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Prions are unconventional transmissible agents causing fatal neurodegenerative diseases in mammals, known as transmissible spongiform encephalopathies (or TSE). TSEs, also called prion diseases, include Creutzfeldt-Jakob disease in humans, scrapie in sheep and goats, and bovine spongiform encephalopathy (BSE) in cattle. Prion diseases are characterized by the degeneration of the central nervous system (CNS), targeting both the brain and spinal cord, following prion replication in the infected host. Anatomically, the main hallmarks of these diseases are brain vacuolation - giving a spongious aspect-, neuronal death and the accumulation of particles made of abnormally folded prion proteins.

Abnormal prion protein distribution in brain slices following infection by 2 different strains.

Prions are thought to be formed from polymers of abnormal conformations of the host-encoded prion protein (PrP), but little is known about the physical organization of the infectious particles and any relationship between packing order and infectivity. As an additional layer of complexity, different PrP conformational variants associated with distinct biological phenotypes, or ‘strains’, can propagate in the same host.

Scientists from INRA Jouy-en-Josas subjected PrP polymers from 8 different ovine and hamster prion strains to sedimentation velocity centrifugation, which allows separation of macromolecular complexes according to their size, density or shape. They showed that, whereas the PrP sedimentation profiles share common features, the infectivity profiles exhibit striking differences amongst the strains. For 4 of them, the infectious component was predominantly associated with slowly sedimenting particles, suggestive of small size oligomers and/or low density PrP aggregates. Such particles appeared to be a feature of strains able to induce a rapidly lethal disease in the recipient host.

These findings suggest that prion infectious particles are subjected to marked strain-dependent variations, which in turn could influence the strain biological phenotype, in particular the replication dynamics.

Reference :

The physical relationship between infectivity and prion protein aggregates is strain dependent. PLoS Pathogens, 15 April 2010.

Philippe Tixador, Laëtitia Herzog, Fabienne Reine, Emilie Jaumain, Jérôme Chapuis, Annick Le Dur, Hubert Laude and Vincent Béringue

INRA (Institut National de la Recherche Agronomique)
 UR892, Virologie Immunologie Moléculaires
 F-78350 Jouy-en-Josas, France