Prion strains in mammals: Different conformations leading to disease

Prion diseases are neurodegenerative disorders affecting mammals with a diverse etiology. Although rare, most of the cases occur spontaneously in humans, with a minority being inherited or acquired by infection. Prion disease in ruminants such as sheep, goat, and deer are relatively frequent and likely feed borne [1] or environmentally transmitted [2]. The confirmed zoonotic potential of bovine spongiform encephalopathy (BSE) and the still unknown consequences of other animal prionopathies to humans have placed these diseases in the spotlight. “Prions” refers to proteinaceous infectious particles. This concept was originally defined after the pathological properties of the disease-associated prion protein (also termed PrP). These unique infectious agents exist in a wide variety of “strains.” Prion strain variation was first suggested in 1961 by Pattison and Millson, who identified different phenotypes in experimentally infected goats [3]. This concept was later proven in inbred laboratory rodents, which also showed prion disease-specific phenotypes, brain-lesion profiles, and incubation periods [4]. The existence of prion strains was originally difficult to rationalize with the idea that the causative agent in these diseases was composed only by misfolded proteins, particularly considering that, in most cases, strain variation was documented within the same animal species (expressing a single cellular prion protein [PrP] sequence). Current evidence suggests that the main difference between prion strains lies in the different conformational arrangements that PrP acquires [5]. These infectious particles “transmit” their particular conformational motifs to the normally folded proteins expressed in the host, leading to specific disease features.