Scrapie: How Much Do We Really Understand?

Abstract

Biological studies have produced convincing evidence for different scrapie strains, some of which undergo mutation. This argues strongly in favour of the infectious scrapie agent having a genome. The length of incubation period is influenced by the strain of agent but is also under strict host control. In mice, this control is exerted by a gene called Sinc which affects the overall rate of agent replication in the CNS. After peripheral infection, invasion of the CNS from lymphoreticular sites of agent replication is a key step in pathogenesis. Evidence from one scrapie model indicates spread of infection along autonomic nerves to the thoracic spinal cord and then to other parts of the CNS. Other studies have shown that infection can spread in neurons. There are close relationships between the presence of replicating agent and the development of vacuolation, and also of cerebral amyloid when it occurs. We can, therefore, begin to understand the patterns of lesion development in the brain in terms of the targeting of infection and its replication at certain sites. Structures known as SAF (Scrapie Associated Fibrils) have been discovered in extracts of scrapie brain (but not uninfected brain) and a glycoprotein (PrP 27-30: SAF protein) is a major constituent of purified SAF. The glycoprotein is coded by a single gene which is present in several species and expressed in uninfected brain. The normal protein seems to be modified in scrapie infected brain so that it accumulates as SAF. The modified protein may also be deposited as extracellular amyloid because there appear to be common epitopes between SAF and scrapie amyloid. The biochemical nature of the scrapie agent remains in doubt and the association between infectivity and purified SAF may arise fortuitously from the fact that scrapie agent is 'sticky'.

Indeterminacy in‐decisions – science, policy and politics in the BSE (Bovine Spongiform Encephalopathy) crisis

“…Indeed, the prion hypothesis seemed to open up rather than close down scientific conflict. One of the key opponents to the prion hypothesis was Richard Kimberlin (see for example, Kimberlin 1982Kimberlin , 1986) -who, despite the official decision to exclude scientists involved in controversies over TSE, was to become one of the main scientific advisers and risk analysts in the BSE debacle. Kimberlin was wary of abandoning conventional thinking on disease and replication, and noted that the existence of transmissible strains of the disease suggested that nucleic acid needed to be present in the agent in order to convey this strain specific information.…”

Iatrogenic transmission of Creutzfeldt-Jakob disease

“…Intramuscular injection of the scrapie agent is followed by invasion of the central nervous system from lymphoreticular sites of agent replication. In one scrapie model, spread of the agent occurs along autonomic nerves to the thoracic spinal cord and thence to other parts of the central nervous system (Kimberlin, 1986). Other studies suggest that the scrapie agent spreads in neurons.…”

“…Other studies suggest that the scrapie agent spreads in neurons. There is a close relationship between the presence of replicating scrapie agent and the vacuolated spongiform change in the cerebral cortex (Kimberlin, 1986).…”

“…In addition to intracerebral injection, both scrapie and Creutzfeldt-Jakob disease can be transmitted by oral routes and by peripheral injections (Kimberlin, 1986). Intramuscular injection of the scrapie agent is followed by invasion of the central nervous system from lymphoreticular sites of agent replication.…”

“…acid associated with scrapie and possibly the Creutzfeldt-Jakob infectious agents (Kimberlin, 1986).…”