Divergent prion strain evolution driven by PrPC expression level in transgenic mice

Annick Le Dur, Thanh Lan Laï, Marie-George Stinnakre, Aude Laisné, Nathalie Chenais, Sabine Rakotobe, Bruno Passet, Fabienne Reine, Solange Soulier, Laetitia Herzog, Gaëlle Tilly, Human Rézaei, Vincent Béringue, Jean-Luc Vilotte and Hubert Laude ()
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Annick Le Dur: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay
Thanh Lan Laï: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay
Marie-George Stinnakre: Génétique Animale et Biologie Intégrative (GABI), INRA, AgroParisTech, Université Paris-Saclay
Aude Laisné: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay
Nathalie Chenais: Génétique Animale et Biologie Intégrative (GABI), INRA, AgroParisTech, Université Paris-Saclay
Sabine Rakotobe: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay
Bruno Passet: Génétique Animale et Biologie Intégrative (GABI), INRA, AgroParisTech, Université Paris-Saclay
Fabienne Reine: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay
Solange Soulier: Génétique Animale et Biologie Intégrative (GABI), INRA, AgroParisTech, Université Paris-Saclay
Laetitia Herzog: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay
Gaëlle Tilly: Génétique Animale et Biologie Intégrative (GABI), INRA, AgroParisTech, Université Paris-Saclay
Human Rézaei: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay
Vincent Béringue: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay
Jean-Luc Vilotte: Génétique Animale et Biologie Intégrative (GABI), INRA, AgroParisTech, Université Paris-Saclay
Hubert Laude: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract Prions induce a fatal neurodegenerative disease in infected host brain based on the refolding and aggregation of the host-encoded prion protein PrPC into PrPSc. Structurally distinct PrPSc conformers can give rise to multiple prion strains. Constrained interactions between PrPC and different PrPSc strains can in turn lead to certain PrPSc (sub)populations being selected for cross-species transmission, or even produce mutation-like events. By contrast, prion strains are generally conserved when transmitted within the same species, or to transgenic mice expressing homologous PrPC. Here, we compare the strain properties of a representative sheep scrapie isolate transmitted to a panel of transgenic mouse lines expressing varying levels of homologous PrPC. While breeding true in mice expressing PrPC at near physiological levels, scrapie prions evolve consistently towards different strain components in mice beyond a certain threshold of PrPC overexpression. Our results support the view that PrPC gene dosage can influence prion evolution on homotypic transmission.

Date: 2017
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DOI: 10.1038/ncomms14170

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