Scrapie pathogenesis.

There is no specific marker for scrapie infectivity, and therefore no means other than prolonged bioassay for estimating levels of infection in tissues. Our knowledge of replication dynamics depends on precise rodent models which have enabled us to determine how the disease spreads and in which cells it replicates. We know, firstly, that infection replicates in the lymphoreticular system, and can identify a candidate cell; secondly, the factors which control the length of the disease process, and how difficult it is to influence this; thirdly, that clinical disease depends on access to the nervous system, and that once neuroinvasion has occurred, the spread of infectivity in both PNS and CNS is along neuroanatomical pathways at a similar rate to slow axonal transport in uninfected mice. Infecting the visual pathways of the CNS through the retina has shown that spongiform pathology occurs as a consequence of replication, and that the Sinc gene, which has a major effect on incubation period length in mice, acts by controlling the initiation, but not the rate, of replication. The localisation of PrP, a host protein of unknown function which accumulates in an abnormal form in diseased animals provides an important pointer to pathogenetic mechanisms.