title: Synthetic prions with novel strain-specified properties.
abstract: Prions are infectious proteins that possess multiple self-propagating structures. The information for strains and structural specific barriers appears to be contained exclusively in the folding of the pathological isoform, PrP(Sc). Many recent studies determined that de novo prion strains could be generated in vitro from the structural conversion of recombinant (rec) prion protein (PrP) into amyloidal structures. Our aim was to elucidate the conformational diversity of pathological recPrP amyloids and their biological activities, as well as to gain novel insights in characterizing molecular events involved in mammalian prion conversion and propagation. To this end we generated infectious materials that possess different conformational structures. Our methodology for the prion conversion of recPrP required only purified rec full-length mouse (Mo) PrP and common chemicals. Neither infected brain extracts nor amplified PrP(Sc) were used. Following two different in vitro protocols recMoPrP converted to amyloid fibrils without any seeding factor. Mouse hypothalamic GT1 and neuroblastoma N2a cell lines were infected with these amyloid preparations as fast screening methodology to characterize the infectious materials. Remarkably, a large number of amyloid preparations were able to induce the conformational change of endogenous PrPC to harbor several distinctive proteinase-resistant PrP forms. One such preparation was characterized in vivo habouring a synthetic prion with novel strain specified neuropathological and biochemical properties.
authors.affiliation: Unit of Neuropathology and Neurology 5, IRCCS Foundation Carlo Besta Neurological Institute, Milano, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Moda
authors.affiliation: Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Ital,y.
authors.forename: Thanh-Nhat T
authors.initials: TN
authors.lastname: Le
authors.affiliation: Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Ital,y.
authors.forename: Suzana
authors.initials: S
authors.lastname: Aulić
authors.affiliation: Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Ital,y.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Bistaffa
authors.affiliation: Unit of Neuropathology and Neurology 5, IRCCS Foundation Carlo Besta Neurological Institute, Milano, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Campagnani
authors.affiliation: Unit of Neuropathology and Neurology 5, IRCCS Foundation Carlo Besta Neurological Institute, Milano, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Virgilio
authors.affiliation: Unit of Neuropathology and Neurology 5, IRCCS Foundation Carlo Besta Neurological Institute, Milano, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Indaco
authors.affiliation: Unit of Neuropathology and Neurology 5, IRCCS Foundation Carlo Besta Neurological Institute, Milano, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Palamara
authors.affiliation: UMR INRA-ENVT, Physiopathologie Infectieuse et Parasitaire des Ruminants, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Andréoletti
authors.affiliation: Unit of Neuropathology and Neurology 5, IRCCS Foundation Carlo Besta Neurological Institute, Milano, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tagliavini
authors.affiliation: Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Ital,y.|ELETTRA Laboratory, Sincrotrone Trieste S.C.p.A, Basovizza, Trieste, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Legname
mesh_terms: D000595:Amino Acid Sequence; D058227:Amyloidogenic Proteins / Q000737:chemistry; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004195:Disease Models, Animal; D051379:Mice; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D017096:Prion Diseases / Q000473:pathology*; D000072002:Prion Proteins; D011328:Prions / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D011994:Recombinant Proteins / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D058227:Amyloidogenic Proteins; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D011994:Recombinant Proteins