Mineral licks as environmental reservoirs of chronic wasting disease prions.
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ABSTRACT:
SUBMITTER: Plummer IH
PROVIDER: S-EPMC5931637 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Chronic wasting disease (CWD) is a contagious, fatal prion disease of deer and elk that continues to emerge in new locations. To explore the means by which prions are transmitted with high efficiency among cervids, we examined prion infectivity in the apical skin layer covering the growing antler (antler velvet) by using CWD-susceptible transgenic mice and protein misfolding cyclic amplification. Our finding of prions in antler velvet of CWD-affected elk suggests that this tissue may play a role in disease transmission among cervids. Humans who consume antler velvet as a nutritional supplement are at risk for exposure to prions. The fact that CWD prion incubation times in transgenic mice expressing elk prion protein are consistently more rapid raises the possibility that residue 226, the sole primary structural difference between deer and elk prion protein, may be a major determinant of CWD pathogenesis.
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Project description:Chronic wasting disease (CWD) is a fatal neurodegenerative disease caused by infectious prions (PrPCWD) affecting cervids. Circulating PrPCWD in blood may pose a risk for indirect transmission by way of hematophagous ectoparasites acting as mechanical vectors. Cervids can carry high tick infestations and exhibit allogrooming, a common tick defense strategy between conspecifics. Ingestion of ticks during allogrooming may expose naïve animals to CWD, if ticks harbor PrPCWD. This study investigates whether ticks can harbor transmission-relevant quantities of PrPCWD by combining experimental tick feeding trials and evaluation of ticks from free-ranging white-tailed deer (Odocoileus virginianus). Using the real-time quaking-induced conversion (RT-QuIC) assay, we show that black-legged ticks (Ixodes scapularis) fed PrPCWD-spiked blood using artificial membranes ingest and excrete PrPCWD. Combining results of RT-QuIC and protein misfolding cyclic amplification, we detected seeding activity from 6 of 15 (40%) pooled tick samples collected from wild CWD-infected white-tailed deer. Seeding activities in ticks were analogous to 10-1000 ng of CWD-positive retropharyngeal lymph node collected from deer upon which they were feeding. Estimates revealed a median infectious dose range of 0.3-42.4 per tick, suggesting that ticks can take up transmission-relevant amounts of PrPCWD and may pose a CWD risk to cervids.
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Project description:Cell-based measurement of prion infectivity is currently restricted to experimental strains of mouse-adapted scrapie. Having isolated cell cultures with susceptibility to prions from diseased elk, we describe a modification of the scrapie cell assay allowing evaluation of prions causing chronic wasting disease, a naturally occurring transmissible spongiform encephalopathy. We compare this cervid prion cell assay to bioassays in transgenic mice, the only other existing method for quantification, and show this assay to be a relatively economical and expedient alternative that will likely facilitate studies of this important prion disease.
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Project description:Chronic wasting disease (CWD) is a geographically expanding, fatal neurodegenerative disease in cervids. The disease can be transmitted directly (animal-animal) or indirectly via infectious prions shed into the environment. The precise mechanisms of indirect CWD transmission are unclear but known sources of the infectious prions that contaminate the environment include saliva, urine and feces. We have previously identified PrPC expression in deer interdigital glands, sac-like exocrine structures located between the digits of the hooves. In this study, we assayed for CWD prions within the interdigital glands of CWD infected deer to determine if they could serve as a source of prion shedding and potentially contribute to CWD transmission. Immunohistochemical analysis of interdigital glands from a CWD-infected female mule deer identified disease-associated PrPCWD within clusters of infiltrating leukocytes adjacent to sudoriferous and sebaceous glands, and within the acrosyringeal epidermis of a sudoriferous gland tubule. Proteinase K-resistant PrPCWD material was amplified by serial protein misfolding cyclic amplification (sPMCA) from soil retrieved from between the hoof digits of a clinically affected mule deer. Blinded testing of interdigital glands from 11 mule deer by real-time quake-induced conversion (RT-QuIC) accurately identified CWD-infected animals. The data described suggests that interdigital glands may play a role in the dissemination of CWD prions into the environment, warranting future investigation.
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Project description:Chronic wasting disease (CWD) and sheep scrapie can be transmitted via indirect environmental routes, and it is known that soil can serve as a reservoir of prion infectivity. Given the strong interaction between the prion protein (PrP) and soil, we hypothesized that binding to soil enhances prion resistance to enzymatic digestion, thereby facilitating prion longevity in the environment and providing protection from host degradation. We characterized the performance of a commercially available subtilisin enzyme, Prionzyme, to degrade soil-bound and unbound CWD and HY TME PrP as a function of pH, temperature, and treatment time. The subtilisin enzyme effectively degraded PrP adsorbed to a wide range of soils and soil minerals below the limits of detection. Signal loss occurred rapidly at high pH (12.5) and within 7 days under conditions representative of the natural environment (pH 7.4, 22 degrees C). We observed no apparent difference in enzyme effectiveness between bound and unbound CWD PrP. Our results show that although adsorbed prions do retain relative resistance to enzymatic digestion compared with other brain homogenate proteins, they can be effectively degraded when bound to soil. Our results also suggest a topical application of a subtilisin enzyme solution may be an effective decontamination method to limit disease transmission via environmental "hot spots" of prion infectivity.
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Project description:Prions, the causative agent of chronic wasting disease (CWD) enter the environment through shedding of bodily fluids and carcass decay, posing a disease risk as a result of their environmental persistence. Plants have the ability to take up large organic particles, including whole proteins, and microbes. This study used wheat (Triticum aestivum L.) to investigate the uptake of infectious CWD prions into roots and their transport into aerial tissues. The roots of intact wheat plants were exposed to infectious prions (PrP(TSE)) for 24 h in three replicate studies with PrP(TSE) in protein extracts being detected by western blot, IDEXX and Bio-Rad diagnostic tests. Recombinant prion protein (PrP(C)) bound to roots, but was not detected in the stem or leaves. Protease-digested CWD prions (PrP(TSE)) in elk brain homogenate interacted with root tissue, but were not detected in the stem. This suggests wheat was unable to transport sufficient PrP(TSE) from the roots to the stem to be detectable by the methods employed. Undigested PrP(TSE) did not associate with roots. The present study suggests that if prions are transported from the roots to the stems it is at levels that are below those that are detectable by western blot, IDEXX or Bio-Rad diagnostic kits.
| S-EPMC7030912 | biostudies-literature
Project description:Prions cause fatal infectious neurodegenerative diseases in humans and animals. Cell culture models are essential for studying the molecular biology of prion propagation. Defining such culture models is mostly a random process, includes extensive subcloning, and for many prion diseases few or no models exist. One example is chronic wasting disease (CWD), a highly contagious prion disease of cervids. To extend the range of cell models propagating CWD prions, we gene-edited mouse cell lines known to efficiently propagate murine prions. Endogenous prion protein (PrP) was ablated in CAD5 and MEF cells, using CRISPR-Cas9 editing. PrP knock-out cells were reconstituted with mouse, bank vole and cervid PrP genes by lentiviral transduction. Reconstituted cells expressing mouse PrP provided proof-of-concept for re-established prion infection. Bank voles are considered universal receptors for prions from a variety of species. Bank vole PrP reconstituted cells propagated mouse prions and cervid prions, even without subcloning for highly susceptible cells. Cells reconstituted with cervid PrP and infected with CWD prions tested positive in prion conversion assay, whereas non-reconstituted cells were negative. This novel cell culture platform which is easily adjustable and allows testing of polymorphic alleles will provide important new insights into the biology of CWD prions.
| S-EPMC6673760 | biostudies-literature
Project description:Chronic wasting disease (CWD) has been identified in 30 states in the United States, four provinces in Canada, and recently emerged in Scandinavia. The association of CWD prions with environmental materials such as soil, plants, and surfaces may enhance the persistence of CWD prion infectivity in the environment exacerbating disease transmission. Identifying and quantifying CWD prions in the environment is significant for prion monitoring and disease transmission control. A systematic method for CWD prion quantification from associated environmental materials, however, does not exist. In this study, we developed an innovative method for extracting prions from swabs and recovering CWD prions swabbed from different types of surfaces including glass, stainless steel, and wood. We found that samples dried on swabs were unfavorable for prion extraction, with the greatest prion recovery from wet swabs. Using this swabbing technique, the recovery of CWD prions dried to glass or stainless steel was approximately 30% in most cases, whereas that from wood was undetectable by conventional prion immunodetection techniques. Real-time quake-induced conversion (RT-QuIC) analysis of these same samples resulted in an increase of the detection limit of CWD prions from stainless steel by 4 orders of magnitude. More importantly, the RT-QuIC detection of CWD prions recovered from stainless steel surfaces using this method was similar to the original CWD prion load applied to the surface. This combined surface swabbing and RT-QuIC detection method provides an ultrasensitive means for prion detection across many settings and applications.
| S-EPMC9749837 | biostudies-literature
Project description:Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) that causes a fatal neurodegenerative disease in cervids. Cases of CWD are rapidly increasing in North America among wild and farmed cervid populations, and potential for zoonotic transmission is not yet determined. Therefore, in order to manage the disease, it is imperative to devise a system that can detect CWD during its early phases to prevent spread to new captive herds through introduction of CWD-affected animals into otherwise CWD-free herds. Real-time quaking-induced conversion (RT-QuIC) assays have been applied to detect the presence of disease-associated prions from various samples in both animals and humans. In this study, we have tested the use of five Hofmeister anions that range from weakly hydrating to strongly hydrating: Na3citrate, Na2SO4, NaCl, NaI, and NaClO4 in RT-QuIC reactions for CWD seeding activity using different recombinant prion proteins as substrates. This work shows how the ionic environment of the RT-QuIC reaction can enhance or diminish the seeding activity. The use of Na2SO4 or NaI as the sodium salt for RT-QuIC using bank vole recombinant prion substrate for the detection of CWD using brain samples reduces the lag time to detect with reasonable specificity. For detection of the CWD in fecal samples, only NaI showed comparable reduction in lag time relative to NaCl but required reduced temperature to alleviate spontaneous fibril formation in negative control samples. Selection of the proper ion environment and recombinant prion protein substrate will make RT-QuIC a powerful diagnostic tool for early detection of CWD prions, further supporting CWD surveillance in wild and captive cervids.
| S-EPMC8515057 | biostudies-literature
Project description:Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy negatively impacting cervids on three continents. Soil can serve as a reservoir for horizontal transmission of CWD by interaction with the infectious prion protein (PrPCWD) shed by diseased individuals and from infected carcasses. We investigated the pathways for PrPCWD migration in soil profiles using lab-scale soil columns, comparing PrPCWD migration through pure soil minerals (quartz, illite and montmorillonite), and diverse soils from boreal (Luvisol, Brunisol) and prairie (Chernozem) regions. We analyzed the leachate of the soil columns by immunoblot and protein misfolding cyclic amplification (PMCA) and detected PrP in the leachates of columns composed of quartz, illite, Luvisol and Brunisol. Animal bioassay confirmed the presence of CWD infectivity in the leachates from quartz, illite and Luvisol columns. Leachates from columns with montmorillonite and prairie Chernozems did not contain PrP detectable by immunoblotting or PMCA; bioassay confirmed that the Chernozemic leachate was not infectious. Analysis of the solid phase of the columns confirmed the migration of PrP to lower layers in the illite column, while the strongest signal in the montmorillonite column remained close to the surface. Montmorillonite, the prevalent clay mineral in prairie soils, has the strongest prion binding ability; by contrast, illite, the main clay mineral in northern boreal and tundra soils, does not bind prions significantly. This suggests that in soils of North American CWD-endemic regions (Chernozems), PrPCWD would remain on the soil surface due to avid binding to montmorillonite. In boreal Luvisols and mountain Brunisols, prions that pass through the leaf litter will continue to move through the soil mineral horizon, becoming less bioavailable. In light-textured soils where quartz is a dominant mineral, the majority of the infectious prions will move through the soil profile. Local soil properties may consequently determine the efficiency of environmental transmission of CWD.
| S-EPMC9965917 | biostudies-literature