Classical sheep transmissible spongiform encephalopathies: pathogenesis, pathological phenotypes and clinical disease

M. Jeffrey and L. González (2007) Neuropathology and Applied Neurobiology33, 373–394
Classical sheep transmissible spongiform encephalopathies: pathogenesis, pathological phenotypes and clinical disease

ABSTRACT

Scrapie is a prion disease or transmissible spongiform encephalopathy (TSE) of sheep, goats and moufflon. As with its human counterparts, pathology consists of vacuolation, gliosis and accumulations of abnormal forms of a host prion protein (PrP^d) in the brain of affected individuals. Immunohistochemical methods can be used to identify both the intracellular truncation sites of PrP^d in different cell types (PrP^d epitope mapping) and the different morphological patterns of accumulation (PrP^d profiling). Differences in the inferred truncation sites of PrP^d are found for different strains of sheep TSEs and for different infected cell types within individual strains. Immunochemical methods of characterizing strains broadly correspond to PrP^d mapping discriminatory results, but distinct PrP^d profiles, which provide strain- and source-specific information on both the cell types which sustain infection (cellular tropisms) and the cellular processing of PrP^d, have no immunoblotting counterparts. The cause of neurological dysfunction in human is commonly considered to be neuronal loss secondary to a direct or indirect effect of the accumulation of PrP^d. However, in sheep scrapie there is no significant neuronal loss, and relationships between different magnitudes, topographical and cytological forms of PrP^d accumulation and clinical signs are not evident. PrP^d accumulation also occurs in lymphoid tissues, for which there is indirect evidence of a pathological effect, in the peripheral nervous system and in other tissues. It is generally assumed that neuroinvasion results from infection of the enteric nervous system neurones subsequent to amplification of infectivity in lymphoid tissues and later spread via sympathetic and parasympathetic pathways. The evidence for this is, however, circumstantial. Accumulation of PrP^d and presence of infectivity in tissues other than the nervous and lymphoreticular systems gives insights on the ways of transmission of infection and on food safety.