期刊
JOURNAL OF GENERAL VIROLOGY
卷 90, 期 -, 页码 1035-1047出版社
MICROBIOLOGY SOC
DOI: 10.1099/vir.0.007500-0
关键词
-
资金
- National Institutes of Health [AG02132, AG010770, A1064709]
- USDA Cooperative Agreement
- Schott Foundation
Chronic wasting disease (CWD) is a transmissible, fatal prion disease of cervids and is largely confined to North America. The origin of CWD continues to pose a conundrum: does the disease arise spontaneously or result from some other naturally occurring reservoir? To address whether prions from sheep might be able to cause disease in cervids, we inoculated mice expressing the elk prion protein (PrP) transgene [Tg(ElkPrP) mice] with two scrapie prion isolates. The SSBP/1 scrapie isolate transmitted disease to Tg(ElkPrP) mice with a median incubation time of 270 days, but a second isolate failed to produce neurological dysfunction in these mice. Although prions from cattle with bovine spongiform encephalopathy (BSE) did not transmit to the Tg(ElkPrP) mice, they did transmit after being passaged through sheep. In Tg(ElkPrP) mice, the sheep-passaged BSE prions exhibited an incubation time of approximately 300 days. SSBP/1 prions produced abundant deposits of the disease-causing PrP isoform, denoted PrPSc, in the cerebellum and pons of Tg(ElkPrP) mice, whereas PrPSc accumulation in Tg mice inoculated with sheep-passaged BSE prions was confined to the deep cerebellar nuclei, habenula and the brainstem. The susceptibility of 'cervidized' mice to 'ovinized' prions raises the question about why CWD has not been reported in other parts of the world where cervids and scrapie-infected sheep coexist.
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