Trasmissione intraspecie di encefalopatia spongiforme bovina e di encefalopatia spongiforme amiloidotica bovina. Caratterizzazione molecolare e ultrastrutturale di un nuovo ceppo di prione nel bovino

Transmissible Spongiform Encephalopathies (TSE) or Prion diseases are a group of rare, fatal and transmissible neurodegenerative disorders that affect both humans and animals. Clinically these diseases exist in sporadic, genetic and acquired forms, and present with a variety of neurological signs. TSE diseases are characterized by accumulation, primarily in the brain, of an abnormal isoform of the normal host-encoded prion protein (PrPC), named PrPSc that is considered the disease-associated agent. The central event of the TSE is a post-translational conformational change of the PrPC, a plasma membrane glycoprotein, rich in α-helix, into the PrPSc that has a higher β-sheet content. In bovine there are two forms of TSE: Bovine Spongiform Encephalopathy (BSE) and Bovine Amyloidotic Spongiform Encephalopathy (BASE). After the epidemy in cattle in UK in 1985, many researches characterized the phenotype and the biochemistry of PrPSc in BSE. Recently new atypical forms of BSE are discovered and called BSE-H (higher) and BSE-L (lower) for the different molecular mass of unglycosilated isoform of PrPSc. Also BASE is classified as atypical BSE with a prion protein similar to BSE-L and it is distinguishable from BSE for differences in pattern of deposition, consistent in the presence of amyloid plaques, in distinct molecular masses and in glycosilation profile of prion isoforms. These observations suggest that cattle may have two distinct prion strains, refered to two forms of TSE and that prion protein of BASE could be the same of BSE-L. Also recent studies on PrP-bovinized transgenic mice have showed that BASE is a more aggressive disease than BSE, characterized by shorter period of incubation. To investigate the characteristics of prion strains responsible of BSE and BASE, we carried out transmission by inoculation of BSE and BASE isolates in Fresian and Alpine brown cattle. Intraspecies transmission permitted firstly to reduce the period of incubation, overcoming the species barrier, and secondly to identify the phenotype of BASE. BASE inoculated cattle showed a progressive muscle atrophy and a dull behaviour, in contrast with aggressiveness and hypersensitivity of BSE-infected animals. The prion strains of inoculi preserved their different biochemical and neuropathological properties also after transmission. Finally, a more detailed ultrastructural analysis confirmed the distinction in patterns of PrPSc deposition and it showed different subcellular localization of prion protein between BSE and BASE infected bovine. By evaluation of biochemical, immunoistochemical and ultrastructural results, our study gave an improvement in the characterization of BASE prion strain, describing the clinical phenotype.