A comparison of some biological characteristics of the mouse-passaged scrapie agents, 22A and ME7

Abstract

Two mouse-adapted scrapie agents of different sheep origin were compared. The titre, reached in the brains of mice in the terminal stage of scrapie, is of the same order for both agents. There is a threefold difference between the incubation periods of the two agents in some mouse strains, of which C57 is one, and in this strain incubation of the 22A agent, given as a large dose by a peripheral route, occupies almost the whole life-span.The most fundamental difference between the agents concerns the reversal of the ranking of incubation periods, typically in the VM and C57 mouse strams: incubation of ME7 in VM takes almost twice as long as in C57, whereas most sub-lines of 22A take half as long in VM as in C57. The implications of this type of host-genotype, agent-strain interaction are discussed in terms of the possible nature of agent differences, the possibility of latent infection and the consequences for scrapie eradication programmes.

Genetic Control of Scrapie: Incubation Period and Plaque Formation in I Mice

“…The specificity of Sinc for different scrapie strains could relate to specific interactions with sequences of the agent genome. One possibility, though not particulary likely, is that agent replication is at the level of the host chromosome (Dickinson & Meikle, 1969). If this were so, the possibility has had to be entertained that a mutation from s7 to p7 in Edinburgh might have been induced directly by scrapie agent.…”

“…Many scrapie strains have a similar pattern in terms of these two alleles, but other strains (e.g. 22A and 87V) have an opposite pattern with a longer incubation period in s7 than in p7 inbred mouse strains (Dickinson & Meikle, 1969, 1971Dickinson & Fraser, 1977;Dickinson et al, 1984). Other genes are known to influence incubation period, but their effects are trivial compared to Sinc; also they have never been found to alter the ranking of incubation periods in different Sine genotypes (Outram, 1976;Kingsbury et al, 1983;Bruce & Dickinson, 1985).…”

Prions

“…Naturally occurring prion strains have been isolated, each with a distinct incubation period and characteristic pathology; these traits are often conserved on serial transmission (Dickinson and Meikle 1969;Fraser and Dickinson 1973). Because prions are composed only of protein and replicate using the PrP substrate present in the host, differences in prion strains cannot be attributed to genetic variability, which accounts for the existence of viral strains.…”

Abbreviated incubation times for human prions in mice expressing a chimeric mouse–human prion protein transgene

“…However, additional studies are required to test this conjecture, including end-point titrations, which yield dose-response curves. The slopes of these curves have been used to distinguish different prion strains (32).…”