Abstract
Experimental and epidemiological evidence indicates that bovine spongiform encephalopathy (BSE) has been transmitted to humans1,2,3,4 although the mechanism of this transmission is unknown. Hamsters and chickens are clinically resistant to the transmission of BSE, but we report results that raise concern over the possible long-term persistence of infectivity in such clinically resistant species and which may have implications for the control of BSE.
Main
‘Natural’ transmission of BSE seems to result mainly, if not solely, from feeding animals with meat and bonemeal derived from BSE-infected cattle5. BSE is transmissible by inoculation or ingestion to mice, sheep, goats, marmosets, mink, pigs, certain members of the cat family and various exotic ungulates.
Interestingly, though, it is not transmissible to hamsters or chickens5. This resistance to BSE is borne out by an absence of clinical brain disease and a lack of the hallmark protease-resistant prion protein.
We injected 107 ID50 (where ID50 is the half-maximal infectious dose) units of hamster scrapie agent (strain 263K) into the brains of groups of C57BL/10 mice that either did or did not express the mouse gene that encodes the normal version of the prion protein (PrP). Mice are highly resistant to this hamster scrapie strain6 and, as expected, none of our mice developed any clinical symptoms of scrapie.
We found, however, that brain and spleen tissue from the PrP-positive mice obtained between 204 and 782 days after inoculation contained scrapie agent that was capable of infecting hamsters but not mice (Table 1). All of the recipient hamsters were positive, although the long incubation periods indicated that the amount of infectivity present was about 102 ID50 per gram of tissue, far lower than is typically found in clinical scrapie in hamsters or mice.
By contrast, tissues of mice without a functional PrP gene (PrPo/omice) were only very rarely able to transmit disease to recipient hamsters. Thus, expression of a normal mouse PrP gene seemed to enable hamster scrapie agent to persist in the brains and spleens of normal mice, suggesting that perhaps mouse PrP could be functioning as a receptor for the infectious agent4. However, there was no evidence for any replication of the hamster scrapie agent in these persistently infected mice. The infectivity recovered remained specific for hamsters rather than mice (Table 1).
Although we have not tested whether similar results would be obtained after oral ingestion, this unexpected and prolonged survival of a foreign scrapie agent raises the possibility that BSE infectivity might persist in various ‘resistant’ species exposed to BSE-contaminated feeds. Of particular concern would be domestic animals such as poultry which are raised for human consumption.
So far, there is no evidence for the secondary transmission of BSE from such resistant species to more susceptible species. However, the results presented here would strongly favour a decision to stop feeding ruminant-derived products to all animal species. Additional experiments should be carried out to detect possible BSE infectivity in clinically normal BSE-exposed animal species. Titration in cattle may be necessary to achieve the sensitivity needed to detect the levels of BSE anticipated in such situations.
References
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Race, R., Chesebro, B. Scrapie infectivity found in resistant species. Nature 392, 770 (1998). https://doi.org/10.1038/33834
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DOI: https://doi.org/10.1038/33834
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