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


Autoři: Simone Hornemann aff001;  Petra Schwarz aff001;  Elisabeth J. Rushing aff001;  Michael D. Connolly aff003;  Ronald N. Zuckermann aff003;  Alice Y. Yam aff002;  Adriano Aguzzi aff001
Působiště autorů: Institute of Neuropathology, University of Zurich, Zurich, Switzerland aff001;  Novartis Vaccines and Diagnostics Inc., Emeryville, California, United States of America aff002;  Biological Nanostructures Facility, The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America aff003
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0216013

Souhrn

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.

Klíčová slova:

Biology and life sciences – Organisms – Eukaryota – Animals – Vertebrates – Amniotes – Mammals – Rodents – Hamsters – Zoology – Animal diseases – Animal prion diseases – Anatomy – Body fluids – Blood – Blood plasma – Physiology – Medicine and health sciences – Infectious diseases – Prion diseases – Creutzfeldt-Jakob disease – Zoonoses – Neurology – Neurodegenerative diseases – Research and analysis methods – Specimen preparation and treatment – Staining – Group-specific staining – Hematoxylin staining


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