Bank Vole Prion Protein As an Apparently Universal Substrate for RT-QuIC-Based Detection and Discrimination of Prion Strains

Christina D. Orrú, Bradley R. Groveman, Lynne D. Raymond, Andrew G. Hughson, Romolo Nonno, Wenquan Zou, Bernardino Ghetti, Pierluigi Gambetti, Byron Caughey

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Prions propagate as multiple strains in a wide variety of mammalian species. The detection of all such strains by a single ultrasensitive assay such as Real Time Quaking-induced Conversion (RT-QuIC) would facilitate prion disease diagnosis, surveillance and research. Previous studies have shown that bank voles, and transgenic mice expressing bank vole prion protein, are susceptible to most, if not all, types of prions. Here we show that bacterially expressed recombinant bank vole prion protein (residues 23-230) is an effective substrate for the sensitive RT-QuIC detection of all of the different prion types that we have tested so far – a total of 28 from humans, cattle, sheep, cervids and rodents, including several that have previously been undetectable by RT-QuIC or Protein Misfolding Cyclic Amplification. Furthermore, comparison of the relative abilities of different prions to seed positive RT-QuIC reactions with bank vole and not other recombinant prion proteins allowed discrimination of prion strains such as classical and atypical L-type bovine spongiform encephalopathy, classical and atypical Nor98 scrapie in sheep, and sporadic and variant Creutzfeldt-Jakob disease in humans. Comparison of protease-resistant RT-QuIC conversion products also aided strain discrimination and suggested the existence of several distinct classes of prion templates among the many strains tested.

Original languageEnglish
Article numbere1004983
JournalPLoS Pathogens
Volume11
Issue number6
DOIs
StatePublished - Jun 1 2015

Fingerprint

Arvicolinae
Prions
Sheep
Conversion Disorder
Bovine Spongiform Encephalopathy
Scrapie
Creutzfeldt-Jakob Syndrome
Prion Diseases
Aptitude
Recombinant Proteins
Transgenic Mice
Prion Proteins
Rodentia
Seeds
Peptide Hydrolases
Research
Proteins

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Orrú, C. D., Groveman, B. R., Raymond, L. D., Hughson, A. G., Nonno, R., Zou, W., ... Caughey, B. (2015). Bank Vole Prion Protein As an Apparently Universal Substrate for RT-QuIC-Based Detection and Discrimination of Prion Strains. PLoS Pathogens, 11(6), [e1004983]. https://doi.org/10.1371/journal.ppat.1004983

Bank Vole Prion Protein As an Apparently Universal Substrate for RT-QuIC-Based Detection and Discrimination of Prion Strains. / Orrú, Christina D.; Groveman, Bradley R.; Raymond, Lynne D.; Hughson, Andrew G.; Nonno, Romolo; Zou, Wenquan; Ghetti, Bernardino; Gambetti, Pierluigi; Caughey, Byron.

In: PLoS Pathogens, Vol. 11, No. 6, e1004983, 01.06.2015.

Research output: Contribution to journalArticle

Orrú, CD, Groveman, BR, Raymond, LD, Hughson, AG, Nonno, R, Zou, W, Ghetti, B, Gambetti, P & Caughey, B 2015, 'Bank Vole Prion Protein As an Apparently Universal Substrate for RT-QuIC-Based Detection and Discrimination of Prion Strains', PLoS Pathogens, vol. 11, no. 6, e1004983. https://doi.org/10.1371/journal.ppat.1004983
Orrú, Christina D. ; Groveman, Bradley R. ; Raymond, Lynne D. ; Hughson, Andrew G. ; Nonno, Romolo ; Zou, Wenquan ; Ghetti, Bernardino ; Gambetti, Pierluigi ; Caughey, Byron. / Bank Vole Prion Protein As an Apparently Universal Substrate for RT-QuIC-Based Detection and Discrimination of Prion Strains. In: PLoS Pathogens. 2015 ; Vol. 11, No. 6.
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