<i>In vitro</i> amplification of H-type atypical bovine spongiform encephalopathy by protein misfolding cyclic amplification

O’Connor, Matthew J; Bishop, Keith; Workman, Robert G.; Maddison, Ben C.; Gough, Kevin C.

doi:10.1080/19336896.2016.1259051

Cited by 4 publications

(3 citation statements)

References 26 publications

(33 reference statements)

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“…In this project, we optimized the PMCA protocol for the detection of seeding activity in atypical BSE samples. The complexity of the detection of atypical BSE by PMCA has already been stated in earlier reports of the amplification of l -BSE [46] and H-BSE [47]. After adaptation of our PMCA protocol for the amplification of atypical BSE, we were still able to show a signal amplification using 10 −3 , 10 −6 and 10 −9 dilutions of atypical BSE- (H- and l -BSE) positive brain homogenates, although with a slightly lower repeatability as compared to C-BSE.…”

Section: Discussionmentioning

confidence: 83%

Absence of classical and atypical (H- and L-) BSE infectivity in the blood of bovines in the clinical end stage of disease as confirmed by intraspecies blood transfusion

Balkema‐Buschmann

Ziegler

Priemer

et al. 2021

Journal of General Virology

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While the presence of bovine spongiform encephalopathy (BSE) infectivity in the blood of clinically affected sheep has been proven by intraspecies blood-transfusion experiments, this question has remained open in the case of BSE-affected cattle. Although the absence of infectivity can be anticipated from the restriction of the agent to neuronal tissues in this species, evidence for this was still lacking. This particularly concerns the production and use of medicinal products and other applications containing bovine blood or preparations thereof. We therefore performed a blood-transfusion experiment from cattle in the clinical end stage of disease after experimental challenge with either classical (C-BSE) or atypical (H- and l-) BSE into calves at 4–6 months of age. The animals were kept in a free-ranging group for 10 years. Starting from 24 months post-transfusion, a thorough clinical examination was performed every 6 weeks in order to detect early symptoms of a BSE infection. Throughout the experiment, the clinical picture of all animals gave no indication of a BSE infection. Upon necropsy, the brainstem samples were analysed by BSE rapid test as well as by the highly sensitive Protein Misfolding Cyclic Amplification (PMCA), all with negative results. These results add resilient data to confirm the absence of BSE infectivity in the donor blood collected from C-, H- and l-BSE-affected cattle even in the final clinical phase of the disease. This finding has important implications for the risk assessment of bovine blood and blood products in the production of medicinal products and other preparations.

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Section: Discussionmentioning

confidence: 83%

Absence of classical and atypical (H- and L-) BSE infectivity in the blood of bovines in the clinical end stage of disease as confirmed by intraspecies blood transfusion

Balkema‐Buschmann

Ziegler

Priemer

et al. 2021

Journal of General Virology

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“…Atypical BSE has been linked to the origin of classical BSE because of its conversion into classical BSE following serial passages in wild-type mice (L-type BSE [ 11 ]) and bovine transgenic mice (H-type BSE [ 53 ]). Although we have not tested PMCA products of atypical BSE isolates as part of this study, there is no evidence that PMCA products from atypical BSE convert into classical BSE, at least for H-type BSE using bovine brain as substrate [ 54 ]. In fact, we were unable to propagate H-type BSE using the same methodology (S Canoyra, A Marín-Moreno, JM Torres, unpublished observation).…”

Section: Discussionmentioning

confidence: 99%

Experimental transmission of ovine atypical scrapie to cattle

Konold,

Spiropoulos,

Hills

et al. 2023

Vet Res

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Classical bovine spongiform encephalopathy (BSE) in cattle was caused by the recycling and feeding of meat and bone meal contaminated with a transmissible spongiform encephalopathy (TSE) agent but its origin remains unknown. This study aimed to determine whether atypical scrapie could cause disease in cattle and to compare it with other known TSEs in cattle. Two groups of calves (five and two) were intracerebrally inoculated with atypical scrapie brain homogenate from two sheep with atypical scrapie. Controls were five calves intracerebrally inoculated with saline solution and one non-inoculated animal. Cattle were clinically monitored until clinical end-stage or at least 96 months post-inoculation (mpi). After euthanasia, tissues were collected for TSE diagnosis and potential transgenic mouse bioassay. One animal was culled with BSE-like clinical signs at 48 mpi. The other cattle either developed intercurrent diseases leading to cull or remained clinical unremarkable at study endpoint, including control cattle. None of the animals tested positive for TSEs by Western immunoblot and immunohistochemistry. Bioassay of brain samples from the clinical suspect in Ov-Tg338 and Bov-Tg110 mice was also negative. By contrast, protein misfolding cyclic amplification detected prions in the examined brains from atypical scrapie-challenged cattle, which had a classical BSE-like phenotype. This study demonstrates for the first time that a TSE agent with BSE-like properties can be amplified in cattle inoculated with atypical scrapie brain homogenate.

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“…PMCA is a promising method for prion diagnosis in biological tissues or fluid samples where the concentration of PrP Sc is well below the detection limit of currently available analytical methods. PMCA was able of amplifying extremely low amounts of PrP Sc from the saliva, lymph nodes, palatine tonsils, muscular tissues, and ileocecal regions of BSE-infected cattle [ 141 ] and in urine, cerebrospinal fluid (CSF), and plasma from macaques experimentally infected with classical BSE and atypical L-BSE [ 150 , 151 ]. The presence of PrP Sc in the blood of BSE-affected cattle has not been confirmed, indicating that BSE is not transmitted through the blood [ 141 ].…”

Section: Protein Misfolding Cyclic Amplification (Pmca)mentioning

confidence: 99%

Conventional and State-of-the-Art Detection Methods of Bovine Spongiform Encephalopathy (BSE)

Olech

2023

IJMS

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Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disease that belongs to a group of diseases known as transmissible spongiform encephalopathies (TSEs). It is believed that the infectious agent responsible for prion diseases is abnormally folded prion protein (PrPSc), which derives from a normal cellular protein (PrPC), which is a cell surface glycoprotein predominantly expressed in neurons. There are three different types of BSE, the classical BSE (C-type) strain and two atypical strains (H-type and L-type). BSE is primarily a disease of cattle; however, sheep and goats also can be infected with BSE strains and develop a disease clinically and pathogenically indistinguishable from scrapie. Therefore, TSE cases in cattle and small ruminants require discriminatory testing to determine whether the TSE is BSE or scrapie and to discriminate classical BSE from the atypical H- or L-type strains. Many methods have been developed for the detection of BSE and have been reported in numerous studies. Detection of BSE is mainly based on the identification of characteristic lesions or detection of the PrPSc in the brain, often by use of their partial proteinase K resistance properties. The objective of this paper was to summarize the currently available methods, highlight their diagnostic performance, and emphasize the advantages and drawbacks of the application of individual tests.

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In vitro amplification of H-type atypical bovine spongiform encephalopathy by protein misfolding cyclic amplification

Cited by 4 publications

References 26 publications

Absence of classical and atypical (H- and L-) BSE infectivity in the blood of bovines in the clinical end stage of disease as confirmed by intraspecies blood transfusion

Absence of classical and atypical (H- and L-) BSE infectivity in the blood of bovines in the clinical end stage of disease as confirmed by intraspecies blood transfusion

Experimental transmission of ovine atypical scrapie to cattle

Conventional and State-of-the-Art Detection Methods of Bovine Spongiform Encephalopathy (BSE)

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