Abstract |
The pathological isoform of the prion protein ( PrP(res)) can serve as a marker for prion diseases, but more practical tests are needed for preclinical diagnosis and sensitive detection of many prion infections. Previously we showed that the quaking-induced conversion (QuIC) assay can detect sub-femtogram levels of PrP(res) in scrapie-infected hamster brain tissue and distinguish cerebral spinal fluid (CSF) samples from normal and scrapie-infected hamsters. We now report the adaptation of the QuIC reaction to prion diseases of medical and agricultural interest: human variant Creutzfeldt-Jakob disease (vCJD) and sheep scrapie. PrP(res)-positive and -negative brain homogenates from humans and sheep were discriminated within 1-2 days with a sensitivity of 10-100 fg PrP(res). More importantly, in as little as 22 h we were able to distinguish CSF samples from scrapie-infected and uninfected sheep. These results suggest the presence of prions in CSF from scrapie-infected sheep. This new method enables the relatively rapid and sensitive detection of human CJD and sheep scrapie PrP(res) and may facilitate the development of practical preclinical diagnostic and high-throughput interference tests.
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Authors | Christina D Orrú, Jason M Wilham, Andrew G Hughson, Lynne D Raymond, Kristin L McNally, Alex Bossers, Ciriaco Ligios, Byron Caughey |
Journal | Protein engineering, design & selection : PEDS
(Protein Eng Des Sel)
Vol. 22
Issue 8
Pg. 515-21
(Aug 2009)
ISSN: 1741-0134 [Electronic] England |
PMID | 19570812
(Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Prions
- Recombinant Proteins
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Topics |
- Animals
- Biological Assay
(methods)
- Brain Chemistry
- Creutzfeldt-Jakob Syndrome
(metabolism)
- Cricetinae
- Humans
- Prions
(analysis, cerebrospinal fluid, isolation & purification, metabolism)
- Recombinant Proteins
(isolation & purification, metabolism)
- Scrapie
(metabolism)
- Sheep
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