Prion diseases transmission barriers

Prion transmission between species is limited by a barrier. A species barrier restricts transmission of prion disease between different mammalian species. On primary passage of prions from species A to species B, usually not all inoculated animals of species B develop disease, and those that do have much longer and more variable incubation periods than those that are seen with transmission of prions within the same species. On second passage of infectivity to further animals of the species B, transmission parameters resemble within-species transmissions, with most if not all animals developing the disease with short and consistent incubation periods. Species barriers can therefore be quantified by measuring the fall... 

After our protofibril model was shown to be plausible, similar models were built for WT hamster, human, and bovine PrP [121]. Again, the initial monomer structure was obtained from MD simulation at the strongly acidic pH regime. In contrast to hamster PrP, human and bovine PrP showed a left-handed spiral formation (Fig. 3b). This difference and further subtle differences between the individual protofibril models may reflect strain differences and give clues to the origin of observed species barriers [122] transmission of prion disease between different species can be inefficient or even absent. Furthermore, the models may help to... 

Early experimental transmission studies of human prion diseases were mainly done in laboratory primates, in particular chimpanzees and squirrel monkeys (Brown et al, 1994). These early transmission studies had rather long incubation periods, were expensive, and attracted ethical concerns. Primary transmission of human prions to wild-type laboratory mice have also been fairly unsuccessful, with only occasional transmissions occurring and then at prolonged incubation periods, close to the natural life span of the mice. This difficulty in primary transmissions is the concept of species barrier (Pattison and Jones, 1968), the principal determinants of which appear to be degree of homology between the host and the inoculum (Prusiner et al, 1990) and the strain of disease agent. 

However, it appears that not all TSEs are transferable to all species. Scrapie disease in sheep is not known to be infectious in humans, although it seems infectious in cows. Thus, there appear to be species barriers to infectivity. The potential infectivity of CWD disease to humans is not known, although testing of game animals taken by hunters in the CWD-infected areas has been encouraged. The mechanism for the horizontal spread of CWD in deer and elk is without explanation, and it is not clear if transmission to humans is possible, or what the disease would look like if it were transmitted (Xie et al., 2006). It is intriguing to speculate that prion infectivity could leap from one species to another nonpermissible species by way of a permissible intermediate, possibly as evidenced by sheep scrapie to mad cow to human vCJD. 

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