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A New Cell Model for Investigating Prion Strain Selection and Adaptation

Philiastides, A; Ribes, JM; Yip, DC-M; Schmidt, C; Benilova, I; Klöhn, P-C; (2019) A New Cell Model for Investigating Prion Strain Selection and Adaptation. Viruses , 11 (10) , Article 888. 10.3390/v11100888. Green open access

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Abstract

Prion diseases are fatal neurodegenerative diseases that affect humans and animals. Prion strains, conformational variants of misfolded prion proteins, are associated with distinct clinical and pathological phenotypes. Host-strain interactions result in the selective damage of distinct brain areas and they are responsible for strain selection and/or adaptation, but the underlying molecular mechanisms are unknown. Prion strains can be distinguished by their cell tropism in vivo and in vitro, which suggests that susceptibility to distinct prion strains is determined by cellular factors. The neuroblastoma cell line PK1 is refractory to the prion strain Me7, but highly susceptible to RML. We challenged a large number of clonal PK1 lines with Me7 and successfully selected highly Me7-susceptible subclones (PME) to investigate whether the prion strain repertoire of PK1 can be expanded. Notably, the Me7-infected PME clones were more protease-resistant when compared to RML-infected PME clones, which suggested that cell-adapted Me7 and RML are distinct prion strains. Strikingly, Me7-refractory cells, including PK1 and astrocytes in cortico-hippocampal cultures, are highly susceptible to prions, being derived from homogenates of Me7-infected PME cells, suggesting that the passage of Me7 in PME cells leads to an extended host range. Thus, PME clones represent a compelling cell model for strain selection and adaptation.

Type: Article
Title: A New Cell Model for Investigating Prion Strain Selection and Adaptation
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/v11100888
Publisher version: https://doi.org/10.3390/v11100888
Language: English
Additional information: This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Keywords: prions; prion strains; neurodegeneration; selective neuronal vulnerability; adaptation; prion propagation; astrocytes; neurons
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Institute of Prion Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Institute of Prion Diseases > MRC Prion Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10082209
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