Chronic Wasting Disease (CWD) is fatal neurodegeneterative disease of cervids caused by infectious proteins termed prions. Since identification in Colorado, the disease has spread to both free-ranging and captive cervids in 14 states and Canada, significantly impacting the hunting and captive cervid industries. CWD can have a high prevalence in captive herds, suggesting that it is efficiently transmitted between cervids. Controlled experiments in N. American deer and elk have been limited in scope due to the inherent difficulties in handling and confinement of large cervids. <P>The aim of this proposal is to develop a small deer model to study the pathogenesis and transmission of CWD in cervids. The Muntjac deer is a small cervid species that has been adapted to captivity and provides a viable alternative to the use of larger cervids to study the progression and transmission of CWD in a physiologically relevant model. In preliminary studies, muntjac deer were susceptible to CWD infection following oral inoculation. The goal of this proposal is to investigate the peripheral and central pathogenesis of CWD in muntjac deer following oral exposure. Establishment of a muntjac deer model for CWD would result in future applications aimed at investigating the peripheral spread of the CWD agent within a host and CWD transmission between cervids, with direct relevance to goals 3 and 5 of the CSREES Strategic Plan.
NON-TECHNICAL SUMMARY: Chronic Wasting Disease is a horizontally transmissible spongiform encephalopathy of free-ranging and captive cervids. To date, characterization of the transmission and pathogenesis of CWD has been difficult to study due to the lack of a small animal model. The goal of this proposal is to investigate the peripheral and central pathogenesis of CWD in muntjac deer following oral exposure.
APPROACH: The main goal of the proposed studies will be to investigate the peripheral and central pathogenesis of CWD in muntjac deer following oral exposure. Since muntjac deer are susceptible to CWD, two corollary aims will be pursued that will 1) investigate the role of migratory leukocyte subsets in the peripheral spread of the CWD agent, and 2) examine mucosal sites for CWD infection that are potential sites of agent shedding and/or transmission to naive hosts. The preliminary findings from these later two aims will form the basis of future proposal applications to the USDA in order to investigate the pathogenesis of CWD in cervids. <P> Aim 1. To investigate the temporal and spatial pattern of CWD infection in muntjac deer. Muntjac deer will be orally infected with the CWD agent and at 5, 10, 15, and 20 months postinfection the distribution of the CWD agent will be determined in lymphoid tissue and the nervous system using Western blot and immunohistochemistry in order to determine the early sites of CWD agent entry and spread in these tissues.<P> Aim 2. To define the role of peripheral blood leukocyte (PBL) subsets in the lymphoid spread of CWD. PBLs will be collected monthly from infected deer, fractionated by magnetic selection into T cells, B cells, and monocytes. At necropsy, the total blood volume will be collected from each animal and similarly fractionated. Pooled samples of leukocyte subets isolated from individual animals will be examined for the presence of the CWD agent by Western Blot. <P>Aim 3. To examine the mucosal distribution of the CWD agent in muntjac deer. Mucosal tissues that could be involved in CWD agent shedding will be collected from muntjac deer during the course of oral CWD infection will be examined for the presence of the CWD agent by Western blot and immunohistochemistry. These tissues include the cornea, olfactory sensory and non-sensory epithelium, vomeronasal olfactory epithelium, and the sensory tongue epithelium. <P>These preliminary studies could identify mucosal tissues that are a target for CWD infection and may represent sites for CWD agent shedding from infected hosts. These findings will be used to develop a more in-depth application to study CWD pathogenesis in order to define the route(s) of CWD agent shedding and transmission.