ARS | Publication request: Origins of BSE: evidence of sporadic and heritable BSE

Submitted to: United States-Japan Cooperative Program in Natural Resources
Publication Type: Abstract Only
Publication Acceptance Date: October 3, 2008
Publication Date: October 15, 2008
Citation: Nicholson, E.M., Brunelle, B.W., Kehrli, Jr., M.E., Greenlee, J.J. 2008. Origins of BSE: Evidence of Sporadic and Heritable BSE [abstract]. United States-Japan Cooperative Program in Natural Resources. p. 7.

Technical Abstract: Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) of cattle. Classical BSE is associated with ingestion of BSE-contaminated feedstuffs. H- and L-type BSE, collectively known as atypical BSE, differ from classical BSE by displaying a different disease phenotype and they have not been linked to the consumption of contaminated feed. Interestingly, the 2006 U.S. H-type atypical BSE animal had a polymorphism at codon 211 of the bovine prion gene resulting in a glutamic acid to lysine substitution (E211K). This substitution is analogous to the most prevalent form of heritable TSE in humans, and it is considered to have caused BSE in this animal. Sequence analysis revealed that both the 2006 U.S. atypical BSE animal and its 2-year-old heifer were heterozygous at bovine prion gene nucleotide 631. This single nucleotide polymorphism at codon 211 encodes GAA (glutamic acid) in one allele and AAA (lysine) in the other. Both animals carry the 211K polymorphism, indicating that the allele is heritable and may persist within the cattle population. Two regulatory region polymorphisms in the prion gene of cattle have been reported to have an association with resistance to classical BSE. However, our analysis revealed no association between genotype and resistance to atypical BSE or experimentally inoculated TSEs indicating that atypical BSE and experimentally inoculated TSEs are bypassing the site of influence of the polymorphisms. This genetic discrepancy demonstrates that atypical BSE progresses differently in the host relative to classical BSE, a result that is entirely consistent with the notion that atypical BSE originates spontaneously in cattle. Here we provide the first evidence that all 3 etiologic forms of TSEs (spontaneous, hereditary, and infectious) are present in a non-human species. Atypical BSE arising as both genetic and spontaneous disease, in the context of reports that at least some forms of atypical BSE can convert to classical BSE in mice, suggests a cattle origin for classical BSE.