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Time course of prion seeding activity in cerebrospinal fluid of scrapie-infected hamsters after intratongue and intracerebral inoculations.

ABSTRACT: To assess prospects for early diagnosis of prion disease based on prion seeding activity in cerebrospinal fluid (CSF), we measured the activity over time in scrapie-infected hamsters by real-time quaking-induced conversion (RT-QuIC). After intracerebral inoculation, activity appeared in CSF within 1 day and plateaued weeks before the onset of clinical signs. However, after intratongue inoculation, activity first appeared in CSF with the onset of clinical signs, well after higher-level accumulation of seeding activity in brain.

SUBMITTER: Orru CD

PROVIDER: S-EPMC3318555 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Time course of prion seeding activity in cerebrospinal fluid of scrapie-infected hamsters after intratongue and intracerebral inoculations.

Orrù Christina D CD Hughson Andrew G AG Race Brent B Raymond Gregory J GJ Caughey Byron B

Journal of clinical microbiology 20120111 4

To assess prospects for early diagnosis of prion disease based on prion seeding activity in cerebrospinal fluid (CSF), we measured the activity over time in scrapie-infected hamsters by real-time quaking-induced conversion (RT-QuIC). After intracerebral inoculation, activity appeared in CSF within 1 day and plateaued weeks before the onset of clinical signs. However, after intratongue inoculation, activity first appeared in CSF with the onset of clinical signs, well after higher-level accumulati ...[more]

PMID: 22238438

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Project description:Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a uniformly fatal family of neurodegenerative diseases in mammals that includes chronic wasting disease (CWD) of cervids. The early and ante-mortem identification of TSE-infected individuals using conventional western blotting or immunohistochemistry (IHC) has proven difficult, as the levels of infectious prions in readily obtainable samples, including blood and bodily fluids, are typically beyond the limits of detection. The development of amplification-based seeding assays has been instrumental in the detection of low levels of infectious prions in clinical samples. In the present study, we evaluated the cerebrospinal fluid (CSF) of CWD-exposed (n=44) and naïve (n=4) deer (n=48 total) for CWD prions (PrP(d)) using two amplification assays: serial protein misfolding cyclic amplification with polytetrafluoroethylene beads (sPMCAb) and real-time quaking induced conversion (RT-QuIC) employing a truncated Syrian hamster recombinant protein substrate. Samples were evaluated blindly in parallel with appropriate positive and negative controls. Results from amplification assays were compared to one another and to obex immunohistochemistry, and were correlated to available clinical histories including CWD inoculum source (e.g. saliva, blood), genotype, survival period, and duration of clinical signs. We found that both sPMCAb and RT-QuIC were capable of amplifying CWD prions from cervid CSF, and results correlated well with one another. Prion seeding activity in either assay was observed in approximately 50% of deer with PrP(d) detected by IHC in the obex region of the brain. Important predictors of amplification included duration of clinical signs and time of first tonsil biopsy positive results, and ultimately the levels of PrP(d) identified in the obex by IHC. Based on our findings, we expect that both sPMCAb and RT-QuIC may prove to be useful detection assays for the detection of prions in CSF.

Dataset Information

Time course of prion seeding activity in cerebrospinal fluid of scrapie-infected hamsters after intratongue and intracerebral inoculations.

Publications

Time course of prion seeding activity in cerebrospinal fluid of scrapie-infected hamsters after intratongue and intracerebral inoculations.

Similar Datasets

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