PrPres in placental tissue following experimental transmission of atypical scrapie in ARR/ARR sheep is not infectious by Tg338 mouse bioassay

Abstract

Nor98-like atypical scrapie is a sporadic disease that affects the central nervous system of sheep and goats that, in contrast to classical scrapie, is not generally regarded as naturally transmissible. However, infectivity has been demonstrated via bioassay not only of brain tissue but also of certain peripheral nerves, lymphoid tissues, and muscle. This study examines placental tissue, a well characterized route of natural transmission for classical scrapie. Further, this study was conducted in sheep homozygous for the classical scrapie resistant ARR genotype and is the first to characterize the transmission of Nor98-like scrapie between homozygous-ARR sheep. Nor98-like scrapie isolated from a United States ARR/ARR sheep was transmitted to four ARR/ARR ewes via intracerebral inoculation of brain homogenate. These ewes were followed and observed to 8 years of age, remained non-clinical but exhibited progression of infection that was consistent with Nor98-like scrapie, including characteristic patterns of PrPSc accumulation in the brain and a lack of accumulation in peripheral lymphoid tissues as detected by conventional methods. Immunoblots of placental tissues from the infected ewes revealed accumulation of a distinct conformation of PrPres, particularly as the animals aged; however, the placenta showed no infectivity when analyzed via ovinized mouse bioassay. Taken together, these results support a low risk for natural transmission of Nor98-like scrapie in ARR/ARR sheep.

B‐cell leukemia in an adult sheep

“…The wether described herein was part of a natural transmission study of atypical scrapie. 1 The study included four ewes initially infected with atypical scrapie by inoculation, 32 first-generation offspring, 11 second-generation offspring including this patient, and seven breeding rams. Atypical scrapie is a transmissible spongiform encephalopathy (TSE) or prion disease that primarily affects sheep and goats.…”

“…A 5‐year‐old WhiteFace Sheep wether presented for acute lethargy and inappetence. The wether was a second‐generation relative of a ewe experimentally inoculated with atypical (Nor98‐like) scrapie 1 . The inoculated ewe (the grandparent of the presenting patient) became infected with atypical scrapie but never developed clinical signs despite reaching 7 years of age.…”

“…The wether was a second-generation relative of a ewe experimentally inoculated with atypical (Nor98-like) scrapie. 1 The inoculated ewe (the grandparent of the presenting patient) became infected with atypical scrapie but never developed clinical signs despite reaching 7 years of age. First-and second-generation offspring of these ewes, including the presenting patient, were monitored for signs of scrapie up until postmortem examination; scrapie was not detected in the postmortem tissues of these descendant sheep by prion immunohistochemistry.…”