Oral inoculation of neonatal Suffolk sheep with the agent of classical scrapie results in PrPSc accumulation in sheep with the PRNP ARQ/ARQ but not the ARQ/ARR genotype

Abstract

Scrapie is a transmissible spongiform encephalopathy that can be transmitted amongst susceptible sheep. The prion protein gene (PRNP) profoundly influences the susceptibility of sheep to the scrapie agent. This study reports the failure to detect PrPSc in nervous or lymphoid tissues of Suffolk sheep of the PRNP ARQ/ARR genotype after oral inoculation with a U.S. scrapie isolate. Lambs were inoculated within the first 24h of birth with 1ml of a 10% (wt./vol.) brain homogenate derived from a clinically affected ARQ/ARQ sheep. The inoculated sheep were observed daily throughout the experiment for clinical signs suggestive of scrapie until they were necropsied at 86months post inoculation. Tissues were collected for examination by immunohistochemistry and enzyme immunoassay, but all failed to demonstrate evidence of scrapie infection. Neonatal sheep of the ARQ/ARQ genotype receiving the same inoculum developed scrapie within 24months. Lambs of the ARQ/ARR genotype that received the same inoculum by intracranial inoculation develop scrapie with a prolonged incubation period and with abnormal prion present within the central nervous system, but not peripheral lymphoid tissues. Results of this study suggest that ARQ/ARR sheep are resistant to oral infection with the scrapie isolate used even during the neonatal period.