Species Barriers to Prion Transmission

There are some differences between species in the normal PrP sequence. There are also differences within a single species. These differences present some barrier to PrP^sc formation, with the greater the difference the greater the barrier. But, sufficient exposure can apparently overcome the barrier in many cases.

The extent to which prion diseases can cross species barriers depends on several factors. These include strain of the prion, dose of the prion, genetics of the target individual within a species, and method of introduction (Oral vs. Systemic vs. Intracerebral vs. Conjunctival).

Whether or not a host is susceptible to prion infection is determined by both the prion inoculum (source and dose) and the PrP gene. For example, a single mouse prion isolate will produce disease after varying incubation times which depend on the mouse strain. When prions are transmitted from one species to another, the initial incubation period (if transmission occurs) is very long. As the prion disease is continually passed in the new species, the incubation becomes shorter eventually stabilizing.

The species barrier can be "overcome" if a transgene from the prion donor can be introduced into the recipient species.

While human and animal prion disease have been experimentally transmitted to various monkey species, spontaneous occurrence of a spongiform encephalopathy in non-human primates has not been reported until recently. Bons et al. (1996) reported that in the 1991 a previously healthy rhesus monkey became lethargic, developed mood changes (aggressiveness) and hid from its companions. The brain of this monkey spongiform changes and large vacuoles in the neurons. Immunohistochemistry showed distended nerve-cell processes surrounded with PrP-immunoreactive material similar to that seen in squirrel monkeys inoculated with brain material from patients with CJD (Lancet 24:435-38). Immunological labeling of neurons in this monkey resembled those seen in the brains of patients with CJD (Neurodegeneration 4:357-68).

A breeding colony (n = 100) of marmosets in the UK were fed pellets containing 20% ruminant-derived meat-meal protein from 1985 to 1996. Adults weighing about 350 g ingested about 2 g meat meal/d. Over their 5-15 life spans, histopathological evaluation of brains revealed no evidence of neurodegenerative change (Ridley et al., 1996). (Level of contamination of the meal diet with BSE infective materials was unknown.)