RT-QuIC detection of pathological prion protein in subclinical goats following experimental oral transmission of L-type BSE (original) (raw)
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Journal of General Virology, 2007
The presence of BSE prion infectivity in asymptomatic cattle and its tissue distribution are important concerns for both human and veterinary health and food safety. In this work, a collection of tissues from asymptomatic cattle challenged orally with BSE and culled at 20, 24, 27, 30 and 33 months have been used to inoculate intracerebrally BoPrP-Tg110 mice expressing bovine PrP to assess their infectivity. Results demonstrate that BSE infectivity in asymptomatic cattle is essentially restricted to the nervous system, Peyer's patches and tonsils, as reported previously for terminally BSE-diseased cattle. BSE infectivity was detectable in Peyer's patches and tonsils at all time points analysed, but infectivity in nervous tissues (brainstem and sciatic nerve) was only detectable after 27 months from inoculation. Infectivity in brainstem increased markedly at 33 months after inoculation. All other investigated tissues or fluids (spleen, skeletal muscle, blood and urine) reveale...
Frontiers in veterinary science, 2017
Bovine spongiform encephalopathy (BSE) belongs to a group of fatal prion diseases that result from the misfolding of the cellular prion protein (PrP) into a pathogenic form (PrP) that accumulates in the brain. assays such as serial protein misfolding amplification and real-time quaking-induced conversion (RT-QuIC) allow assessment of the conversion of PrP to PrP. RT-QuIC can be used for the detection of prions in a variety of biological tissues from humans and animals. However, there is no such comparison of RT-QuIC data between BSE positive and presymptomatic cattle. Further, the current study assesses prion distribution in multiple brain regions of clinically ill or subclinical animals. Here, we compare RT-QuIC reactions seeded with brain samples collected from experimentally inoculated cattle that were clinically ill or subclinically affected with BSE. The results demonstrate RT-QuIC seeding in various brain regions of an animal with subclinical BSE despite being determined negat...
Scientific Reports
Since 2005, two cases of natural bovine spongiform encephalopathies (BSE) have been reported in goats. Furthermore, experimental transmissions of classical (C-BSE) and atypical (L-BSE) forms of BSE in goats were also reported. To minimize further spreading of prion diseases in small ruminants the development of a highly sensitive and specific test for ante-mortem detection of infected animals would be of great value. Recent studies reported high diagnostic value of a second generation of cerebrospinal fluid (CSF) Real-Time Quaking-Induced Conversion (RT-QuIC) assay across a wide spectrum of human prions. Here, we applied this improved QuIC (IQ-CSF) for highly efficient detection of TSEs prion protein in goat cerebrospinal fluid. IQ-CSF sensitivity and specificity were evaluated on CSF samples collected at disease endpoint from goats naturally and experimentally infected with scrapie or bovine isolates of C-Bse and L-Bse, respectively. Next, CsF samples collected from L-Bse infected goats during pre-symptomatic stage were also analysed. PrP L-Bse associated seeding activity was detected at early time points after experimental inoculation, with an average time of 439 days before clinical symptoms appeared. taken together these data are indicative of the great potential of this in vitro prion amplification assay as ante-mortem tse test for live and asymptomatic small ruminants. Transmissible Spongiform Encephalopathies (TSEs) or prion diseases are fatal neurodegenerative diseases that include Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and chronic wasting disease (CWD) in cervids. The infectious agent responsible for these diseases, the prion, appears to be composed primarily of an abnormal, misfolded and oligomeric (PrP Sc) form of the cellular prion protein (PrP C) 1,2. PrP Sc induces the polymerization and conformational conversion of PrP C to its infectious form 3-5 or, in a variety of in vitro conversion assays 6 , into alternative forms of the prion protein which are, similarly to PrP Sc , partially resistant to digestion with proteases (PrP Res). The pathogenic isoform of the prion protein is therefore a marker associated to TSEs which acts as a seed allowing the ultrasensitive detection of PrP Sc using in vitro prion amplification reactions such as Real-Time Quaking Induced Conversion (RT-QuIC) 7. The spread of BSE agent to small ruminants is a major issue in the surveillance of TSEs because BSE passage into a new host may change strain properties, make it difficult to recognize the original strain, and increasing the risk of epidemic spread 8. Since 2005, two natural BSE cases have been reported in goats 9,10. Furthermore,
PloS one, 2017
Prions are amyloid-forming proteins that cause transmissible spongiform encephalopathies through a process involving conversion from the normal cellular prion protein to the pathogenic misfolded conformation (PrPSc). This conversion has been used for in vitro assays including serial protein misfolding amplification and real-time quaking induced conversion (RT-QuIC). RT-QuIC can be used for the detection of prions in a variety of biological tissues from humans and animals. Extensive work has been done to demonstrate that RT-QuIC is a rapid, specific, and highly sensitive prion detection assay. RT-QuIC uses recombinant prion protein to detect minute amounts of PrPSc. RT-QuIC has been successfully used to detect PrPSc from different prion diseases with a variety of substrates including hamster, human, sheep, bank vole, bovine and chimeric forms of prion protein. However, recombinant bovine prion protein has not been used to detect transmissible mink encephalopathy (TME) or to different...
Journal of Virology, 2008
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Veterinary research, 2017
In classical bovine spongiform encephalopathy (C-BSE), an orally acquired prion disease of cattle, the ileal Peyer's patch (IPP) represents the main entry port for the BSE agent. In earlier C-BSE pathogenesis studies, cattle at 4-6 months of age were orally challenged, while there are strong indications that the risk of infection is highest in young animals. In the present study, unweaned calves aged 4-6 weeks were orally challenged to determine the earliest time point at which newly formed PrP BSE and BSE infectivity are detectable in the IPP. For this purpose, calves were culled 1 week as well as 2, 4, 6 and 8 months post-infection (mpi) and IPPs were examined for BSE infectivity using a bovine PrP transgenic mouse bioassay, and for PrP BSE by immunohistochemistry (IHC) and protein misfolding cyclic amplification (PMCA) assays. For the first time, BSE prions were detected in the IPP as early as 2 mpi by transgenic mouse bioassay and PMCA and 4 mpi by IHC in the follicular dendritic cells (FDCs) of the IPP follicles. These data indicate that BSE prions propagate in the IPP of unweaned calves within 2 months of oral uptake of the agent.
Emerging Infectious Diseases, 2011
Bovine spongiform encephalopathy (BSE) and BSErelated disorders have been associated with a single major prion strain. Recently, 2 atypical, presumably sporadic forms of BSE have been associated with 2 distinct prion strains that are characterized mainly by distinct Western blot profi les of abnormal protease-resistant prion protein (PrP res), named high-type (BSE-H) and low-type (BSE-L), that also differed from classical BSE. We characterized 5 atypical BSE-H isolates by analyzing their molecular and neuropathologic properties during transmission in transgenic mice expressing homologous bovine prion protein. Unexpectedly, in several inoculated animals, strain features emerged that were highly similar to those of classical BSE agent. These fi ndings demonstrate the capability of an atypical bovine prion to acquire classical BSE-like properties during propagation in a homologous bovine prion protein context and support the view that the epidemic BSE agent could have originated from such a cattle prion.