TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Location: Virus and Prion Research Unit
Title: Strain typing of U.S. scrapie strains using a panel of inbred mice
Submitted to: American College of Veterinary Pathologists Meeting
Publication Type: Abstract Only
Publication Acceptance Date: July 15, 2008
Publication Date: November 15, 2009
Citation: Greenlee, J.J., Kunkle, R.A., Nicholson, E.M., Hamir, A.N., Bulgin, M.S., Richt, J. 2009. Strain Typing of U.S. Scrapie Strains Using a Panel of Inbred Mice [abstract]. American College of Veterinary Pathologists. Paper No. 121. p. 762.
Prion strains may vary in their ability to transmit to humans and animals. Few experimental studies have been done to provide evidence of differences between U.S. strains of scrapie, which can be distinguished by incubation times in inbred mice, microscopic lesions, immunoreactivity to various antibodies, or molecular profile (electrophoretic mobility and glycoform ratio). Recent work on two U.S. isolates of sheep scrapie supports that at least two distinct strains exist based on differences in incubation time and genotype of sheep affected. One isolate (No. 13-7) inoculated intracerebrally caused scrapie in sheep AA at codon 136 (AA136) and QQ at codon 171 (QQ171) of the prion protein in an average of 19 months post-inoculation (PI) whereas a second isolate (No. x124) caused disease in less than 12 months after oral inoculation in AV136/QQ171 sheep. Striking differences were evident when further strain analysis was done in R111, VM, C57Bl6, and C57Bl6xVM (F1) mice. No. 13-7 did not induce disease in any mouse strain at any time post-inoculation (PI) nor were brain tissues positive by western blot (WB). Positive WB results were obtained from mice inoculated with isolate No. x124 starting at day 380 PI. Incubation times averaged 508, 559, 601, and 633 days PI for RIII, C57Bl6, VM, and F1 mice, respectively. Further passage will be required to characterize these scrapie strains in mice. This work provides evidence that multiple scrapie strains exist in U.S. sheep.