Sensitive protein misfolding cyclic amplification of sporadic Creutzfeldt-Jakob disease prions is strongly seed and substrate dependent.

ABSTRACT: Unlike variant Creutzfeldt-Jakob disease prions, sporadic Creutzfeldt-Jakob disease prions have been shown to be difficult to amplify in vitro by protein misfolding cyclic amplification (PMCA). We assessed PMCA of pathological prion protein (PrP^TSE) from 14 human sCJD brain samples in 3 substrates: 2 from transgenic mice expressing human prion protein (PrP) with either methionine (M) or valine (V) at position 129, and 1 from bank voles. Brain extracts representing the 5 major clinicopathological sCJD subtypes (MM1/MV1, MM2, MV2, VV1, and VV2) all triggered seeded PrP^TSE amplification during serial PMCA with strong seed- and substrate-dependence. Remarkably, bank vole PrP substrate allowed the propagation of all sCJD subtypes with preservation of the initial molecular

SUBMITTER: Belondrade M 

PROVIDER: S-EPMC7893054 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature