Abstract
The key event in prion pathogenesis is the structural conversion of the normal cellular protein, PrPC, into an aberrant and partially proteinase K resistant isoform, PrPSc. Since the minimum requirement for a prion disease phenotype is the expression of endogenous PrP in the host, species carrying orthologue prion genes, such as fish, could in theory support prion pathogenesis. Our previous work has demonstrated the development of abnormal protein deposition in sea bream brain, following oral challenge of the fish with natural prion infectious material. In this study, we used a prion-infected mouse neuroblastoma cell line for the expression of three different mature fish PrP proteins and the evaluation of the resistance of the exogenously expressed proteins to proteinase K treatment (PK), as an indicator of a possible prion conversion. No evidence of resistance to PK was detected for any of the studied recombinant proteins. Although not indicative of an absolute inability of the fish PrPs to structurally convert to pathogenic isoforms, the absence of PK-resistance may be due to supramolecular and conformational differences between the mammalian and piscine PrPs.
Highlights
Transmissible Spongiform Encephalopathies (TSEs), commonly known as prion diseases, are fatal neurodegenerative diseases affecting a wide range of species, varying from humans to rodents
The coding sequences corresponding to the mature protein fragments of ZebPrP-1, ZebPrP-2 and SaurPrP-1 were introduced into pcDNA3.1 constructs flanked by the sequences coding for the murine PrP N- and C-terminal signal peptides (SP) (Figure 2)
Our findings suggest that the fish prion proteins very likely underwent a mammalian-like biosynthetic process in the 22L-ScN2a cells, which resulted in their immunodetection both at the plasma membrane and intracellularly, where they might have been exposed to the endogenous PrPSc
Summary
Transmissible Spongiform Encephalopathies (TSEs), commonly known as prion diseases, are fatal neurodegenerative diseases affecting a wide range of species, varying from humans to rodents. Inter-species transmission of TSEs is limited by the so called “species barrier”. The magnitude of such a barrier reflects the ease by which prions can be transmitted from one species to another, the number of the affected animals, the duration of the incubation period, and the clinical and histopathological manifestations of the disease in the new host [3]. The structural homology, in addition to the amino acid sequence identity, between the donor and host PrP molecules, has been considered as one of the critical parameters affecting the existence and characteristics of a transmission barrier between two species [4,5,6]
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