Strain-Specific Barriers against Bovine Prions in Hamsters

Nicot, Simon; Baron, Thierry

doi:10.1128/jvi.01872-10

Cited by 27 publications

(28 citation statements)

References 21 publications

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“…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]. Such phenotype shifts have also been observed with other animal TSEs [46, 51].…”

Section: Discussionmentioning

confidence: 88%

“…These include cattle [36–39], sheep [40–42] and this report, lemurs [43], macaques [23, 24], hamsters [25, 44, 45] and transgenic mice overexpressing bovine, ovine or human PrP [20, 25–27, 39, 42, 44, 46–48]. In contrast to classical BSE, L-BSE does not transmit to wild type [20] Spiropoulos and Simmons, unpublished data] or transgenic mice that overexpress murine PrP [45, 47], although exceptions have been reported [20].…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Simmons¹,

Chaplin²,

Konold

et al. 2016

Vet Res

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“…Further concerns about the atypical BSE strains have arisen from observations that nonhuman primates and transgenic mice expressing human PrP Sen show differing susceptibilities to C-BSE and L-BSE (11-16). Although controversial (16), some findings suggest that L-BSE has greater pathogenicity than C-BSE in transgenic mice and Syrian golden hamsters (10,17,18). Furthermore, L-BSE prions have been shown to be experimentally transmissible to cattle (19,20) and transgenic mice overexpressing bovine or human prion protein (PrP) (21-23) with shorter incubation periods and more severe spongiform changes than C-BSE prions.…”

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confidence: 99%

Detection and Discrimination of Classical and Atypical L-Type Bovine Spongiform Encephalopathy by Real-Time Quaking-Induced Conversion

et al. 2015

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Statutory surveillance of bovine spongiform encephalopathy (BSE) indicates that cattle are susceptible to both classical BSE (C-BSE) and atypical forms of BSE. Atypical forms of BSE appear to be sporadic and thus may never be eradicated. A major challenge for prion surveillance is the lack of sufficiently practical and sensitive tests for routine BSE detection and strain discrimination. The real-time quaking-induced conversion (RT-QuIC) test, which is based on prion-seeded fibrillization of recombinant prion protein (rPrP Sen ), is known to be highly specific and sensitive for the detection of multiple human and animal prion diseases but not BSE. Here, we tested brain tissue from cattle affected by C-BSE and atypical L-type bovine spongiform encephalopathy (L-type BSE or L-BSE) with the RT-QuIC assay and found that both BSE forms can be detected and distinguished using particular rPrP Sen substrates. Specifically, L-BSE was detected using multiple rPrP Sen substrates, while C-BSE was much more selective. This substrate-based approach suggests a diagnostic strategy for specific, sensitive, and rapid detection and discrimination of at least some BSE forms.T ransmissible spongiform encephalopathies (TSEs), or prion diseases, such as Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform encephalopathy (BSE) in cattle, are fatal neurodegenerative disorders characterized by spongiosis, neuronal loss, gliosis, and abnormal deposition of host-encoded prion protein (PrP) in the brain. The infectious agent responsible for TSEs appears to be largely composed of a misfolded and multimeric form of prion protein (PrP Sc ), which is able to induce polymerization and conformational conversion of normal proteasesensitive prion protein (PrP Sen ) into PrP Sc and its partially protease-resistant forms (PrP Res ) (1). BSE and its link to variant Creutzfeldt-Jakob disease (vCJD) in humans have raised important food safety issues. The incidence of classical BSE (C-BSE) has decreased as a result of disease-control programs, such as the ruminant feed ban (2). However, atypical forms of bovine prion disease have been identified in several countries (3). These emerging bovine prion strains can be categorized as H-type BSE (H-BSE) or L-type BSE (L-BSE or bovine amyloidotic spongiform encephalopathy [BASE] when amyloid plaques are present in the brain). These atypical BSE strains are differentiated biochemically by the electrophoretic mobility and glycoform pattern of PrP Res after proteinase K (PK) digestion (4-7). Currently, both of these atypical bovine prion strains, which mainly affect older animals (8), are thought to be sporadic forms of bovine prion diseases (9) and are still rare (less than 100 cases identified worldwide to date).It is suspected that one of these atypical L-BSE or H-BSE strains may have instigated the C-BSE epidemic, as suggested, for example, by the fact that the L-BSE strain can convert to C-BSE following serial passage in mice (5,6,10). Further concerns about the atypical BSE strains have arisen from...

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“…On first passage, all inoculated animals either remain asymptomatic for extended periods (3)(4)(5)(6)(7)(8)(9) or may develop disease after a prolonged asymptomatic phase (8,10,11). In a third alternative, only a subpopulation develops disease, with variable incubation times (8,12,13).…”

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confidence: 99%

Prion replication without host adaptation during interspecies transmissions

Bian

Khaychuk

Angers

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Adaptation of prions to new species is thought to reflect the capacity of the host-encoded cellular form of the prion protein (PrPC) to selectively propagate optimized prion conformations from larger ensembles generated in the species of origin. Here we describe an alternate replicative process, termed nonadaptive prion amplification (NAPA), in which dominant conformers bypass this requirement during particular interspecies transmissions. To model susceptibility of horses to prions, we produced transgenic (Tg) mice expressing cognate PrPC. Although disease transmission to only a subset of infected TgEq indicated a significant barrier to EqPrPCconversion, the resulting horse prions unexpectedly failed to cause disease upon further passage to TgEq. TgD expressing deer PrPCwas similarly refractory to deer prions from diseased TgD infected with mink prions. In both cases, the resulting prions transmitted to mice expressing PrPCfrom the species of prion origin, demonstrating that transmission barrier eradication of the originating prions was ephemeral and adaptation superficial in TgEq and TgD. Horse prions produced in vitro by protein misfolding cyclic amplification of mouse prions using horse PrPCalso failed to infect TgEq but retained tropism for wild-type mice. Concordant patterns of neuropathology and prion deposition in susceptible mice infected with NAPA prions and the corresponding prion of origin confirmed preservation of strain properties. The comparable responses of both prion types to guanidine hydrochloride denaturation indicated this occurs because NAPA precludes selection of novel prion conformations. Our findings provide insights into mechanisms regulating interspecies prion transmission and a framework to reconcile puzzling epidemiological features of certain prion disorders.

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Strain-Specific Barriers against Bovine Prions in Hamsters

Cited by 27 publications

References 21 publications

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

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

Detection and Discrimination of Classical and Atypical L-Type Bovine Spongiform Encephalopathy by Real-Time Quaking-Induced Conversion

Prion replication without host adaptation during interspecies transmissions

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