Abstract
Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative disorders caused by prions. Animal TSE include scrapie in sheep and goats, and chronic wasting disease (CWD) in cervids. Effective management of scrapie in many parts of the world, and of CWD in North American deer population is complicated by the persistence of prions in the environment. After shedding from diseased animals, prions persist in soil, withstanding biotic and abiotic degradation. As soil is a complex, multi-component system of both mineral and organic components, it is important to understand which soil compounds may interact with prions and thus contribute to disease transmission. Several studies have investigated the role of different soil minerals in prion adsorption and infectivity; we focused our attention on the interaction of soil organic components, the humic substances (HS), with recombinant prion protein (recPrP) material. We evaluated the kinetics of recPrP adsorption, providing a structural and biochemical characterization of chemical adducts using different experimental approaches. Here we show that HS act as potent anti-prion agents in prion infected neuronal cells and in the amyloid seeding assays: HS adsorb both recPrP and prions, thus sequestering them from the prion replication process. We interpreted our findings as highly relevant from an environmental point of view, as the adsorption of prions in HS may affect their availability and consequently hinder the environmental transmission of prion diseases in ruminants.
Highlights
Prions are proteinaceous infectious agents causing a heterogeneous group of invariably fatal neurodegenerative disorders denoted as transmissible spongiform encephalopathies (TSE) or prion diseases
From other protein detection methods [44], circular dichroism (CD) spectroscopy detected no interference in humic substances (HS) (Figure S1)
Our results suggest that FA are more effective in inducing MoPrP precipitation, as 97% and 58% of MoPrP was soluble after 6 hours of incubation with 5 mg/mL HA and FA, respectively
Summary
Prions are proteinaceous infectious agents causing a heterogeneous group of invariably fatal neurodegenerative disorders denoted as transmissible spongiform encephalopathies (TSE) or prion diseases. Creutzfeldt-Jakob disease (CJD) is the most common form of TSE in humans whereas animal TSE include scrapie in sheep and goat, chronic wasting disease (CWD) in cervids and bovine spongiform encephalopathy (BSE) in cattle [1]. Scrapie and CWD can be transmitted via environmental routes, while BSE is transmitted almost exclusively through foodborne carriages [4]. In BSE, PrPSc accumulation has been largely found within the CNS [9] whereas scrapie and CWD have exhibited a widespread prion distribution in different tissues [10,11]. The PrPSc tropism observed in sheep and cervids accounts for the facile TSE transmission among these animals, which may disseminate prions via multiple excretion routes [12]. The interaction of prions with soil OM may be highly environmentally relevant for soils rich in HS, but the mechanism of HS-PrPSc interaction and the influence of HS on prion infectivity are not well understood
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