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They propose three aims which explore basic issues in prion biology: <ol> <li>Aim 1 seeks to identify PrPres bearing cell phenotypes in lymphoid tissues by using established PrPres specific dual immunohisto/cytochemistry and dual signal amplified immunofluorescence assays.
<li>A small animal alternative host which recapitulates the alimentary and lymphoid phases of nvCJD/CWD would be valuable to assess PrPres trafficking routes in vivo and for antemortem assay development. In aim 2 therefore they will expose ferrets to infectious CWD prions orally and determine by sequential sampling whether PrPres is detectable in lymphoid tissues and blood.
<li>Relatively little is known of the initial prion pathways to lymphoid tissue or the CNS. In aim 3 they will use PrPres specific antibodies, flow cytometry, dual immunostaining and in vivo infectivity to seek potential cell vectors for prion dissemination in blood and lymph in CWD infected deer and ferrets. Detection of PrPres in the blood has significant implications for blood and plasma transfusion.</ol>
Early prion protein accumulation in lymphoid tissues is an intriguing and likely important feature of several TSE including scrapie in sheep, CWD in deer and nvCJD in humans. Understanding prion entry, trafficking and neuroinvasion is critical for development of diagnostic and intervention strategies. The investigators propose to study CWD of deer as a model of nvCJD/prion pathogenesis. CWD PrPres is abundant in lymphoid tissue of infected deer and therefore may potentially be more readily detected in blood and circulating leukocytes.
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The results of these studies will contribute to understanding PrP trafficking in the lymphoid system and could provide a basis for development of diagnostic and intervention strategies.</p>