Association between incubation time and genotype in sheep experimentally inoculated with scrapie-positive brain homogenate

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Abstract
Objective—To compare incubation time and clinical signs of scrapie in codon 136/171 alanine-valine/gluta-mine-glutamine (AVQQ) experimentally inoculated sheep with that in sheep with the more common 136/171 AAQQ genotype. Animals—60 Suffolk sheep. Procedure—Twenty-seven 171 QQ ewes purchased from 2 private flocks were bred with a 171 QQ Suffolk ram before being inoculated with a 20% solution of scrapie-positive brain homogenate (5 mL, PO) from sheep containing genotypes 136/154/171 AA/argi-nine-arginine (RR)/QQ, AVRRQQ, and VVRRQQ that had died of scrapie. Ewes had 33 lambs, which were inoculated in the same manner on the day of birth. Results—All 16 genotype 136/154/171 AVRRQQ sheep that died of scrapie were 9 to 11 months of age; clinical signs lasted 1 day to 3 weeks with no wasting and only mild pruritus. The first AARRQQ sheep died with typical clinical signs of scrapie 27 months after inoculation, and 14 were still alive 37 to 42 months after inoculation. The 136/171 AVQQ sheep had minimal accumulation of modified cellular protein (PrPSC) as determined by immunohistochemical (IHC) staining within affected cells; thus the severity of clinical signs and time of death were not associated with brain lesions or the amount of PrPSC in brain tissue of 136/154/171 AVRRQQ sheep as determined by IHC staining. Conclusions and Clinical Relevance—The rapid incubation time may have been influenced by the codon 136 genotype, a new unreported valine (V)-dependent strain of scrapie similar to strain SSBP/1, or the inoculum may have contained a traditional strain and a V-dependent or SSBP/1-like strain of scrapie.