheep with known strains of classical sheep scrapie: No. 13–7 and x-124 (that has a more rapid incubation in VRQ/VRQ sheep). After mouse bioassay, the WTD scrapie and x-124 isolates have similar incubation periods and PrP^Sc conformational stability that are markedly different than the original No. 13–7 inoculum. Furthermore, brain tissues of sheep with WTD scrapie and x-124 scrapie have similar patterns of immunoreactivity that are distinct from sheep with No. 13–7 scrapie. Multiple lines of evidence suggest a phenotype switch when No. 13–7 scrapie prions are passaged through deer. This represents one example of interspecies transmission of prions resulting in the emergence or selection of new strain properties that could confound disease eradication and control efforts.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0014664

OSTI ID:: 2469794

Journal Information:: PLoS Pathogens, Journal Name: PLoS Pathogens Journal Issue: 12 Vol. 19; ISSN 1553-7374

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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