Nucleic acid and prion protein interaction produces spherical amyloids which can function in vivo as coats of spongiform encephalopathy agent

The infectious agent of transmissible spongiform encephalopathies (TSE) has been considered to be PrPSC, a structural isoform of cellular prion protein PrPC. PrPSC can exist as oligomers and/or as amyloid polymers. Nucleic acids induce structural conversion of recombinant prion protein PrP and PrPC to PrPSC 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, PrPSC-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. (C) 2004 Elsevier Ltd. All rights reserved.