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Title: Intranasal inoculation of white-tailed deer (Odocoileus virginianus) with lyophilized chronic wasting disease prion particulate complexed to montmorillonite clay

Author
item NICHOLS, TRACY - Animal And Plant Health Inspection Service (APHIS)
item SPRAKER, T - Colorado State University
item RIGG, T - Animal And Plant Health Inspection Service (APHIS)
item MEYERETT-REID, C - Colorado State University
item HOOVER, C - Colorado State University
item MICHEL, B - Colorado State University
item BIAN, J - Colorado State University
item HOOVER, E - Colorado State University
item GIDLEWSKI, T - Animal And Plant Health Inspection Services (APHIS), National Wildlife Center
item BALACHANDRAN, A - Canadian Food Inspection Agency
item O'Rourke, Katherine
item TELLING, G - Colorado State University
item BOWEN, R - Colorado State University
item ZABEL, M - Colorado State University
item VERCAUTEREN, K - Animal And Plant Health Inspection Services (APHIS), National Wildlife Center

Submitted to: PLoS Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/21/2013
Publication Date: 5/9/2013
Citation: Nichols, T.A., Spraker, T.R., Rigg, T.D., Meyerett-Reid, C., Hoover, C., Michel, B., Bian, J., Hoover, E., Gidlewski, T., Balachandran, A., O'Rourke, K., Telling, G.C., Bowen, R., Zabel, M.D., Vercauteren, K.C. 2013. Intranasal inoculation of white-tailed deer (Odocoileus virginianus) with lyophilized chronic wasting disease prion particulate complexed to montmorillonite clay . PLoS Pathogens. DOI:10.1371/journal.pone.0062455.

Interpretive Summary: Chronic wasting disease is a fatal neurologic disease of deer and elk, characterized by accumulation of an abnormally folded form of the prion protein in the brain and lymph nodes. Control measures have failed to limit the gradual spread of the disease in wild and captive deer. Programs based on a better understanding of the routes of transmission might increase the efficiency of these measures. The objective of this study was to determine whether infectious prion particles adhered to dust particles could transmit the disease by the intranasal route. White tailed deer fawns were exposed by the nasal route to a dry powdered mixture of clay and prion-containing tissue extracts. Evidence of infection was observed in 10 of 11 inoculated deer as early as 94 days after the first exposure. A single change in the gene encoding the prion protein had a significant effect on amount of abnormal prion protein in the lymph nodes. The study suggests that the disease might be spread by inhalation of infected dust from contaminated premises and the genetic background of captive herds may alter the disease transmission patterns.

Technical Abstract: Chronic wasting disease (CWD) is the transmissible spongiform encephalopathy or TSE of deer and elk, occurring primarily in North America. The TSEs are fatal neurodegenerative disorders associated with conversion of a normal cell protein to a pathogenic and potentially infectious agent by post translational folding events. CWD is an infectious disease in which susceptibility and incubation time is associated with amino acid changes in the cellular prion protein. In white tailed deer, a glycine to serine substitution at residue 96 of the processed prion protein is associated with reduced rates of disease in captive and wild deer. The modes of transmission under field conditions are not known but appear to include both direct contact among animals and indirect transmission to naive animals exposed to infectious particles shed into the environment. Infectious prions are highly resistant to degradation by proteases, ultraviolet light and drying and are reported to bind tightly to certain soil particles. In this study, infectious prion extracts were bound to particles of montmorillonite clay, dessicated, and administered to white tailed deer fawns by the intranasal route. Ten of 11 inoculated deer developed evidence of infection, assessed by detection of abnormal prion proteins in lymphoid tissues. Infection was detected as early as 94 days after the first exposure and the extent of prion accumulation in nodes was related to the prion genotype at codon 96. This study demonstrated that inhalation of soil-bound prions may contribute to the spread of CWD and confirms earlier studies demonstrating that certain prion protein polymorphisms may have a significant effect on the pathogenesis of CWD in white tailed deer.