Molecular Barriers to Zoonotic Transmission of Prions

Abstract

Chronic wasting disease in elk might be a threat to human health.

Genotype-dependent Molecular Evolution of Sheep Bovine Spongiform Encephalopathy (BSE) Prions in Vitro Affects Their Zoonotic Potential

“…This suggests that the known zoonotic potential of the BSE agent is recapitulated in this cell-free prion protein conversion assay irrespective of the host species (cow, sheep, or human). We have also shown that classical BSE cattle brain homogenates have a greater potential to convert human PrP C in PMCA than any other tested animal prion disease (39). Here we show that samples of experimental sheep BSE isolates of the VRQ/ VRQ, ARQ/ARQ, and ARR/ARR genotypes are all able to convert human PrP C during a single round of PMCA and that the preference is for the PRNP codon 129 M over the V allele (Table 1).…”

“…The sCJD sample was from a patient with a diagnosis of sporadic CJD (VV2 subtype). The non-CJD human brain specimens used for PMCA substrate preparation were from frontal cortex from patients with Guillain-Barré syndrome (PRNP codon 129 MM) and dementia with Lewy bodies (PRNP codon 129 VV), and their use as PMCA substrates has been described previously (39).…”

Human prion protein sequence elements impede cross-species chronic wasting disease transmission

“…Human prion proteinexpressing (PrP-expressing) transgenic mice resist CWD infection, suggesting a strong barrier for CWD transmission to humans (9)(10)(11)(12); however, certain non-human primates are CWD susceptible (13)(14)(15)(16). Similarly conflicting results from studies performed in vitro showed that CWD prions either efficiently or poorly convert human PrP to a pathogenic isoform (14,(17)(18)(19). Thus, no consensus has emerged on the susceptibility of humans to CWD prions, and the transmission of CWD to humans remains a major public health concern.…”

Variant CJD

“…An alternative to modeling the species barrier is the cell-free conversion assay which points to CWD as the animal prion disease with the greatest zoonotic potential, after (and very much less than) BSE. 116 …”