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Tracking infectious prions in the body fluids of deer infected with chronic wasting disease

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dc.contributor.authorMathiason, Candace Kay, author
dc.contributor.authorHoover, Edward A., advisor
dc.contributor.authorAvery, Anne, committee member
dc.contributor.authorBamburg, James R., committee member
dc.contributor.authorZabel, Mark, committee member
dc.date.accessioned2022-07-01T00:08:24Z
dc.date.available2022-07-01T00:08:24Z
dc.date.issued2010
dc.description.abstractChronic wasting disease (CWD) is a prion disease of cervid (elk, moose and deer) with unusually high transmission efficiency. While the nidus of disease was described in a captive herd of cervid in northern Colorado/southeastern Wyoming in the late 60's, it has now been detected in both captive and free-ranging populations in 17 states and 2 Canadian provinces of North America and one Asian country. CWD is unique in being the only transmissible spongiform encephalopathy (TSE) described in a free-ranging population of animals. The etiology of CWD, like all prion diseases, is the conversion of the normal host-encoded cellular prion protein (PrPC) to an aberrantly folded protease resistant isoform (PrPRES/PrPCWD). An intriguing aspect of prion diseases is their ability to be transmitted from one organism to the next. In this dissertation work, we ask-By what means are infectious prions transmitted from one host to the next? In particular to CWD-What do infected cervids share or leave behind that contain sufficient infectious particles to initiate disease in the next cervid? We addressed this question by bioassay of body secretions and excretions- ' secreta '- (saliva, blood, urine and feces) in the native white-tailed deer host and in transgenic mice expressing the normal cervid prion protein (Tg(CerPrP) mice). Cohorts of deer were exposed by oral (PO) ingestion of 'secreta', or intraperitoneal (IP)/intravenous (IV) transfusion of blood components. To replicate a more natural/realistic exposure to CWD in which a deer might travel into a contaminated area and feed for a short period of time, an additional cohort of deer was exposed to fomites (bedding, feed and water buckets) from the suites of CWD-infected deer-without direct contact with infected deer. These variously exposed deer were monitored for a minimum of 19 months post inoculation (mo pi) for CWD infection and disease by immunohistochemical (IHC) and western blot (WB) detection of PrPCWD in serial tonsil biopsies and in multiple tissues after necropsy. Parallel studies were conducted in Tg(CerPrP) mice with the addition of an intracranial (IC) inoculation group for each body fluid. We found that sufficient infectious prions were present in the saliva, whole blood, the B cell- and platelet-enriched fractions of blood, and in fomites from infected deer premises to transmit CWD. Conversely, PrPCWD was not detected in the brain or lymphoid tissues of deer or mice inoculated with urine and feces, cell-free plasma or CD14+ monocytes from CWD-infected donor deer. The results of this work: 1) suggest that the efficient transmission of CWD may be due in part to the sharing of saliva between cervids and its deposition upon surfaces frequented by cervids; 2) establish a hematogenous dissemination of infectious prions in CWD associated with the cellular fraction of blood- in particular B cells and platelets— in CWD-infected deer; 3) extend previous work localizing PrPCWD to the interface of follicular B cells and dendritic cells; 4) provide insights to PrPCWD trafficking and CWD pathogenesis; and 5) establish saliva and blood cells as viable substrates for PrPCWD antemortem detection.
dc.format.mediumdoctoral dissertations
dc.identifier.urihttps://hdl.handle.net/10217/235400
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relationCatalog record number (MMS ID): 991014246289703361
dc.relationSF997.5.C46.M375 2010
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subject.lcshChronic wasting disease
dc.subject.lcshPrion diseases in animals
dc.subject.lcshDeer -- Diseases
dc.titleTracking infectious prions in the body fluids of deer infected with chronic wasting disease
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineMicrobiology, Immunology and Pathology
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D)

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