Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and the species barrier

Abstract

Transmissions of bovine spongiform encephalopathy (BSE) from seven unrelated cattle sources have given remarkably uniform disease characteristics in mice, differing from over twenty previous and contemporary transmissions of sheep and goat scrapie. Transmissions to mice of spongiform encephalopathy from six species (including sheep and goats) which have been experimentally or naturally infected with BSE have given similar results to direct BSE transmissions from cattle. Therefore the BSE agent has retained its identity when passaged through a range of species and the 'donor' species has little specific influence on disease characteristics in mice, adding to evidence for an agent-specific informational molecule. On transmission of BSE or scrapie to mice the incubation periods are long compared with subsequent mouse-to-mouse passages (the 'species barrier'). Contributing factors include a low efficiency of infection on interspecies transmission, the apparent failure of intracerebrally injected 'foreign' inoculum to establish infection directly in mouse brain and the selection of variant strains of agent which replicate most readily in the new host species.

The epidemiology of BSE in cattle herds in Great Britain. I. Epidemiological processes, demography of cattle and approaches to control by culling

“…In experiments similar to those undertaken for scrapie, BSE was transmitted to mice from seven unrelated and geographically distant cattle hosts. The consistency of the pathology and incubation period observed for all seven BSE sources suggests that all seven were infected with the same strain of BSE (Fraser et al 1992;Bruce et al 1994;Bruce 1996).…”

“…Genetic studies of scrapie infection have identified two genes, the Sip and Sinc genes, which have a major influence on the duration of the incubation period (Dickinson et al 1968;Hunter et al 1992;Bruce et al 1994;Farquhar et al 1994). Experimental studies of scrapie have also indicated that some host genotypes appear to be resistant to infection (Davies & Kimberlin 1985;Foster & Dickinson 1988).…”

Prion agent diversity and species barrier

“…I). Strikingly, 301C and 301V were invariably obtained irrespectively of the species infected by the BSE agent, either accidentally (cats, exotic ruminants, humans) or experimentally (sheep, goats, pigs, macaques) [31,35,118]. It should be kept in mind, however, that the BSE agent underwent a single passage through the intermediate host.…”

“…In initial studies, transmission of various sources of infected cattle to a panel of inbred mice expressing the a or b mouse PrP allele (see section 3.4.1) suggested that cattle have been infected by a single strain since incubation periods and distribution of spongiosis in the brain were uniform in each genotype, unlike that seen with scrapie or CJD isolates [31,35,83]. The two agents propagated on a and b genotypes were termed 301C and 301V, respectively (Tab.…”

Current understanding of PrnP Genetics: A tool for Molecular Assisted Selection in Sheep Populations (A review)

“…Although for over 250 years there were no reported cases of transmission of classical scrapie to humans (Schneider et al, 2008), uncertainties related to the species barrier (Bruce et al, 1994) led many countries to develop policies to eliminate all animals infected with TSEs from the food chain (Heaton et al, 2011).…”