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Title: Atypical BSE: role of the E211K prion polymorphism

item Greenlee, Justin

Submitted to: American Veterinary Medical Association Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 5/1/2013
Publication Date: 7/19/2013
Citation: Greenlee, J.J. 2013. Atypical BSE: role of the E211K prion polymorphism. 2013 American Veterinary Medical Association (AVMA) Annual Convention, July 19-23, 2013, Chicago, Illinois. Paper No. 13920. p. 45.

Interpretive Summary:

Technical Abstract: Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases that naturally affect several species including human beings. These chronic diseases are associated with the accumulation of a protease-resistant, disease-associated isoform of the prion protein (PrPSc) in the central nervous system and other tissues, depending on the species affected. In humans, TSEs can be acquired through exposure to infectious material, inherited as germline polymorphisms in the prion gene (prnp), or occur spontaneously. Bovine spongiform encephalopathy (BSE) or mad cow disease cases can be subclassified into at least 3 distinct disease forms with the predominant form known as classical BSE and the others collectively referred to as atypical BSE. Atypical BSE is further subdivided into H-type and L-type cases that are distinct from classical BSE and from each other on the basis of their unique molecular profiles. Both atypical BSE subtypes are believed to have arisen spontaneously and today researchers are investigating atypical BSE as a possible origin of classical BSE that was a feed-borne epidemic primarily affecting cattle in Europe where BSE-contaminated animal protein sources derived from central nervous system tissues were previously fed to ruminants. Several hypotheses have been proposed to explain atypical BSE cases. At the forefront of this discussion is the possibility that both H-type and L-type BSE may be spontaneous diseases in cattle. Support for atypical BSE occurring spontaneously is drawn from parallels to sporadic prion disease in humans, specifically, occurrence in older hosts and a comparable low incidence rate. Furthermore, atypical BSE occurs as isolated, sporadic cases in contrast to the clustering of cases observed for feedborne classical BSE. Recognition of a spontaneous prion disease in cattle, coupled with evidence indicating atypical BSE can convert to classical BSE upon serial passage in mice, has broad implications for our understanding of the origins of the classical form of the disease. In 2006 a critical discovery was made when one case of H-type BSE was associated with a heritable mutation in the prion protein gene referred to as E211K. This case was diagnosed in the U.S. and led to the identification of a new prion protein (prnp) allele, K211, that is associated with H-type BSE and is heritable. This presentation will present data demonstrating a rapid onset of disease in an animal with the E211K mutation following experimental inoculation with H-type BSE from the original E211K H-type BSE case. Interestingly, disease associated prion protein was widespread in neural tissues this animal, and antemortem retinal thinning and functional deficits of the visual system were observed prior to the onset of clinical disease. The existence of genetic forms of BSE offers new explanations for the potential origins of BSE.