Abstract
Chronic wasting disease (CWD) is a prion disease affecting captive and free-ranging cervids (e.g. deer, elk, and moose). The mechanisms of CWD transmission are poorly understood, though bodily fluids are thought to play an important role. Here we report the presence of infectious prions in the urine and saliva of deer with chronic wasting disease (CWD). Prion infectivity was detected by bioassay of concentrated, dialyzed urine and saliva in transgenic mice expressing the cervid PrP gene (Tg[CerPrP] mice). In addition, PrPCWD was detected in pooled and concentrated urine by protein misfolding cyclic amplification (PMCA). The concentration of abnormal prion protein in bodily fluids was very low, as indicated by: undetectable PrPCWD levels by traditional assays (western blot, ELISA) and prolonged incubation periods and incomplete TSE attack rates in inoculated Tg(CerPrP) mice (373±3days in 2 of 9 urine-inoculated mice and 342±109 days in 8 of 9 saliva-inoculated mice). These findings help extend our understanding of CWD prion shedding and transmission and portend the detection of infectious prions in body fluids in other prion infections.
Highlights
Chronic wasting disease (CWD) is an efficiently transmitted prion disease of cervids and is the only prion disease affecting free-ranging, non-domestic animals
To investigate whether urine may play a role in natural CWD transmission, and to confirm the presence of PrPCWD in saliva, we pooled and concentrated urine or saliva from five terminally infected CWD+ deer and inoculated two groups of tg1536 mice
Central nervous system tissues were evaluated for PrPCWD using western blotting (WB), immunohistochemistry (IHC) and, when negative by conventional assays, protein misfolding cyclic amplification (PMCA)
Summary
Chronic wasting disease (CWD) is an efficiently transmitted prion disease of cervids (e.g. deer, elk, and moose) and is the only prion disease affecting free-ranging, non-domestic animals. CWD has been identified in captive and free-ranging cervids in 15 states, 2 Canadian provinces, and Korea [3]. As surveillance efforts have intensified, CWD has been detected in areas previously thought to be free of infection, including recent discoveries in West Virginia, New York, and Michigan. The mechanisms of CWD transmission are not well understood, there is evidence that infection is transmitted horizontally and can be acquired from environmental sources [5,6], which underlies the assumption that shedding of infectious prions must be significant. Because of an apparently strong species barrier [7] and the as yet incompletely understood natural routes and kinetics of CWD transmission, the magnitude and consequence of this exposure remain speculative
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