RESUMEN
BACKGROUND: Atypical/Nor98 scrapie (AS) is an idiopathic infectious prion disease affecting sheep and goats. Recent findings suggest that zoonotic prions from classical bovine spongiform encephalopathy (C-BSE) may copropagate with atypical/Nor98 prions in AS sheep brains. Investigating the risk AS poses to humans is crucial. METHODS: To assess the risk of sheep/goat-to-human transmission of AS, we serially inoculated brain tissue from field and laboratory isolates into transgenic mice overexpressing human prion protein (Met129 allele). We studied clinical outcomes as well as presence of prions in brains and spleens. RESULTS: No transmission occurred on the primary passage, with no clinical disease or pathological prion protein in brains and spleens. On subsequent passages, 1 isolate gradually adapted, manifesting as prions with a phenotype resembling those causing MM1-type sporadic Creutzfeldt-Jakob disease in humans. However, further characterization using in vivo and in vitro techniques confirmed both prion agents as different strains, revealing a case of phenotypic convergence. Importantly, no C-BSE prions emerged in these mice, especially in the spleen, which is more permissive than the brain for C-BSE cross-species transmission. CONCLUSIONS: The results obtained suggest a low zoonotic potential for AS. Rare adaptation may allow the emergence of prions phenotypically resembling those spontaneously forming in humans.
Asunto(s)
Encéfalo , Síndrome de Creutzfeldt-Jakob , Cabras , Ratones Transgénicos , Priones , Scrapie , Zoonosis , Animales , Síndrome de Creutzfeldt-Jakob/transmisión , Síndrome de Creutzfeldt-Jakob/patología , Síndrome de Creutzfeldt-Jakob/metabolismo , Humanos , Scrapie/transmisión , Scrapie/patología , Ratones , Zoonosis/transmisión , Encéfalo/patología , Encéfalo/metabolismo , Ovinos , Bovinos , Priones/metabolismo , Fenotipo , Bazo/patología , Encefalopatía Espongiforme Bovina/transmisión , Encefalopatía Espongiforme Bovina/patología , Encefalopatía Espongiforme Bovina/metabolismo , Enfermedades de las Cabras/transmisión , Enfermedades de las Cabras/patología , Modelos Animales de EnfermedadRESUMEN
The first case of CWD in a Norwegian red deer was detected by a routine ELISA test and confirmed by western blotting and immunohistochemistry in the brain stem of the animal. Two different western blotting tests were conducted independently in two different laboratories, showing that the red deer glycoprofile was different from the Norwegian CWD reindeer and CWD moose and from North American CWD. The isolate showed nevertheless features similar to the classical BSE (BSE-C) strain. Furthermore, BSE-C could not be excluded based on the PrPSc immunohistochemistry staining in the brainstem and the absence of detectable PrPSc in the lymphoid tissues. Because of the known ability of BSE-C to cross species barriers as well as its zoonotic potential, the CWD red deer isolate was submitted to the EURL Strain Typing Expert Group (STEG) as a BSE-C suspect for further investigation. In addition, different strain typing in vivo and in vitro strategies aiming at identifying the BSE-C strain in the red deer isolate were performed independently in three research groups and BSE-C was not found in it. These results suggest that the Norwegian CWD red deer case was infected with a previously unknown CWD type and further investigation is needed to determine the characteristics of this potential new CWD strain.
Asunto(s)
Ciervos , Encefalopatía Espongiforme Bovina , Enfermedad Debilitante Crónica , Animales , Noruega , Western Blotting/veterinaria , Ensayo de Inmunoadsorción Enzimática/veterinaria , Priones/metabolismo , Bovinos , Inmunohistoquímica/veterinaria , Proteínas PrPSc/metabolismoRESUMEN
Human spongiform encephalopathies are rare transmissible neurodegenerative diseases of the brain and the nervous system that are caused by misfolding of the physiological prion protein into a pathological form and its deposition in the central nervous system (CNS). Prion diseases include Creutzfeldt-Jakob disease (CJD, sporadic or familial), Gerstmann-Straussler-Scheinker syndrome (GSS) and fatal familial insomnia (FFI). Prion diseases can be differentiated into three etiological categories: spontaneous (sporadic CJD), inherited (familial CJD, FFI, and GSS) and acquired (variant CJD and iatrogenic CJD). Most cases occur sporadically. Prion diseases can lead to a variety of neurological symptoms and always have an inevitably fatal course. Cerebrospinal fluid analysis and magnetic resonance imaging (MRI) play a crucial role in the diagnostics of prion diseases and may facilitate an early and reliable clinical diagnosis. A causal treatment or specific therapeutic agents are not yet available. In general, a palliative therapeutic concept is indicated.
Asunto(s)
Síndrome de Creutzfeldt-Jakob , Encefalopatía Espongiforme Bovina , Enfermedad de Gerstmann-Straussler-Scheinker , Enfermedades por Prión , Animales , Bovinos , Humanos , Enfermedades por Prión/diagnóstico , Enfermedades por Prión/patología , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/patología , Enfermedad de Gerstmann-Straussler-Scheinker/diagnóstico , Enfermedad de Gerstmann-Straussler-Scheinker/genética , Enfermedad de Gerstmann-Straussler-Scheinker/patología , Encéfalo/patología , Encefalopatía Espongiforme Bovina/patologíaRESUMEN
Atypical infections of the brain and spine caused by parasites occur in immunocompetent and immunosuppressed hosts, related to exposure and more prevalently in endemic regions. In the United States, the most common parasitic infections that lead to central nervous system manifestations include cysticercosis, echinococcosis, and toxoplasmosis, with toxoplasmosis being the most common opportunistic infection affecting patients with advanced HIV/AIDS. Another rare but devastating transmittable disease is prion disease, which causes rapidly progressive spongiform encephalopathies. Familiarity and understanding of various infectious agents are a crucial aspect of diagnostic neuroradiology, and recognition of unique features can aid timely diagnosis and treatment.
Asunto(s)
Enfermedades Transmisibles , Encefalopatía Espongiforme Bovina , Parásitos , Enfermedades por Prión , Toxoplasmosis , Animales , Bovinos , Humanos , Encefalopatía Espongiforme Bovina/diagnóstico , Imagen por Resonancia Magnética/métodos , Enfermedades por Prión/diagnóstico , Encéfalo/diagnóstico por imagenRESUMEN
Efforts to prevent human-to-human transmission of variant Creutzfeldt-Jakob disease (vCJD) by contaminated blood would be aided by the development of a sensitive diagnostic test that could be routinely used to screen blood donations. As blood samples from vCJD patients are extremely rare, here we describe the optimisation of real-time quaking-induced conversion (RT-QuIC) for detection of PrPSc (misfolded prion protein, a marker of prion infection) in blood samples from an established large animal model of vCJD, sheep experimentally infected with bovine spongiform encephalopathy (BSE). Comparative endpoint titration experiments with RT-QuIC, miniaturized bead protein misfolding cyclic amplification (mb-PMCA) and intracerebral inoculation of a transgenic mouse line expressing sheep PrP (tgOvARQ), demonstrated highly sensitive detection of PrPSc by RT-QuIC in a reference sheep brain homogenate. Upon addition of a capture step with iron oxide beads, the RT-QuIC assay was able to detect PrPSc in whole blood samples from BSE-infected sheep up to two years before disease onset. Both RT-QuIC and mb-PMCA also demonstrated sensitive detection of PrPSc in a reference vCJD-infected human brain homogenate, suggesting that either assay may be suitable for application to human blood samples. Our results support the further development and evaluation of RT-QuIC as a diagnostic or screening test for vCJD.
Asunto(s)
Síndrome de Creutzfeldt-Jakob , Encefalopatía Espongiforme Bovina , Priones , Bovinos , Ratones , Humanos , Animales , Ovinos , Priones/metabolismo , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/metabolismo , Encéfalo/metabolismo , Proteínas Priónicas/metabolismo , Encefalopatía Espongiforme Bovina/diagnóstico , Encefalopatía Espongiforme Bovina/metabolismoRESUMEN
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.
Asunto(s)
Enfermedades de los Bovinos , Encefalopatía Espongiforme Bovina , Priones , Scrapie , Enfermedades de las Ovejas , Ovinos , Animales , Bovinos , Ratones , Scrapie/metabolismo , Priones/genética , Encefalopatía Espongiforme Bovina/metabolismo , Encéfalo/metabolismo , Ratones Transgénicos , Enfermedades de los Bovinos/metabolismo , Enfermedades de las Ovejas/diagnósticoRESUMEN
Numerous studies have investigated the cellular prion protein (PrPC) since its discovery. These investigations have explained that its structure is predominantly composed of alpha helices and short beta sheet segments, and when its abnormal scrapie isoform (PrPSc) is infected, PrPSc transforms the PrPC, leading to prion diseases, including Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in cattle. Given its ubiquitous distribution across a variety of cellular types, the PrPC manifests a diverse range of biological functions, including cell-cell adhesion, neuroprotection, signalings, and oxidative stress response. PrPC is also expressed in immune tissues, and its functions in these tissues include the activation of immune cells and the formation of secondary lymphoid tissues, such as the spleen and lymph nodes. Moreover, high expression of PrPC in immune cells plays a crucial role in the pathogenesis of prion diseases. In addition, it affects inflammation and the development and progression of cancer via various mechanisms. In this review, we discuss the studies on the role of PrPC from various immunological perspectives. [BMB Reports 2023; 56(12): 645-650].
Asunto(s)
Encefalopatía Espongiforme Bovina , Enfermedades por Prión , Priones , Humanos , Animales , Bovinos , Proteínas Priónicas/química , Proteínas Priónicas/metabolismo , Enfermedades por Prión/patología , Enfermedades por Prión/prevención & control , Encefalopatía Espongiforme Bovina/metabolismo , Encefalopatía Espongiforme Bovina/prevención & control , Sistema Inmunológico/metabolismoRESUMEN
The emergence of bovine spongiform encephalopathy (BSE) prions from atypical scrapie has been recently observed upon experimental transmission to rodent and swine models. This study aimed to assess whether the inoculation of atypical scrapie could induce BSE-like disease in cattle. Four calves were intracerebrally challenged with atypical scrapie. Animals were euthanized without clinical signs of prion disease and tested negative for PrPSc accumulation by immunohistochemistry and western blotting. However, an emergence of BSE-like prion seeding activity was detected during in vitro propagation of brain samples from the inoculated animals. These findings suggest that atypical scrapie may represent a potential source of BSE infection in cattle.
Asunto(s)
Enfermedades de los Bovinos , Encefalopatía Espongiforme Bovina , Enfermedades por Prión , Priones , Scrapie , Enfermedades de las Ovejas , Enfermedades de los Porcinos , Ovinos , Femenino , Bovinos , Animales , Porcinos , Enfermedades por Prión/veterinaria , Encéfalo/metabolismoRESUMEN
Three retrospective lymphoreticular tissue studies (Appendix I, II, and III) aimed to estimate the UK prevalence of variant Creutzfeldt-Jakob disease (vCJD), following exposure of the population to the bovine spongiform encephalopathy (BSE) agent, in the late 1980s and 1990s. These studies evaluated the presence of abnormal prion protein aggregates, in archived formalin-fixed paraffin-embedded (FFPE) appendectomy samples, by immunohistochemical detection. Although there was concordance in the estimated prevalence of vCJD from these studies, the identification of positive specimens from pre- and post-BSE-exposure periods in Appendix III study has raised questions regarding the nature and origin of the detected abnormal prion protein. We applied a robust and novel approach in the extraction of disease-associated prion protein (PrPSc) present in frozen and FFPE samples of brain and appendix from a patient with pathologically confirmed vCJD. The extracted material was used to seed the highly sensitive protein misfolding cyclic amplification assay (hsPMCA) to investigate the in vitro and in vivo propagation properties of the extracted abnormal prion protein. We demonstrate that PrPSc can be successfully extracted from FFPE appendix tissue and propagated in vitro. Bioassay in wild-type and gene-targeted mouse models confirmed that the extracted and amplified product is infectious and retains strain properties consistent with vCJD. This provides a highly sensitive and reliable platform for subsequent analysis of the archived FFPE appendix tissue derived from the Appendix II and III surveys, to further evaluate the nature of the abnormal PrP detected in the positive samples.
Asunto(s)
Síndrome de Creutzfeldt-Jakob , Encefalopatía Espongiforme Bovina , Enfermedades por Prión , Priones , Ratones , Animales , Bovinos , Humanos , Síndrome de Creutzfeldt-Jakob/metabolismo , Proteínas Priónicas/metabolismo , Estudios Retrospectivos , Encéfalo/metabolismo , Priones/metabolismo , Enfermedades por Prión/metabolismo , Encefalopatía Espongiforme Bovina/metabolismoAsunto(s)
Síndrome de Creutzfeldt-Jakob , Encefalopatía Espongiforme Bovina , Animales , Femenino , Humanos , Bovinos , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/epidemiología , Encefalopatía Espongiforme Bovina/diagnóstico , Encefalopatía Espongiforme Bovina/epidemiología , Brotes de EnfermedadesRESUMEN
Abnormal prion proteins (PrPSc) are the disease-associated isoform of cellular prion protein and diagnostic markers of transmissible spongiform encephalopathies (TSEs). These neurodegenerative diseases affect humans and several animal species and include scrapie, zoonotic bovine spongiform encephalopathy (BSE), chronic wasting disease of cervids (CWD), and the newly identified camel prion disease (CPD). Diagnosis of TSEs relies on immunodetection of PrPSc by application of both immunohistochemistry (IHC) and western immunoblot methods (WB) on encephalon tissues, namely, the brainstem (obex level). IHC is a widely used method that uses primary antibodies (monoclonal or polyclonal) against antigens of interest in cells of a tissue section. The antibody-antigen binding can be visualized by a color reaction that remains localized in the area of the tissue or cell where the antibody was targeted. As such, in prion diseases, as in other fields of research, the immunohistochemistry techniques are not solely used for diagnostic purposes but also in pathogenesis studies. Such studies involve detecting the PrPSc patterns and types from those previously described to identify the new prion strains. As BSE can infect humans, it is recommended that biosafety laboratory level-3 (BSL-3) facilities and/or practices are used to handle cattle, small ruminants, and cervid samples included in the TSE surveillance. Additionally, containment and prion-dedicated equipment are recommended, whenever possible, to limit contamination. The PrPSc IHC procedure consists of a formic acid epitope-demasking step also acting as a prion inactivation measure, as formalin-fixed and paraffin-embedded tissues used in this technique remain infectious. When interpreting the results, care must be taken to distinguish non-specific immunolabeling from target labeling. For this purpose, it is important to recognize artifacts of immunolabeling obtained in known TSE-negative control animals to differentiate those from specific PrPSc immunolabeling types, which can vary between TSE strains, host species, and prnp genotype, further described herein.
Asunto(s)
Ciervos , Encefalopatía Espongiforme Bovina , Enfermedades por Prión , Priones , Scrapie , Enfermedad Debilitante Crónica , Animales , Ovinos , Bovinos , Humanos , Proteínas Priónicas , Inmunohistoquímica , Enfermedades por Prión/diagnóstico , Enfermedades por Prión/metabolismo , Scrapie/diagnóstico , Priones/metabolismo , Encefalopatía Espongiforme Bovina/diagnóstico , Encefalopatía Espongiforme Bovina/patología , Enfermedad Debilitante Crónica/diagnósticoRESUMEN
Strict bans on specific risk materials (SRMs) are in place to prevent the spread of bovine spongiform encephalopathy (BSE). SRMs are characterized as tissues in cattle where misfolded proteins, the potential source of BSE infection, are concentrated. As a result of these bans, SRMs must be strictly isolated and disposed of, resulting in great costs for rendering companies. The increasing yield and the landfill of SRMs also exacerbated the burden on the environment. To cope with the emergence of SRMs, novel disposal methods and feasible value-added conversion routes are needed. The focus of this review is on the valorization progress achieved in the conversion of peptides derived from SRMs via an alternative disposal method, thermal hydrolysis. Promising value-added conversion of SRM-derived peptides into tackifiers, wood adhesives, flocculants, and bioplastics, is introduced. The potential conjugation strategies that can be adapted to SRM-derived peptides for desired properties are also critically reviewed. The purpose of this review is to discover a technical platform through which other hazardous proteinaceous waste, SRMs, can be treated as a high-demand feedstock for the production of renewable materials.
Asunto(s)
Encefalopatía Espongiforme Bovina , Animales , Bovinos , Encefalopatía Espongiforme Bovina/prevención & control , ProteínasRESUMEN
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.
Asunto(s)
Encefalopatía Espongiforme Bovina , Enfermedades Neurodegenerativas , Enfermedades por Prión , Priones , Scrapie , Ovinos , Bovinos , Animales , Scrapie/metabolismo , Encefalopatía Espongiforme Bovina/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Enfermedades por Prión/metabolismo , Priones/metabolismo , Rumiantes/metabolismo , Encéfalo/metabolismo , Cabras/metabolismoRESUMEN
Prion diseases are fatal infectious neurodegenerative disorders and prototypic conformational diseases, caused by the conformational conversion of the normal cellular prion protein (PrPC) into the pathological PrPSc isoform. Examples are scrapie in sheep and goat, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in cervids, and Creutzfeldt-Jacob disease (CJD) in humans. There are no therapies available, and animal prion diseases like BSE and CWD can negatively affect the economy, ecology, animal health, and possibly human health. BSE is a confirmed threat to human health, and mounting evidence supports the zoonotic potential of CWD. CWD is continuously expanding in North America in numbers and distribution and was recently identified in Scandinavian countries. CWD is the only prion disease occurring both in wild and farmed animals, which, together with extensive shedding of infectivity into the environment, impedes containment strategies. There is currently a strong push to develop vaccines against CWD, including ones that can be used in wildlife. The immune system does not develop a bona fide immune response against prion infection, as PrPC and PrPSc share an identical protein primary structure, and prions seem not to represent a trigger for immune responses. This asks for alternative vaccine strategies, which focus on PrPC-directed self-antibodies or exposure of disease-specific structures and epitopes. Several groups have established a proof-of-concept that such vaccine candidates can induce some levels of protective immunity in cervid and rodent models without inducing unwanted side effects. This review will highlight the most recent developments and discuss progress and challenges remaining.
Asunto(s)
Ciervos , Encefalopatía Espongiforme Bovina , Enfermedades por Prión , Priones , Vacunas , Enfermedad Debilitante Crónica , Animales , Bovinos , Humanos , Ovinos , Objetivos , Enfermedades por Prión/prevención & control , Enfermedades por Prión/metabolismo , Priones/metabolismo , Encefalopatía Espongiforme Bovina/metabolismo , Enfermedad Debilitante Crónica/prevención & control , Enfermedad Debilitante Crónica/metabolismo , Ciervos/metabolismo , CabrasRESUMEN
Susceptibility to classical bovine spongiform encephalopathy (BSE) has been linked to 23 bp indel in promoter and 12 bp indel in the first intron of cattle prion protein gene. This study aimed to investigate 23/12 bp indel polymorphisms in the polymorphisms in cattle prion protein (PRNP) gene to reveal the risk of BSE in Ethiopian cattle. Also, frequency of each polymorphism was compared to the other Bos taurus and Bos indicus breeds. According to results, the insertion variant was detected at a low frequency in all of the study populations at both loci. The 23 bp insertion allele in Fogera breed was relatively lower than Borona and Arsi and the same allele at the same locus in Afar breed was higher than the rest of the breeds (0.16). Due to high linkage disequilibrium (LD) of the deletion allele in Bos taurus, the frequencies of deletion allele at 23 bp (0.84) and 12 bp (0.86) loci in Afar breed were relatively closer than the rest of the breeds. In addition, DD/DD was found as the highly frequent diplotype in all of the breeds. The low frequency of insertion alleles at 23 and 12 bp indel sites demonstrate that Ethiopian cattle have a genetically high risk for BSE.
Asunto(s)
Enfermedades de los Bovinos , Encefalopatía Espongiforme Bovina , Priones , Bovinos/genética , Animales , Proteínas Priónicas/genética , Priones/genética , Encefalopatía Espongiforme Bovina/epidemiología , Encefalopatía Espongiforme Bovina/genética , Polimorfismo Genético/genética , Regiones Promotoras Genéticas , Frecuencia de los Genes , Enfermedades de los Bovinos/genéticaRESUMEN
Real-time quaking-induced conversion (RT-QuIC) is a cell-free abnormal form of prion protein (PrPSc) amplification method using recombinant prion protein from Escherichia coli that can measure prion seeding activity in samples with high sensitivity. The advantages of this method are that it is much more sensitive than Western blotting, which is usually used to detect PrPSc, and that prion seeding activity can be easily quantified by combining it with endpoint dilution of the sample, and that it can be amplified in most species and prion strains. A decade has passed since the development of RT-QuIC, and many studies have been reported that take advantage of its characteristics. In particular, its usefulness in the diagnosis of sporadic CJD has been clarified, and it is recommended to be one of the diagnostic criteria. Future challenges include the establishment of a method to differentiate prion strains and application of RT-QuIC to early diagnosis of prion diseases and determination of treatment efficacy.
Asunto(s)
Síndrome de Creutzfeldt-Jakob , Encefalopatía Espongiforme Bovina , Enfermedades por Prión , Priones , Animales , Bovinos , Proteínas Priónicas , Western Blotting , Proteínas Recombinantes , Enfermedades por Prión/diagnósticoRESUMEN
Among the numerous transmissible spongiform encephalopathies (TSEs), bovine spongiform encephalopathy (BSE) is the most well-known TSEs. It is a potential Creutzfeldt-Jakob (CJD) disease mutation that can be transferred through cattle to humans. In several animals, the prion protein gene (PRNP) is recognized to take active part in TSE vulnerability or tolerance. Previous studies have found indels polymorphism in PRNP gene promoter and intron1 region linked to BSE vulnerability. It's linked with 23 bp indels polymorphism in putative promoter and 12 bp indel in intron 1 of the PRNP gene. The aim of this study was to compare the allele, genotype and haplotype frequencies of PRNP indel polymorphisms in Zhongdian Yak (Bos grunniens) (YK), Zhongdian Yellow cattle (Bos taurus) (YC) and Zhongdian Yakow (Bos primigenius taurus × Bos grunniens) (PK) with worldwide reported healthy or affected BSE cattle, in order to assess their potential resistance to BSE. A comparison of Chinese bovine populations with healthy and BSE-affected German and Swiss cattle from globally was conducted, and result indicating significant difference (p < .001) between healthy and affected cattle. Additionally, as compared to prior studies with Chinese bovine population, the significant results were found. In this study, the allelic frequency D23 finding high deletion in all analyzed Chinese bovine species, and haplotype D12-D23 exhibited a less significant inclination toward susceptibility to BSE.
Asunto(s)
Enfermedades de los Bovinos , Encefalopatía Espongiforme Bovina , Priones , Animales , Bovinos/genética , Encefalopatía Espongiforme Bovina/genética , Frecuencia de los Genes/genética , Polimorfismo Genético/genética , Proteínas Priónicas/genética , Priones/genéticaRESUMEN
To reduce the transmission risk of bovine spongiform encephalopathy prions (PrPBSE), specified risk materials (SRM) that can harbour PrPBSE are prevented from entering the feed and food chains. As composting is one approach to disposing of SRM, we investigated the inactivation of PrPBSE in lab-scale composters over 28 days and in bin composters over 106-120 days. Lab-scale composting was conducted using 45 kg of feedlot manure with and without chicken feathers. Based on protein misfolding cyclic amplification (PMCA), after 28 days of composting, PrPBSE seeding activity was reduced by 3-4 log10 with feathers and 3 log10 without. Bin composters were constructed using ~ 2200 kg feedlot manure and repeated in 2017 and 2018. PMCA results showed that seeding activity of PrPBSE was reduced by 1-2 log10 in the centre, but only by 1 log10 in the bottom of bin composters. Subsequent assessment by transgenic (Tgbov XV) mouse bioassay confirmed a similar reduction in PrPBSE infectivity. Enrichment for proteolytic microorganisms through the addition of feathers to compost could enhance PrPBSE degradation. In addition to temperature, other factors including varying concentrations of PrPBSE and the nature of proteolytic microbial populations may be responsible for differential degradation of PrPBSE during composting.
Asunto(s)
Compostaje , Encefalopatía Espongiforme Bovina , Priones , Ratones , Animales , Bovinos , Priones/metabolismo , Encefalopatía Espongiforme Bovina/metabolismo , Estiércol , Animales Modificados Genéticamente , Ratones Transgénicos , Encéfalo/metabolismoRESUMEN
The role of the glycosylation status of PrPC in the conversion to its pathological counterpart and on cross-species transmission of prion strains has been widely discussed. Here, we assessed the effect on strain characteristics of bovine spongiform encephalopathy (BSE) isolates with different transmission histories upon propagation on a model expressing a non-glycosylated human PrPC. Bovine, ovine and porcine-passaged BSE, and variant Creutzfeldt-Jakob disease (vCJD) isolates were used as seeds/inocula in both in vitro and in vivo propagation assays using the non-glycosylated human PrPC-expressing mouse model (TgNN6h). After protein misfolding cyclic amplification (PMCA), all isolates maintained the biochemical characteristics of BSE. On bioassay, all PMCA-propagated BSE prions were readily transmitted to TgNN6h mice, in agreement with our previous in vitro results. TgNN6h mice reproduced the characteristic neuropathological and biochemical hallmarks of BSE, suggesting that the absence of glycans did not alter the pathobiological features of BSE prions. Moreover, back-passage of TgNN6h-adapted BSE prions to BoTg110 mice recovered the full BSE phenotype, confirming that the glycosylation of human PrPC is not essential for the preservation of the human transmission barrier for BSE prions or for the maintenance of BSE strain properties.