Humic substances interfere with detection of pathogenic prion protein

Smith, Christen B.; Booth, Clarissa J.; Wadzinski, Tyler J.; Legname, Giuseppe; Chappell, Rick; Johnson, Christopher; Pedersen, Joel A.

doi:10.1016/j.soilbio.2013.10.005

Cited by 6 publications

(12 citation statements)

References 47 publications

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“…As shown by mild thermal denaturation, FA inhibit the conversion of recPrP to a PK-resistant PrP Sc -like conformation, which is not available for cell internalization when bound to FA [32]. A recent study has reported that HA-adsorbed PrP Sc strains resulted slightly less infectious when intracerebrally inoculated in hamsters [55]. Nevertheless, further investigations in living organisms are needed to verify this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Prion Protein Interaction with Soil Humic Substances: Environmental Implications

et al. 2014

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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.

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Section: Discussionmentioning

confidence: 99%

Prion Protein Interaction with Soil Humic Substances: Environmental Implications

et al. 2014

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“…There are several potential explanations for the observed decline in PrP CWD signal upon incubation with humic acids. One possibility is that a component of SOM interferes with PrP CWD during immunoblotting which could alter migration, limit entry into the gel, or interfere with membrane transfer [27]. We found that PrP CWD migrated as expected (20–35 kDa) with or without HA, thus altered migration during SDS-PAGE is not the reason for decreasing PrP signal.…”

Section: Resultsmentioning

confidence: 60%

“…Another study [25] has shown HA-like substances copolymerize with recPrP and irreversibly incorporate it into their structure, creating complexes which decrease the efficiency of recPrP recovery. The PrP insolubilization and co-precipitation by aggregation with HA without altering PrP secondary structure, which potentially can decrease prion detectability and reduce their bioavailability, also were discussed [26,27]. Similar prion interactions with another high-organic matrix (e.g.…”

Section: Resultsmentioning

confidence: 99%

“…However, due to difference in structure of infectious and non-infectious prions, they may interact differently with SOM compounds. It has previously been shown that hamster prions, when incubated with low concentrations of HA, remain infectious to hamsters with little biological impact on the incubation period [27]. The objective of this study was to determine, by examining a more complete range of HA concentrations, how interactions with HA affects PrP CWD and resulting infectivity.…”

Section: Introductionmentioning

confidence: 99%

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Soil humic acids degrade CWD prions and reduce infectivity

et al. 2018

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Chronic wasting disease (CWD), an environmentally transmissible, fatal prion disease is endemic in North America, present in South Korea and has recently been confirmed in northern Europe. The expanding geographic range of this contagious disease of free-ranging deer, moose, elk and reindeer has resulted in increasing levels of prion infectivity in the environment. Soils are involved in CWD horizontal transmission, acting as an environmental reservoir, and soil mineral and organic compounds have the ability to bind prions. Upper horizons of soils are usually enriched with soil organic matter (SOM), however, the role of SOM in prion conservation and mobility remains unclear. In this study, we show that incubation of PrPCWD with humic acids (HA), a major SOM compound, affects both the molecular weight and recovery of PrPCWD. Detection of PrPCWD is reduced as HA concentration increases. Native HA extracted from pristine soils also reduces or entirely eliminates PrPCWD signal. Incubation of CWD prions with HA significantly increased incubation periods in tgElk mice demonstrating that HA can reduce CWD infectivity.

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“…Although not confirmed in natural environment, this hypothesis found supports in previous study in animal models showing that prions bound to a soil rich in HS are less infectious than PrP Sc adsorbed to montmorillonite [ 19 ]. Another study has reported that HA-adsorbed PrP Sc strains resulted slightly less infectious when intracerebrally inoculated in hamsters [ 30 ]. However, if HS-bound prions retain infectivity upon oral ingestion in ruminants and in cervids is still debated [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

The mechanisms of humic substances self-assembly with biological molecules: The case study of the prion protein

et al. 2017

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Humic substances (HS) are the largest constituent of soil organic matter and are considered as a key component of the terrestrial ecosystem. HS may facilitate the transport of organic and inorganic molecules, as well as the sorption interactions with environmentally relevant proteins such as prions. Prions enter the environment through shedding from live hosts, facilitating a sustained incidence of animal prion diseases such as Chronic Wasting Disease and scrapie in cervid and ovine populations, respectively. Changes in prion structure upon environmental exposure may be significant as they can affect prion infectivity and disease pathology. Despite its relevance, the mechanisms of prion interaction with HS are still not completely understood. The goal of this work is to advance a structural-level picture of the encapsulation of recombinant, non-infectious, prion protein (PrP) into different natural HS. We observed that PrP precipitation upon addition of HS is mainly driven by a mechanism of “salting-out” whereby PrP molecules are rapidly removed from the solution and aggregate in insoluble adducts with humic molecules. Importantly, this process does not alter the protein folding since insoluble PrP retains its α-helical content when in complex with HS. The observed ability of HS to promote PrP insolubilization without altering its secondary structure may have potential relevance in the context of “prion ecology”. These results suggest that soil organic matter interacts with prions possibly without altering the protein structures. This may facilitate prions preservation from biotic and abiotic degradation leading to their accumulation in the environment.

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Humic substances interfere with detection of pathogenic prion protein

Cited by 6 publications

References 47 publications

Prion Protein Interaction with Soil Humic Substances: Environmental Implications

Prion Protein Interaction with Soil Humic Substances: Environmental Implications

Soil humic acids degrade CWD prions and reduce infectivity

The mechanisms of humic substances self-assembly with biological molecules: The case study of the prion protein

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