ORCID Profile
0000-0002-5920-4556
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Publisher: American Society for Microbiology
Date: 07-2011
DOI: 10.1128/JVI.00425-11
Abstract: 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 lification (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 in idual s les) were analyzed and scored based on the apparent relative CWD burden. PrP CWD -generating 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 10 −11 - to 10 0 -fold of that found in brain of the same animal. Deer with highest levels of PrP CWD lification in the brain had higher and more widely disseminated prion lification in excretory tissues. Interestingly, PrP CWD 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.
Publisher: Microbiology Society
Date: 05-2012
Abstract: As the only prion disease affecting free-ranging animals, ante-mortem identification of affected cervids has become paramount in understanding chronic wasting disease (CWD) pathogenesis, prevalence and control of horizontal or vertical transmission. To seek maximal sensitivity in ante-mortem detection of CWD infection, this study used paired tonsil biopsy s les collected at various time points from 48 CWD-exposed cervids to compare blinded serial protein misfolding cyclic lification (sPMCA) with the assay long considered the ‘gold standard’ for CWD detection, immunohistochemistry (IHC). sPMCA-negative controls (34 % of the s les evaluated) included tissues from mock-inoculated animals and unspiked negative controls, all of which tested negative throughout the course of the study. It was found that sPMCA on tonsil biopsies detected CWD infection significantly earlier (2.78 months, 95 % confidence interval 2.40–3.15) than conventional IHC. Interestingly, a correlation was observed between early detection by sPMCA and host PRNP genotype. These findings demonstrate that in vitro - lification assays provide enhanced sensitivity and advanced detection of CWD infection in the peripheral tissues of cervids, with a potential role for spike or substrate genotype in sPMCA lification efficiency.
Publisher: Public Library of Science (PLoS)
Date: 25-11-2013
No related grants have been discovered for Candace Mathiason.