Synthetic prions with novel strain-specified properties

Fabio Moda, Thanh Nhat T. Le, Suzana Aulić, Edoardo Bistaffa, Ilaria Campagnani, Tommaso Virgilio, Antonio Indaco, Luisa Palamara, Olivier Andréoletti, Fabrizio Tagliavini, Giuseppe Legname

Research output: Contribution to journalArticle

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, PrPSc. 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 PrPSc 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.

Original languageEnglish
Article numbere1005354
JournalPLoS Pathogens
Volume11
Issue number12
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Fingerprint Dive into the research topics of 'Synthetic prions with novel strain-specified properties'. Together they form a unique fingerprint.

  • Cite this

    Moda, F., T. Le, T. N., Aulić, S., Bistaffa, E., Campagnani, I., Virgilio, T., Indaco, A., Palamara, L., Andréoletti, O., Tagliavini, F., & Legname, G. (2015). Synthetic prions with novel strain-specified properties. PLoS Pathogens, 11(12), [e1005354]. https://doi.org/10.1371/journal.ppat.1005354