NR AOUB
AU Hill,A.F.; Linehan,J.; Desbruslais,M.; Joiner,S.; Brandner,S.; Wadsworth,J.D.F.; Collinge,J.
TI Prion infectivity in mice subclinically affected with hamster prions reveals altered pathogenicity upon multiple passages through different hosts
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - PG-22
PT Konferenz-Poster
AB Transmission of prions between different mammalian species is thought to be limited by a "species barrier", which are traditionally measured by the appearance of clinical disease in inoculated animals. We have examined the species barrier between hamsters and mice using a strain of hamster prions (Sc237) thought to be nonpathogenic to conventional mice. Prion replication occurs to high levels in wild-type mice challenged with Sc237 hamster prions without causing clinical disease. Neuropathological, molecular and passage studies reveal the presence of subclinical prion infection in such animals with high prion titres in brain. The infectivity propagated in these clinically normal mice are pathogenic to both hamsters and mice, suggesting the generation of a new prion strain from the original hamster passaged Sc237 prions. We have performed further passages from mice and hamsters infected with material from the Sc237 inoculated subclinical mice. Infectivity derived from the Sc237 inoculated mice serially passaged through further mice retains pathogenicity for both mice and hamsters with 100% of animals succumbing to clinical disease with shortened incubation periods. However, we find that infectivity derived from subclinical Sc237 inoculated mice serially passaged in hamsters retains high pathogenicity only for hamsters, with an attack rate of approximately 50% when bioassayed in further mice. The demonstration that subclinical forms of prion infection can exist in these models has important public health implications, both with respect to iatrogenic transmission from apparently healthy humans and dietary exposure to cattle and other species exposed to BSE prions. That the pathogenicity of a prion strain thought to be pathogenic to a single host can be altered following multiple passages in two species also has implications for how barriers to prion infection are measured and assessed.
IN Die Autoren inokulierten Mäuse mit Hirngewebe von Hamstern, die mit dem Hamster-Scrapie-Stamm Sc237 infiziert waren. Wie üblich erkrankten die Mäuse nicht, aber ihre Gehirne erwiesen sich in Empfängermäusen und in Empfängerhamstern als infektiös. Nach mehreren Passagen in Mäusen blieb dieser Scrapiestamm infektiös für Mäuse und Hamster, während Hamsterhirn trotz der einmaligen Passage durch Mäuse wenig infektiös blieb.
AD J. Linehan, M. Desbruslais, S. Joiner, S. Brandner, J.D. Wadsworth, J. Collinge, MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, UK; A.F. Hill, Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, Australia
SP englisch
PO Deutschland