Competition between Different Scrapie Agents in Mice

Abstract

STRAINS of scrapie agent differ in a number of their biological properties, one of which is average incubation period^1,2. Incubation period is inversely proportional to dose for all known strains of scrapie and some differ so markedly that there is no overlap in their dose-incubation period curves. A large dose of one agent takes longer to produce the disease than the LD₅₀ dose of another agent³. Two such scrapie agents are 22A and 22C when compared by intracerebral injection of VM mice. Agent 22A has a much shorter incubation period than 22C in VM mice because they carry the p7 allele of the sine gene that controls scrapie incubation. It should therefore be possible to produce mixed infections in VM mice, but to ensure that the clinical disease is produced by the 22A agent. It can be checked that 22A causes the disease, rather than 22C, by examining the distribution of brain lesions². Interaction during pathogenesis between the two agents—competition or synergism—would be seen as a difference in the incubation period of 22A. We achieved mixed infection by injecting 22C first and 22A on a later occasion.