Unique Properties of the Classical Bovine Spongiform Encephalopathy Strain and Its Emergence From H-Type Bovine Spongiform Encephalopathy Substantiated by VM Transmission Studies

Bencsik, Anna; Leboidre, Mikael; Debeer, Sabine; Aufauvre, Claire; Baron, Thierry

doi:10.1097/nen.0b013e318285c7f9

Cited by 21 publications

(23 citation statements)

References 30 publications

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“…These atypical BSE strains, which are rare (Ͻ100 cases identified worldwide), tend to affect older animals (23) and appear to represent sporadic forms of bovine prion diseases (24). Despite the apparent rarity of the various types of BSE, the facts that H-and L-BSE appear to arise spontaneously and have distinct transmissibilities (20,(25)(26)(27)(28)(29)(30)(31)(32) make it important to be able to detect and differentiate them to reduce the risk of transmission to cattle or other species, such as humans.…”

mentioning

confidence: 99%

Detection of Atypical H-Type Bovine Spongiform Encephalopathy and Discrimination of Bovine Prion Strains by Real-Time Quaking-Induced Conversion

et al. 2016

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Many mammalian species can be afflicted with prion diseases or transmissible spongiform encephalopathies. Prion diseases are neurodegenerative, transmissible, untreatable, and fatal (reviewed in references 1 and 2). The underlying pathogenesis of prion diseases involves the conversion of the host's normal prion protein, PrP C , to abnormal forms that are usually more protease resistant, multimeric, and insoluble. The multimeric and insoluble forms have been generically called PrP Sc (PrP-scrapie), or more functionally PrP Res (protease resistant) and PrP D (disease associated). At least some of these forms comprise the transmissible agent or prion (3-10). Multiple prion strains can be propagated within a given host species, giving consistently different clinical, pathological, and molecular phenotypes (11-16).The first prion disease to be recognized in cattle was classical bovine spongiform encephalopathy (C-BSE). C-BSE was likely caused primarily by widespread prion contamination of cattle feed (17). After peaking in the early 1990s, the incidence of C-BSE has now been greatly reduced by regulatory measures that limit its horizontal spread. C-BSE is the only known zoonotic prion disease, having caused variant Creutzfeldt-Jakob disease (vCJD) in humans who presumably consumed contaminated beef. Although new clinical cases of vCJD are rare (http://www.cjd.ed.ac .uk/documents/figs.pdf), a recent survey of appendices in the United Kingdom suggests a high incidence of subclinical vCJD infections, at ϳ1:2,000 of the population born between 1941 and 1985 (18).Since the C-BSE epidemic, two atypical strains of BSE, H-type BSE (H-BSE) and L-type BSE (L-BSE), have also been identified in cattle. PrPRes is usually composed of a mixture of glycosylated and unglycosylated molecules, and the various BSE strains can be differentiated biochemically using Western blotting of postmortem brain tissue samples by comparing the proteinase K (PK)-treated PrPRes banding patterns (19)(20)(21)(22). The H and L types of BSE are classified by their respective high and low apparent molecular masses of the unglycosylated PrP Res band. These atypical BSE strains, which are rare (Ͻ100 cases identified worldwide), tend to affect older animals (23) and appear to represent sporadic forms of bovine prion diseases (24). Despite the apparent rarity of the various types of BSE, the facts that H-and L-BSE appear to arise spontaneously and have distinct transmissibilities (20, 25-32) make it important to be able to detect and differentiate them to reduce the risk of transmission to cattle or other species, such as humans.Several in vitro methods have been developed to detect C-, L-, and H-BSE. Commercially available rapid immunochemical tests for PrP D can, in the best cases, give positive responses from 10 Ϫ3 to 10 Ϫ4 dilutions of postmortem brain tissues with high levels of PrP D (33, 34). Immunoblotting for PrP Res can detect BSE-infected tissues with similar sensitivity and also discriminate between the bovine strains based on the relative electro...

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confidence: 99%

Detection of Atypical H-Type Bovine Spongiform Encephalopathy and Discrimination of Bovine Prion Strains by Real-Time Quaking-Induced Conversion

et al. 2016

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“…There is evidence that, unlike classical BSE [49], L-BSE [20, 25, 42, 44, 45, 47], and H-BSE [21, 47, 50] do not always remain stable after intra- or inter-species experimental transmission. In some of these transmissions a phenotype shift from both L-BSE and H-BSE towards C-BSE has been reported [42, 47], on occasions only after sub-passage [25, 44, 45].…”

Section: Discussionmentioning

confidence: 99%

L-BSE experimentally transmitted to sheep presents as a unique disease phenotype

Simmons¹,

Chaplin²,

Konold

et al. 2016

Vet Res

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Apart from prion protein genotype, the factors determining the host range and susceptiblity for specific transmissible spongiform encephalopathy agents remain unclear. It is known that bovine atypical L-BSE can transmit to a range of species including primates and humanised transgenic mice. It is important, therefore, that there is as broad an understanding as possible of how such isolates might present in food animal species and how robust they are on inter- and intra-species transmission to inform surveillance sytems and risk assessments. This paper demonstrates that L-BSE can be intracerebrally transmitted to sheep of several genotypes, with the exception of ARR/ARR animals. Positive animals mostly present with a cataplectic form of disease characterized by collapsing episodes and reduced muscle tone. PrP accumulation is confined to the nervous system, with the exception of one animal with lymphoreticular involvement. In Western blot there was maintenance of the low molecular mass and glycoform profile associated with L-BSE, irrespective of ovine host genotype, but there was a substantially higher N-terminal antibody signal relative to the core-specific antibody, which is similar to the ratio associated with classical scrapie. The disease phenotype was maintained on experimental subpassage, but with a shortened survival time indicative of an original species barrier and subsequent adaptation. Passive surveillance approaches would be unlikely to identify such cases as TSE suspects, but current statutory active screening methods would be capable of detecting such cases and classifying them as unusual and requiring further investigation if they were to occur in the field.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-016-0394-1) contains supplementary material, which is available to authorized users.

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“…Wt mice are susceptible to classical BSE but much less to atypical BSE strains (27,28). In contrast, Bv109M voles were reported to be resistant to primary transmission with classical BSE, and transmission was apparent only after a blind second passage (9).…”

Section: Bv109m Prpmentioning

confidence: 99%

PrP ^C Governs Susceptibility to Prion Strains in Bank Vole, While Other Host Factors Modulate Strain Features

Espinosa

Nonno

Bari

et al. 2016

J Virol

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Bank vole is a rodent species that shows differential susceptibility to the experimental transmission of different prion strains. In this work, the transmission features of a panel of diverse prions with distinct origins were assayed both in bank vole expressing methionine at codon 109 (Bv109M) and in transgenic mice expressing physiological levels of bank vole PrP C (the BvPrP-Tg407 mouse line). This work is the first systematic comparison of the transmission features of a collection of prion isolates, representing a panel of diverse prion strains, in a transgenic-mouse model and in its natural counterpart. The results showed very similar transmission properties in both the natural species and the transgenic-mouse model, demonstrating the key role of the PrP amino acid sequence in prion transmission susceptibility. However, differences in the PrP Sc types propagated by Bv109M and BvPrP-Tg407 suggest that host factors other than PrP C modulate prion strain features. IMPORTANCEThe differential susceptibility of bank voles to prion strains can be modeled in transgenic mice, suggesting that this selective susceptibility is controlled by the vole PrP sequence alone rather than by other species-specific factors. Differences in the phenotypes observed after prion transmissions in bank voles and in the transgenic mice suggest that host factors other than the PrP C sequence may affect the selection of the substrain replicating in the animal model. Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of fatal neurodegenerative diseases that include Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, and scrapie in small ruminants. The prion agent consists mainly, if not entirely, of PrP Sc , which is an abnormal isoform of the host-encoded prion cellular protein, PrP C (1-4). Prion propagation is considered to occur in a two-step process in which aggregates of PrP Sc bind new PrP C monomers and then induce their conformational change into PrP Sc . The conversion into PrP Sc results in changes in physical properties, such as decreased solubility in nondenaturing detergents, an increase in ␤-pleated-sheet content, and increased resistance to proteolytic degradation.The occurrence of different TSE strains has been described in several species. Upon experimental transmission, TSE strains show distinctive incubation periods and neuropathological features that are maintained after subpassage in the same species. These strains correspond to different PrP Sc conformations, according to the prion hypothesis (5). Prion strain transmission among different species seems to be driven by the differences in the PrP amino acid sequences and by the prion strain being transmitted (6). Transgenic-mouse models null for the murine Prnp gene and expressing PrP C from another species (such as bovine, ovine, porcine, or human), have been used in the prion research field as useful tools to characterize prion strains and to learn about the susceptibility of the species t...

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Unique Properties of the Classical Bovine Spongiform Encephalopathy Strain and Its Emergence From H-Type Bovine Spongiform Encephalopathy Substantiated by VM Transmission Studies

Cited by 21 publications

References 30 publications

Detection of Atypical H-Type Bovine Spongiform Encephalopathy and Discrimination of Bovine Prion Strains by Real-Time Quaking-Induced Conversion

Detection of Atypical H-Type Bovine Spongiform Encephalopathy and Discrimination of Bovine Prion Strains by Real-Time Quaking-Induced Conversion

L-BSE experimentally transmitted to sheep presents as a unique disease phenotype

PrP ^C Governs Susceptibility to Prion Strains in Bank Vole, While Other Host Factors Modulate Strain Features

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Unique Properties of the Classical Bovine Spongiform Encephalopathy Strain and Its Emergence From H-Type Bovine Spongiform Encephalopathy Substantiated by VM Transmission Studies

Cited by 21 publications

References 30 publications

Detection of Atypical H-Type Bovine Spongiform Encephalopathy and Discrimination of Bovine Prion Strains by Real-Time Quaking-Induced Conversion

Detection of Atypical H-Type Bovine Spongiform Encephalopathy and Discrimination of Bovine Prion Strains by Real-Time Quaking-Induced Conversion

L-BSE experimentally transmitted to sheep presents as a unique disease phenotype

PrP C Governs Susceptibility to Prion Strains in Bank Vole, While Other Host Factors Modulate Strain Features

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PrP ^C Governs Susceptibility to Prion Strains in Bank Vole, While Other Host Factors Modulate Strain Features