Synthetic prions with novel strain-specified properties

PLoS Pathog. 2015 Dec 31;11(12):e1005354. doi: 10.1371/journal.ppat.1005354. eCollection 2015 Dec.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloidogenic Proteins / chemistry
  • Animals
  • Blotting, Western
  • Cell Line
  • Disease Models, Animal
  • Mice
  • Microscopy, Atomic Force
  • Molecular Sequence Data
  • Prion Diseases / pathology*
  • Prion Proteins
  • Prions / chemical synthesis
  • Prions / chemistry*
  • Prions / metabolism*
  • Protein Conformation
  • Protein Folding
  • Recombinant Proteins / chemical synthesis
  • Recombinant Proteins / chemistry


  • Amyloidogenic Proteins
  • Prion Proteins
  • Prions
  • Prnp protein, mouse
  • Recombinant Proteins

Grant support

GL has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 222887 – the PRIORITY project – and from the Ministero dell'Istruzione, dell'Università e della Ricerca under the program PRIN 2008 “Meccanismi Neurodegenerativi nelle Malattie da Prioni: Studi Conformazionali, Fisiopatologia della Proteina Prionica e Possibili Approcci Farmacologici”. The work was partially supported by the Italian Ministry of Health to FT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.