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

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.

Polymorphisms in the prion precursor functional gene but not the pseudogene are associated with susceptibility to chronic wasting disease in white-tailed deer.

Chronic wasting disease (CWD) status and PrP genotypes were determined for a group of 133 wild white-tailed deer in a 780 acre enclosure in western Nebraska, USA. Approximately half of the deer tested showed evidence of PrPd in the brainstem or lymphoid tissues. Four PRNP alleles encoding amino acid substitutions were identified, with substitutions at residues 95 (Q-->H), 96 (G-->S) or 116 (A-->G), each with serine (S) at residue 138. In addition, a processed pseudogene with two alleles encoding five or six copies of the octapeptide repeat was identified in 26 % of the deer. Both alleles encoded asparagine (N) at residue 138. The functional gene alleles sorted into five major diploid genotypes and four rare genotypes. Although all five major diploid genotypes were found in deer with CWD, unaffected deer were less likely to have the allele QGAS and more likely to have QSAS compared with CWD-affected deer. Late-stage disease (PrPd in brainstem) was noted in deer less than 1 year of age, although no single genotype was associated with this rapid neuroinvasion. Early-stage disease (PrPd distribution limited to the lymphoid system) was observed in deer estimated to be more than 5 years old, suggesting that they were infected as adults or that the incubation time might be extremely long in some individuals. The pseudogene was found in deer of all major PRNP genotypes and was not correlated with CWD status. The large number of susceptible genotypes and the possibility of adult-to-adult transmission suggest that much of the white-tailed deer population may be at risk for disease following exposure to CWD, despite the association of specific genotypes with CWD noted here.