Organ-specific modification of the dose-response relationship of scrapie infectivity

Abstract

The dose-response relationships of scrapie strain 263K-infected hamster brain and spleen homogenates were compared to determine if intracerebral end-point titrations of infectivity in these homogenates were measures of the same pathogenic phenomenon. Analysis of the dose-response curves indicated that the average increase in incubation period per 10-fold dilution (i.e., the dilution kinetics) of brain infectivity was significantly different from that of spleen infectivity. This difference contradicted the assumption that the same pathogen or pathogenic mechanisms were responsible for producing disease in each titration. Therefore, the end-point titrations and infectivity titers of the brain and spleen homogenates were measures of two different phenomena. Subsequent passage of a scrapie-infected spleen homogenate demonstrated that the dose-response relationship of scrapie infectivity in this agent-host system was dependent on the organ titrated, not the tissue source or inoculation route of previous passage.