Chronic wasting disease (CWD), an emergent, efficiently transmitted, fatal prion disease of cervids (deer, elk, moose), is now identified in 15 states, 2 Canadian provinces, and Korea. We have found that infectious prions capable of transmitting CWD are present in the saliva, blood, and urine of CWD-infected deer, potentially explaining the lateral transmission of the disease. The presence of CWD prions in saliva and blood confirms prion infectivity in biological fluids and provides realistic hope for antemortem detection via a more sensitive in vitro assay, which forms the basis for this application. Direct detection of the abnormal CWD prion protein (PrPRES/CWD) in body fluids or excreta of deer has not been possible using contemporary assay methodologies (i.e. immunohistochemistry, western blotting, ELISA). Here we propose to employ serial protein misfolding cyclic amplification (sPMCA) to amplify and detect PrPCWD in saliva, blood, urine, and feces of infected deer. Direct in vitro detection of PrPCWD would enable pre-symptomatic ante-mortem diagnosis, improve ecologic understanding of CWD, and potentially enable detection of prion carrier states and contamination in cervid products. Whether a non-cervid reservoir for CWD infection exists in nature remains unknown. Likewise, whether CWD represents a risk to human health is uncertain. To begin to assess the potential for trans-species transmission of CWD, we propose to use sPMCA as a surrogate to assess whether the normal prion protein from selected non-cervid species can be converted to the abnormal PrPCWD isoform after exposure to CWD prions. This information will be used to direct correlative in vivo inoculation and epidemiologic studies needed to assess the CWD species barrier, identify potential reservoir hosts in nature, and better estimate potential human or other species health risks posed by CWD.

Public Health Relevance

Chronic wasting disease (CWD) is a rapidly spreading fatal prion disease of deer and elk, probably spread through saliva, and now present in 15 states. Whether CWD may represent a risk to human health analogous to mad cow disease is unknown. Proposed here is a new more powerful test to detect CWD prions in saliva, blood, and excretions of infected deer-something not possible with current technology yet vital to controlling the spread of CWD among deer and potentially other species.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS061902-01A2
Application #
7779776
Study Section
Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)
Program Officer
Wong, May
Project Start
2009-09-30
Project End
2012-07-31
Budget Start
2009-09-30
Budget End
2010-07-31
Support Year
1
Fiscal Year
2009
Total Cost
$310,204
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Microbiology/Immun/Virology
Type
Schools of Veterinary Medicine
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
Davenport, Kristen A; Henderson, Davin M; Mathiason, Candace K et al. (2016) Assessment of the PrPc Amino-Terminal Domain in Prion Species Barriers. J Virol 90:10752-10761
Hoover, Clare E; Davenport, Kristen A; Henderson, Davin M et al. (2016) Detection and Quantification of CWD Prions in Fixed Paraffin Embedded Tissues by Real-Time Quaking-Induced Conversion. Sci Rep 6:25098
Pritzkow, Sandra; Morales, Rodrigo; Moda, Fabio et al. (2015) Grass plants bind, retain, uptake, and transport infectious prions. Cell Rep 11:1168-75
Seelig, D M; Nalls, A V; Flasik, M et al. (2015) Lesion profiling and subcellular prion localization of cervid chronic wasting disease in domestic cats. Vet Pathol 52:107-19
Henderson, Davin M; Davenport, Kristen A; Haley, Nicholas J et al. (2015) Quantitative assessment of prion infectivity in tissues and body fluids by real-time quaking-induced conversion. J Gen Virol 96:210-9
Haley, Nicholas J; Hoover, Edward A (2015) Chronic wasting disease of cervids: current knowledge and future perspectives. Annu Rev Anim Biosci 3:305-25
Davenport, Kristen A; Henderson, Davin M; Bian, Jifeng et al. (2015) Insights into Chronic Wasting Disease and Bovine Spongiform Encephalopathy Species Barriers by Use of Real-Time Conversion. J Virol 89:9524-31
Henderson, Davin M; Denkers, Nathaniel D; Hoover, Clare E et al. (2015) Longitudinal Detection of Prion Shedding in Saliva and Urine by Chronic Wasting Disease-Infected Deer by Real-Time Quaking-Induced Conversion. J Virol 89:9338-47
Haley, Nicholas J; Carver, Scott; Hoon-Hanks, Laura L et al. (2014) Detection of chronic wasting disease in the lymph nodes of free-ranging cervids by real-time quaking-induced conversion. J Clin Microbiol 52:3237-43
Perrott, Matthew R; Sigurdson, Christina J; Mason, Gary L et al. (2013) Mucosal transmission and pathogenesis of chronic wasting disease in ferrets. J Gen Virol 94:432-42

Showing the most recent 10 out of 16 publications