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Simplified ultrasensitive prion detection by recombinant PrP conversion with shaking

Nature Methods volume 5, pages 211–212 (2008)Cite this article

To the editor:

A key problem in managing prion diseases is the lack of a rapid, practical assay for prions (infectivity) at low-level infectious, or sub-infectious, amounts. Prion diseases involve the accumulation of a pathological, typically protease-resistant form of prion protein, termed PrPSc, which appears to propagate itself in infected hosts by inducing the conversion of its normal host-encoded precursor, PrP-sen, into additional PrPSc (refs. 1–4). In crude brain homogenates, PrPSc and infectivity can be amplified from endogenous PrP-sen during multiple rounds of intermittent sonication and serial dilution into fresh normal brain homogenate2,4. This ultrasensitive assay, termed PMCA, allows detection of ∼1 ag of PrPSc in ∼3 weeks5.

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Figure 1: QUIC reactions seeded with brain homogenates and CSF samples from normal or scrapie-affected hamsters.

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Acknowledgements

We thank G. Baron, V. Sim and L. Taubner for critical review of this manuscript. We thank K. Meade-White and B. Race (Rocky Mountain Laboratories) for the CSF samples, G. Raymond (Rocky Mountain Laboratories) for the brain tissue samples, and G. Hettrick and A. Mora for graphics assistance. This research was supported in part by the Intramural Research Program of the US National Institute of Allergy and Infectious Diseases, National Institutes of Health.

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  1. Henry A Onwubiko

    Present address: Present address: Department of Biochemistry, University of Nigeria-Nsukka, Nsukka, Enugu State, Nigeria.,

Authors and Affiliations

  1. Laboratory of Persistent Viral Diseases, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, 903 S. 4th St., Hamilton, 59840, Montana, USA

    Ryuichiro Atarashi, Jason M Wilham, Leah Christensen, Andrew G Hughson, Roger A Moore, Lisa M Johnson, Henry A Onwubiko, Suzette A Priola & Byron Caughey

  2. Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan

    Ryuichiro Atarashi

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  1. Ryuichiro Atarashi
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Competing interests

R.A., R.A.M., S.A.P. and B.C. are authors on US patent applications 60/961,364 and 61/021,865, which cover the detection of prions by seeded conversion of recombinant prion protein.

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Supplementary Figures 1–6, Supplementary Results, Supplementary Methods (PDF 840 kb)

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Atarashi, R., Wilham, J., Christensen, L. et al. Simplified ultrasensitive prion detection by recombinant PrP conversion with shaking. Nat Methods 5, 211–212 (2008). https://doi.org/10.1038/nmeth0308-211

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