Passage of scrapie to deer results in a new phenotype upon return passage to sheep

Authors: Greenlee, Justin; Kokemuller, Robyn; MOORE, SARAH - Orise Fellow; WEST GREENLEE, N - Iowa State University

Submitted to: Prion
Publication Type: Abstract Only
Publication Acceptance Date: 3/15/2017
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Aims: We previously demonstrated that scrapie has a 100% attack rate in white-tailed deer after either intracranial or oral inoculation. Samples from deer that developed scrapie had two different western blot patterns: samples derived from cerebrum had a banding pattern similar to the scrapie inoculum, but samples from brainstem had a banding pattern similar to CWD. In contrast, transmission of CWD from white-tailed deer to sheep by the intracranial route has a low attack rate and to-date oronasal exposure has been unsuccessful. The purpose of this study was to determine if sheep are susceptible to oronasal exposure of the scrapie agent derived from white-tailed deer. Methods: At approximately 5 months of age, Suffolk sheep of various PRNP genotypes were challenged by the oronasal route with 10% brain homogenate derived from either the cerebrum or the brainstem of scrapie-affected deer. Genotypes represented in each inoculation group were VV136RR154QQ171 (n=2), AA136RR154QQ171 (n=2), and AV136RR154QR171 (n=1). After inoculation, sheep were observed daily for clinical signs. Upon development of clinical signs, sheep were killed with an overdose of pentobarbital sodium and necropsied. Tissue samples were tested for the presence of PrPSc by EIA, western blot, and immunohistochemistry (IHC). The No. 13-7 scrapie inoculum used for the deer has a mean incubation period of 20.1 months in sheep with the AA136RR154QQ171 genotype and 26.7 months in sheep with the VV136RR154QQ171 genotype. Results: Sheep inoculated oronasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum from the cerebrum that had a scrapie-like profile. The first sheep to develop clinical signs at approximately 29 months post inoculation had the VV136RR154QQ171 genotype. Eventually sheep of the AA136RR154QQ171 genotype developed clinical signs, but at a mean incubation of 52 months. At 62 months post-inoculation, none of the sheep inoculated with material from the deer brainstem have developed clinical disease. Conclusions: The No. 13-7 inoculum used in the original deer experiment readily infects white-tailed deer and sheep of various genotypes by the oronasal route. When inoculum is made from different brain regions of No 13-7 scrapie-infected deer from either cerebrum with a scrapie-like western blot pattern or brainstem with a CWD-like western blot pattern, sheep with the VV136RR154QQ171 genotype are the first to develop clinical signs. This is in contrast to the original No. 13-7 inoculum that has a faster incubation period in sheep with the AA136RR154QQ171 genotype. Similar to experiments conducted with CWD, sheep oronasally inoculated with brainstem material from deer with a CWD-like molecular profile have no evidence of disease after 62 months of incubation. While scrapie is not known to occur in free-ranging populations of white-tailed deer, experimental cases are difficult to differentiate from CWD. This work raises the potential concern that scrapie infected deer could serve as a confounding factor to scrapie eradication programs as scrapie from deer seems to be transmissible to sheep by the oronasal route.