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Enhanced detection of prion infectivity from blood by preanalytical enrichment with peptoid-conjugated beads


Hornemann, Simone; Schwarz, Petra; Rushing, Elisabeth J; Connolly, Michael D; Zuckermann, Ronald N; Yam, Alice Y; Aguzzi, Adriano (2019). Enhanced detection of prion infectivity from blood by preanalytical enrichment with peptoid-conjugated beads. PLoS ONE, 14(9):e0216013.

Abstract

Prions cause transmissible infectious diseases in humans and animals and have been found to be transmissible by blood transfusion even in the presymptomatic stage. However, the concentration of prions in body fluids such as blood and urine is extremely low; therefore, direct diagnostic tests on such specimens often yield false-negative results. Quantitative preanalytical prion enrichment may significantly improve the sensitivity of prion assays by concentrating trace amounts of prions from large volumes of body fluids. Here, we show that beads conjugated to positively charged peptoids not only captured PrP aggregates from plasma of prion-infected hamsters, but also adsorbed prion infectivity in both the symptomatic and preclinical stages of the disease. Bead absorbed prion infectivity efficiently transmitted disease to transgenic indicator mice. We found that the readout of the peptoid-based misfolded protein assay (MPA) correlates closely with prion infectivity in vivo, thereby validating the MPA as a simple, quantitative, and sensitive surrogate indicator of the presence of prions. The reliable and sensitive detection of prions in plasma will enable a wide variety of applications in basic prion research and diagnostics.

Abstract

Prions cause transmissible infectious diseases in humans and animals and have been found to be transmissible by blood transfusion even in the presymptomatic stage. However, the concentration of prions in body fluids such as blood and urine is extremely low; therefore, direct diagnostic tests on such specimens often yield false-negative results. Quantitative preanalytical prion enrichment may significantly improve the sensitivity of prion assays by concentrating trace amounts of prions from large volumes of body fluids. Here, we show that beads conjugated to positively charged peptoids not only captured PrP aggregates from plasma of prion-infected hamsters, but also adsorbed prion infectivity in both the symptomatic and preclinical stages of the disease. Bead absorbed prion infectivity efficiently transmitted disease to transgenic indicator mice. We found that the readout of the peptoid-based misfolded protein assay (MPA) correlates closely with prion infectivity in vivo, thereby validating the MPA as a simple, quantitative, and sensitive surrogate indicator of the presence of prions. The reliable and sensitive detection of prions in plasma will enable a wide variety of applications in basic prion research and diagnostics.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > General Biochemistry, Genetics and Molecular Biology
Life Sciences > General Agricultural and Biological Sciences
Health Sciences > Multidisciplinary
Uncontrolled Keywords:General Biochemistry, Genetics and Molecular Biology, General Agricultural and Biological Sciences, General Medicine
Language:English
Date:12 September 2019
Deposited On:20 Dec 2019 13:39
Last Modified:22 Apr 2020 21:38
Publisher:Public Library of Science (PLoS)
ISSN:1932-6203
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1371/journal.pone.0216013
Project Information:
  • : FunderH2020
  • : Grant ID670958
  • : Project TitleFunction and malfunction of the prion protein
  • : FunderSNSF
  • : Grant ID31003A_179040
  • : Project TitleThe prion protein in health and disease
  • : FunderCRPP
  • : Grant ID
  • : Project TitleSmall RNAs
  • : FunderCRPP
  • : Grant ID
  • : Project TitleHHLD
  • : FunderSystemsX.ch
  • : Grant ID2014/260
  • : Project TitlePrionX
  • : FunderSystemsX.ch
  • : Grant ID2015/320
  • : Project TitleSynucleiX
  • : FunderGelu Foundation
  • : Grant ID
  • : Project TitleCRYSTAL&HITS

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