Pathogenesis of Scrapie: Study of the Temporal Development of Clinical Symptoms, of Infectivity Titres and Scrapie-associated Fibrils in Brains of

After an intraperitoneal infection of hamsters with scrapie agent, early low and constant titres of about 100 LD50/brain between days 10 to 50 were followed by a dramatic increase to maximum levels of 3 x 109 LDs0/brain within about 15 days. The plateau of maximum infectivity remained unchanged from day 70 to the time of the first and final signs of disease at 95 and 123 days post-infection, respectively. Scrapie-associated fibrils (SAF) as measured by immunoblotting of SAF protein could not be detected before 79 days post-infection even when a total brain was used for analysis. Subsequently, the concentration f SAF increased gradually by about 10000-fold until the time of clinical disease. The kinetics suggest a virus-induced amyloidosis of the brain as the cause of disease. Unconventional slow viruses cause slow, progressive, degenerative diseases of the central nervous system (for review, see Gajdusek, 1985). Kinetic studies of the appearance and distribution of infectivity in mice after a peripheral (subcutaneous) infection with the scrapie agent revealed (i) that infectivity spreads rapidly to various organs in the periphery, reaching the earliest and highest titres in spleen and lymph nodes without histopathology and (ii) that measurable titres in the target organ, the brain, appear late after infection, reaching higher titres than in any other organ prior to the onset of clinical symptoms (Eklund et al., 1967). Here we report data on virus replication and the production of disease-specific s rapie