title: Divergent prion strain evolution driven by PrPCexpression level in transgenic mice.
abstract: Prions induce a fatal neurodegenerative disease in infected host brain based on the refolding and aggregation of the host-encoded prion protein PrPCinto PrPSc. Structurally distinct PrPScconformers can give rise to multiple prion strains. Constrained interactions between PrPCand different PrPScstrains 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 PrPCat near physiological levels, scrapie prions evolve consistently towards different strain components in mice beyond a certain threshold of PrPCoverexpression. Our results support the view that PrPCgene dosage can influence prion evolution on homotypic transmission.
authors.affiliation: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Le Dur
authors.affiliation: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Thanh Lan
authors.initials: TL
authors.lastname: Laï
authors.affiliation: Génétique Animale et Biologie Intégrative (GABI), INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Marie-George
authors.initials: MG
authors.lastname: Stinnakre
authors.affiliation: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Laisné
authors.affiliation: Génétique Animale et Biologie Intégrative (GABI), INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chenais
authors.affiliation: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Rakotobe
authors.affiliation: Génétique Animale et Biologie Intégrative (GABI), INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Passet
authors.affiliation: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Reine
authors.affiliation: Génétique Animale et Biologie Intégrative (GABI), INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Solange
authors.initials: S
authors.lastname: Soulier
authors.affiliation: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Herzog
authors.affiliation: Génétique Animale et Biologie Intégrative (GABI), INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Tilly
authors.affiliation: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Human
authors.initials: H
authors.lastname: Rézaei
authors.affiliation: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Béringue
authors.affiliation: Génétique Animale et Biologie Intégrative (GABI), INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Vilotte
authors.affiliation: Virologie Immunologie Moléculaires (VIM), INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Laude
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D005786:Gene Expression Regulation / Q000502:physiology*; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D012756:Sheep
chemical_list: D018621:PrPC Proteins