title: In vitro replication highlights the mutability of prions.
abstract: Prions exist as strains, which are thought to reflect PrP(Sc) conformational variants. Prion strains can mutate and it has been proposed that prion mutability depends on an intrinsic heterogeneity of prion populations that would behave as quasispecies. We investigated in vitro prion mutability of 2 strains, by following PrP(Sc) variations of populations serially propagated in PMCA under constant environmental pressure. Each strain was propagated either at low dilution of the seed, i.e., by large population passages, or at limiting dilution, mimicking bottleneck events. In both strains, PrP(Sc) conformational variants were identified only after large population passages, while repeated bottleneck events caused a rapid decline in amplification rates. These findings support the view that mutability is an intrinsic property of prions.
authors.affiliation: Department of Veterinary Public Health and Food Safety; Istituto Superiore di Sanità; Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Vanni
authors.affiliation: Department of Veterinary Public Health and Food Safety; Istituto Superiore di Sanità; Rome, Italy.
authors.forename: Michele Angelo
authors.initials: MA
authors.lastname: Di Bari
authors.affiliation: Department of Veterinary Public Health and Food Safety; Istituto Superiore di Sanità; Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pirisinu
authors.affiliation: Department of Veterinary Public Health and Food Safety; Istituto Superiore di Sanità; Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: D'Agostino
authors.affiliation: Department of Veterinary Public Health and Food Safety; Istituto Superiore di Sanità; Rome, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Agrimi
authors.affiliation: Department of Veterinary Public Health and Food Safety; Istituto Superiore di Sanità; Rome, Italy.
authors.forename: Romolo
authors.initials: R
authors.lastname: Nonno
mesh_terms: D000818:Animals; D003411:Arvicolinae; D015153:Blotting, Western; D066298:In Vitro Techniques; D009154:Mutation; D011328:Prions / Q000235:genetics / Q000502:physiology*
chemical_list: D011328:Prions
keywords: PMCA; PrPSc; Western blotting; prion; prion mutation; quasispecies