Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt-Jakob disease

Abstract

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are mammalian neurodegenerative disorders characterized by a posttranslational conversion and brain accumulation of an insoluble, protease-resistant isoform (PrP Sc ) of the host-encoded cellular prion protein (PrP C ). Human and animal TSE agents exist as different phenotypes that can be biochemically differentiated on the basis of the molecular mass of the protease-resistant PrP Sc fragments and the degree of glycosylation. Epidemiological, molecular, and transmission studies strongly suggest that the single strain of agent responsible for bovine spongiform encephalopathy (BSE) has infected humans, causing variant Creutzfeldt-Jakob disease. The unprecedented biological properties of the BSE agent, which circumvents the so-called ''species barrier'' between cattle and humans and adapts to different mammalian species, has raised considerable concern for human health. To date, it is unknown whether more than one strain might be responsible for cattle TSE or whether the BSE agent undergoes phenotypic variation after natural transmission. Here we provide evidence of a second cattle TSE. The disorder was pathologically characterized by the presence of PrP-immunopositive amyloid plaques, as opposed to the lack of amyloid deposition in typical BSE cases, and by a different pattern of regional distribution and topology of brain PrP Sc accumulation. In addition, Western blot analysis showed a PrP Sc type with predominance of the low molecular mass glycoform and a protease-resistant fragment of lower molecular mass than BSE-PrP Sc . Strikingly, the molecular signature of this previously undescribed bovine PrP Sc was similar to that encountered in a distinct subtype of sporadic Creutzfeldt-Jakob disease.

Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and L-type Bovine Spongiform Encephalopathy in a Mouse Model

“…A similar low-molecular-mass PrP res profile has been observed in L-type BSE or BASE ( 11 , 13 , 16 ), and in the current study, these similar PrP res molecular properties between bovine TME and L-type BSE were demonstrated in TgOvPrP4 mice. These 2 distinct bovine TSE sources were both readily transmitted into TgOvPrP4 mice (illustrating the usefulness of transgenic mouse models for prion agent strain typing when transmission to a common wild-type rodent is not possible) and had several common features including survival periods, PrP res molecular features, and the distribution of vacuolar pathologic changes.…”

Prion agent diversity and species barrier

“…In addition to the L-type group already mentioned (see Sect. 3.3.2), which has been identified in France [28], Italy [47], Germany [42] and Poland [151], a second group termed H-type has been found. Its PrP res signature is characterized by protease-resistant fragments of an increased size and a different glycopattern as compared to BSE [27].…”

“…Variant CJD agent may also occasionally undergo a strain shift on transmission to humanized mice, leading to sporadic CJD-like strain in a proportion of mice [22]. slightly lower molecular size and a different glycopattern, and a tendency to form amyloid plaques in cattle brain ( [27,42,47] and Sect. 5.2).…”

A prion disease of cervids: Chronic wasting disease

“…Human susceptibility to CWD or to other newly emerging animal TSE [9,14] is still unclear, although we can be somewhat reassured in that there have been no large scale outbreaks of human TSE cases in Colorado and Wyoming, where CWD has existed for decades [51]. Up until approximately 10 years ago, autopsies were not performed on suspect human TSE cases in many states due to biosafety concerns, therefore the diagnosis of potential new TSE strains has been hampered.…”