Location: Animal Disease ResearchTitle: PrP-res in placental tissue following experimental transmission of atypical scrapie in ARR/ARR sheep is not infectious by Tg338 mouse bioassay
|PIEL III, ROBERT|
|MCELLIOTT, VALERIE - UNIVERSITY OF GEORGIA|
|STANTON, JAMES - UNIVERSITY OF GEORGIA|
|ZHUANG, DONGYUE - RETIRED ARS EMPLOYEE|
|MADSEN-BOUTERSE, SALLY - WASHINGTON STATE UNIVERSITY|
|HARRINGTON, ROBERT - RETIRED ARS EMPLOYEE|
Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/4/2022
Publication Date: 1/21/2022
Citation: Piel III, R., McElliott, V.R., Stanton, J.B., Zhuang, D., Madsen-Bouterse, S.A., Hamburg, L.K., Harrington, R.D., Schneider, D.A. 2022. PrP-res in placental tissue following experimental transmission of atypical scrapie in ARR/ARR sheep is not infectious by Tg338 mouse bioassay. PLoS ONE. 17(1). Article e0262766. https://doi.org/10.1371/journal.pone.0262766.
Interpretive Summary: Transmissible spongiform encephalopathies or prion diseases in sheep and goats are classified into two main categories: classical scrapie and Nor98-like/atypical scrapie. Classical scrapie is naturally transmissible and, along with surveillance and depopulation, breeding programs selecting for genetic resistance have been a major strategy for the control of classical scrapie in domestic ruminants. Nor98-like scrapie is generally considered non-transmissible in natural conditions and is currently exempt from control measures. Genotypes that confer resistance to classical scrapie remain susceptible to Nor98-like scrapie. ARR/ARR is a primary genotype target for resistance breeding programs and represents an increasing proportion of domestic sheep in the US. This study reports the experimental transmission of Nor98-like scrapie between ARR/ARR sheep, examines the pattern of disease in the recipient animals, and evaluates the potential for natural transmission from the recipient ewes to lambs. Inoculation of breeding ewes with Nor98-like scrapie was successful. Surprisingly, some protein with characteristics similar to prions was observed to accumulate in the placentas as recipient ewes aged; however, this material was determined to be non-infectious in a transgenic mouse model susceptible to scrapie.
Technical Abstract: Nor98-like atypical scrapie, isolated from a US sheep with the classical scrapie resistant ARR/ARR genotype, 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 broadly consistent with Nor98-like scrapie, including characteristic patterns of PrP-Sc 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 PrP-res, particularly as the animals aged. These tissues 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.