P.K. Nandi ^{a, @},  and J.-C. Nicole ^b

^a Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France
^b Physiologie de la Reproduction des Mammifères Domestiques, Institut National de la Recherche Agronomique, 37380 Nouzilly, France

^@ E-mail:  nandi@tours.inra.fr

The infectious agent of transmissible spongiform encephalopathies (TSE) has been considered to be
PrP^SC, a structural isoform of cellular prion protein PrP^C. PrP^SC can exist as oligomers and/or as
amyloid polymers. Nucleic acids induce structural conversion of recombinant prion protein PrP and
PrP^C to PrP^SC form in solution and in vitro. Here, we report that nucleic acids, by interacting with
PrP in solution, produce amyloid fibril and fibres of different morphologies, similar to those identified
in the diseased brains. In addition, the same interaction produces polymer lattices and spherical
amyloids of different dimensions (15–150 nm in diameters). The polymer lattices show apparent
morphological similarity to the two-dimensional amyloid crystals obtained from linear amyloids
isolated in vivo. The spherical amyloids structurally resemble “spherical particles” observed in
natural spongiform encephalopathy (SE) and in scrapie-infected brains (TSE). We suggest that
spherical amyloids, PrP^SC-amylospheroids, are probable constituents of the coat of the spherical
particles found in vivo and the latter can act as protective coats of the SE and TSE agents in vivo.

Keywords: prion protein; prion protein–nucleic acid interaction; prion protein oligomers; amyloid fibres; spherical amyloids

Abbreviations used: PrP^C, cellular prion protein; PrP^SC, infectious or scrapie isoform of PrP^C;
    PrP, mouse recombinant prion protein; SE, natural spongiform encephalopathy; TSE, transmissible
    spongiform encephalopathy; CJD, Creutzfeldt-Jakob disease; gcDNA, synthetic double-stranded
    nucleic acids consisting of guanine and cytosine bases; PolyA, synthetic polymer of adenosine
    phosphate, used as a model for single-stranded nucleic acids; PK, proteinase K 

a. Adler V, Zeiler B, Kryukov V, Kascsak R, Rubenstein R, and Grossman A, "Small, Highly Structured RNAs Participate in the Conversion of Human Recombinant PrP^Sen to PrP^Resin vitro".

b. Deleault NR, Lucassen RW, and Supattapone S, "RNA Molecules Stimulate Prion Protein Conversion".

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