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Detection of water-soluble disease-associated PrP species in blood and brain of scrapie-infected hamster

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Abstract

The high-speed supernatant (SHS) of scrapie-infected hamster brain homogenate contains a soluble infectivity similar to that of the plasma that escapes leukodepletion and can transmit prion infection. This recent finding highlights the fact that soluble prion infectivity could be relevant for prion disease propagation and progression. PrPSc is essential in prion disease pathogenesis, but little to nothing is known about the PrPSc species that may be associated with this form of prion infectivity. Scrapie-infected hamster plasma and SHS were subjected to biochemical analysis, and the results demonstrate for the first time that soluble infectivity is associated with a water-soluble PrPSc species with substantially different properties from classical PrPSc, the concentration of which seems to correlate with the magnitude and efficiency of the soluble infectivity. Such characteristics suggest that this species might represent the soluble prion agent itself or its vehicle, highlighting the need to adequately revise the strategies involved in prion removal, diagnosis, and therapy.

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Abbreviations

TSE:

Transmissible spongiform encephalopathy

PrPC :

Cellular prion protein

PrPSc :

Abnormal prion protein

PrP27-30:

27- to 30-kDa fragment of PrPSc

SHS :

High-speed supernatant

SLS :

Low-speed supernatant

PHS :

High-speed pellet

DELFIA:

Dissociation-enhanced fluoroimmunoassay

PK:

Proteinase-K

TRF:

Time-resolved fluorescence

ws-PrPSc :

Water-soluble PrPSc

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Acknowledgments

I am grateful to Vito Angelo Berardi for preparing SHS fractions. I thank also Angelina Valanzano for blood collection and Nicola Bellizzi, Maurizio Bonanno, Ivano Itro, and Elfino Laconi for the animal care and assistance in the blood collection. I also thank Mrs. Cinzia Gasparrini for editorial assistance.

Conflict of interest

The author declares that she has no conflict of interest.

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  1. Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy

    Hanin Abdel-Haq

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Correspondence to Hanin Abdel-Haq.

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Abdel-Haq, H. Detection of water-soluble disease-associated PrP species in blood and brain of scrapie-infected hamster. Arch Virol 160, 2219–2229 (2015). https://doi.org/10.1007/s00705-015-2487-y

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