title: Comparison of Two US Sheep Scrapie Isolates Supports Identification as Separate Strains.
abstract: Scrapie is a naturally occurring transmissible spongiform encephalopathy of sheep and goats. There are different strains of sheep scrapie that are associated with unique molecular, transmission, and phenotype characteristics. However, in the United States, very little is known about the potential presence of scrapie strains. Scrapie strain and PRNP genotype could both affect susceptibility, potential for transmission, incubation period (IP), and control measures required for eliminating scrapie from a flock. The investigators evaluated 2 US scrapie isolates, No. 13-7 and x124, after intranasal inoculation to compare clinical signs, IPs, spongiform lesions, and patterns of PrPScdeposition in sheep with scrapie-susceptible PRNP genotypes (QQ171). After inoculation with x124, susceptibility and IP were associated with valine at codon 136 (V136) of the prion protein: VV136 sheep had short IPs (6.9 months), those in AV136 sheep were 11.9 months, and AA136 sheep did not develop scrapie. All No. 13-7 inoculated sheep developed scrapie, with IPs of 20.1 months for AA136 sheep, 22.8 months for AV136 sheep, and 26.7 months for VV136 sheep. Patterns of immunoreactivity in the brain were influenced by inoculum isolate and host genotype. Differences in PrPScprofiles versus isolate were most striking when examining brains from sheep with the VV136 genotype. Inoculation into C57BL/6 mice resulted in markedly different attack rates (90.5% for x124 and 5.9% for No. 13-7). Taken together, these data demonstrate that No. 13-7 and x124 represent 2 distinct strains of scrapie with different IPs, genotype susceptibilities, and PrPScdeposition profiles.
authors.affiliation: Virus and Prion Research Unit, National Animal Disease Center, Agricultural Research Service, US Department of Agriculture, Ames, IA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Moore
authors.affiliation: Virus and Prion Research Unit, National Animal Disease Center, Agricultural Research Service, US Department of Agriculture, Ames, IA.
authors.forename: J D
authors.initials: JD
authors.lastname: Smith
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA.
authors.forename: M H West
authors.initials: MH
authors.lastname: Greenlee
authors.affiliation: Virus and Prion Research Unit, National Animal Disease Center, Agricultural Research Service, US Department of Agriculture, Ames, IA.
authors.forename: E M
authors.initials: EM
authors.lastname: Nicholson
authors.affiliation: Virus and Prion Research Unit, National Animal Disease Center, Agricultural Research Service, US Department of Agriculture, Ames, IA.
authors.forename: J A
authors.initials: JA
authors.lastname: Richt
authors.affiliation: Virus and Prion Research Unit, National Animal Disease Center, Agricultural Research Service, US Department of Agriculture, Ames, IA justin.greenlee@ars.usda.gov.
authors.forename: J J
authors.initials: JJ
authors.lastname: Greenlee
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D005838:Genotype; D051379:Mice; D008810:Mice, Inbred C57BL; D018620:PrPSc Proteins / Q000235:genetics; D011328:Prions / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D012608:Scrapie / Q000453:epidemiology* / Q000473:pathology; D012756:Sheep; D014481:United States / Q000453:epidemiology
chemical_list: D018620:PrPSc Proteins; D011328:Prions
keywords: PRNP; PrPSc proteins; intranasal administration; prion diseases; prion protein; scrapie; sheep; transmissible spongiform encephalopathies