In vitro Modeling of Prion Strain Tropism.

Etienne Levavasseur,Nicolas Privat,Stéphane Haïk

doi:10.3390/v11030236

Abstract

Prions are atypical infectious agents lacking genetic material. Yet, various strains have been isolated from animals and humans using experimental models. They are distinguished by the resulting pattern of disease, including the localization of PrPsc deposits and the spongiform changes they induce in the brain of affected individuals. In this paper, we discuss the emerging use of cellular and acellular models to decipher the mechanisms involved in the strain-specific targeting of distinct brain regions. Recent studies suggest that neuronal cultures, protein misfolding cyclic amplification, and combination of both approaches may be useful to explore this under-investigated but central domain of the prion field.

Highlights

Prion diseases are a group of rare progressive neurodegenerative disorders that affect both humans and animals
Recent evidence from experiments using models for these newly identified molecules will be helpful to validate their role in modulating the primary infected cultures supports that a strain-specific tropism for different types of neuronal prion-strain tropism
Region-specific protein mis-folding cyclic amplification (PMCA) suggests that such a neuronal tropism involves molecular factors in addition to the potential role of cell functions and cell-to-cell interactions that may differ between

Summary

Introduction

Prion diseases are a group of rare progressive neurodegenerative disorders that affect both humans and animals. By correlating codon 129 genotype and PrPres types with clinical and pathological features in sporadic CJD, various molecular combinations corresponding to the most common phenotypic variants of sCJD were identified [4,8] They contain no nucleic acids, different prion strains can be propagated in experimental models [9]. Transmission experiments demonstrated that the same prion strain is associated with the vCJD cases observed in different countries [18] Despite such evidence of a strain-specific tropism leading to preferential replication in given brain regions, the cellular mechanisms involved in this phenomenon have been marginally studied in the field. They provide the first evidence of a strain-specific neuronal tropism that may involve local molecular cofactors implicated in the PrP conversion process

Cellular Models of Prion Strain Tropism

Acellular Models of Prion Strain Tropism

Combining Cellular with Acellular Models