Detection of Chronic Wasting Disease Prions in Salivary, Urinary, and Intestinal Tissues of Deer: Potential Mechanisms of Prion Shedding and Transmission
Haley, NJ and Mathiason, CK and Carver, SS and Zabel, M and Telling, GC and Hoover, EA, Detection of Chronic Wasting Disease Prions in Salivary, Urinary, and Intestinal Tissues of Deer: Potential Mechanisms of Prion Shedding and Transmission, Journal of Virology, 85, (13) pp. 6309-6318. ISSN 0022-538X (2011) [Refereed Article]
Efficient horizontal transmission is a signature trait of chronic wasting disease (CWD) in cervids.
Infectious prions shed into excreta appear to play a key role in this facile transmission, as has been
demonstrated by bioassays of cervid and transgenic species and serial protein misfolding cyclic amplification
(sPMCA). However, the source(s) of infectious prions in these body fluids has yet to be identified.
In the present study, we analyzed tissues proximate to saliva, urine, and fecal production by sPMCA in an
attempt to elucidate this unique aspect of CWD pathogenesis. Oropharyngeal, urogenital, and gastrointestinal
tissues along with blood and obex from CWD-exposed cervids (comprising 27 animals and >350
individual samples) were analyzed and scored based on the apparent relative CWD burden. PrPCWDgenerating
activity was detected in a range of tissues and was highest in the salivary gland, urinary
bladder, and distal intestinal tract. In the same assays, blood from the same animals and unseeded normal
brain homogenate controls (n 116 of 117) remained negative. The PrP-converting activity in peripheral
tissues varied from 1011- to 100-fold of that found in brain of the same animal. Deer with highest levels
of PrPCWD amplification in the brain had higher and more widely disseminated prion amplification in
excretory tissues. Interestingly, PrPCWD was not demonstrable in these excretory tissues by conventional
Western blotting, suggesting a low prion burden or the presence of protease-sensitive infectious prions
destroyed by harsh proteolytic treatments. These findings offer unique insights into the transmission of
CWD in particular and prion infection and trafficking overall.