Experimental Scrapie in Golden Syrian Hamsters: Temporal Comparison of in Vitro Cell-fusing Activity with Brain Infectivity and Histopathological Changes

Golden Syrain hamsters were inoculated intracerebrally with the hamster-adapted 263K strain of scrapie virus, and the evolution of in vitro cell fusing activity induced by brain suspensions was compared with brain infectivity titers and histological changes. Cell-fusing activity abruptly appeared 4 weeks after inoculation, 1 week before the earliest detectable histopathological changes, at an infectivity level of 7.6 log 50% lethal doses per g of brain. Cell-fusing activity was sustained throughout the remaining 4 weeks of the incubation period and the subsequent 1- to 3-week stage of clinical illness but did not increase with the logarithmic progression of infectivity, which reached a level of 11 log 50% lethal doses per g in the agonal stage of disease. Gliosis was most sensitively detected by a monoclonal antibody reacting with astrocyte intermediate filaments in an indirect immunofluorescence test, anticipating histological recognition of gliosis and spongiform change by 1 to 2 weeks. In vitro cell-fusing activity is thus one of the earliest known biological markers (apart from infectivity itself) of experimental scrapie infection.