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United States Department of Agriculture

Agricultural Research Service

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Title: Stability of PrP**Sc from cattle inoculated with different BSE strains

Authors
item Nicholson, Eric
item Vrentas, Catherine
item Greenlee, Justin

Submitted to: Protein Society Symposium
Publication Type: Abstract Only
Publication Acceptance Date: May 29, 2012
Publication Date: August 5, 2012
Citation: Nicholson, E.M., Vrentas, C.E., Greenlee, J.J. 2012. Stability of PrPSc from cattle inoculated with different BSE strains. 26th Annual Symposium of The Protein Society. p. 210.

Technical Abstract: Prion diseases are a class of transmissible neurodegenerative diseases, caused by an infectious protein, that afflict humans and other mammals. The infectious agent is a host encoded protein known as PrP that has adopted a misfolded conformation termed PrP**Sc. The diseases have been shown to manifest by 3 different pathologic processes including sporadic/spontaneous, genetic, and infectious. In addition to genetic origin of prion disease, differences in the prion gene (PRNP) have been shown to influence incubation time and in some cases confer near absolute resistance in instances of infectious transmission. Despite the protein only nature of the infectious agent, the various prion diseases exist in many different strains, which depending upon the strain, can be differentiated by tissue distribution, brain lesion profiles, as well as glycoform analysis and molecular weight profile using western blot. In rodent adapted models, prion strains have also been shown to confer differences in the stability of PrP**Sc as determined using GdmCl denaturation. In addition, PrP**Sc stability has been shown to correlate well with incubation time such that the shortest incubation times result from the least stable prion strains. In natural host species, a priori predictions of incubation time based upon an in vitro assay are relevant for studies of pathogenesis and holds practical implications for disease management. Toward this goal, we assess the stability of PrP**Sc derived from age matched Holstein steers inoculated with 3 different strains of Bovine Spongiform Encephalopathy (BSE) (H-type, L-type, and classical) as well as Transmissible Mink Encephalopathy (TME).* Each BSE strain is differentiable using glycoform analysis and molecular weight profile on a western blot, and the observed incubation time for TME, H-type BSE, and L-type BSE is considerably shorter than that for classical BSE. We compare the PrP**Sc stability determined using GdmCl unfolding of PrP**Sc monitored by ELISA to the observed incubation time. *All work was performed with the approval of the institutional review board of the sponsoring institution.

Last Modified: 12/20/2014
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