Location: Virus and Prion Research
Project Number: 5030-32000-114-000-D
Project Type: In-House Appropriated
Start Date: Oct 1, 2016
End Date: Sep 30, 2021
Objective:
Objective 1: Investigate the mechanisms of protein misfolding in prion disease, including the genetic determinants of misfolding of the prion protein, environmental influences on abnormal prion conversion, and environmental influences on protein misfolding as it relates to prion diseases.
Objective 2: Investigate the pathobiology of prion strains in natural hosts, including the influence of prion source genotype on interspecies transmission and the pathobiology of atypical transmissible spongiform encephalopathies (TSEs) and the presence of CWD prion strains in natural hosts by processing field samples through a strain identification program. Subobjective 2.A: Investigate the pathobiology of atypical TSEs. Subobjective 2.B: Investigate the influence of prion source genotype on interspecies transmission.
Objective 3: Investigate sampling methodologies for antemortem detection of prion disease, including the utility of blood sampling as a means to assess prion disease status of affected animals and the utility of environmental sampling for monitoring herd prion disease status. Subobjective 3.A: Investigate the utility of blood sampling as a means to assess prion disease status of affected animals. Subobjective 3.B: Investigate the utility of environmental sampling for monitoring herd prion disease status.
Objective 4: Determine the association of disease susceptibility or resistance with naturally occurring prion protein genotypes not yet associated with positive cases on infected premises, including genotype associated differences in prion accumulation and excretion, and develop a logic-based decision tree for CWD strain determination.
Objective 5: Develop improved live animal test for the detection of CWD-affected cervids, including a sensitive live animal test to detect CWD prions in individual animals, a sensitive live animal screening test for the purpose of determining a herd’s CWD status, and a sensitive deployable CWD test for use by State diagnostic labs.
Approach:
The studies will focus on three animal transmissible spongiform encephalopathy (TSE) agents found in the United States: bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; and chronic wasting disease (CWD) of deer, elk, and moose. The research will address sites of protein folding and misfolding as it relates to prion disease, accumulation of misfolded protein in the host, routes of infection, and ante mortem diagnostics with an emphasis on controlled conditions and natural routes of infection. Techniques used will include spectroscopic monitoring of protein folding/misfolding, clinical exams, histopathology, immunohistochemistry, and biochemical analysis of proteins. The enhanced knowledge gained from this work will help understand the underlying mechanisms of prion disease and mitigate the potential for unrecognized epidemic expansions of these diseases in populations of animals that could either directly or indirectly affect food animals.
