Strain variation in treatment and prevention of human prion diseases

Ellett, Laura J; Revill, Zoe T; Koo, Yong Qian; Lawson, Victoria

doi:10.1016/bs.pmbts.2020.08.006

Cited by 7 publications

(5 citation statements)

References 124 publications

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“…This amount is representative of real-life conditions, taking into consideration that the liquid waste we aimed to simulate generally contains only a small fraction of infectious material [32]. Since it is possible that prion strain variation may influence the efficacy of treatment approaches [33], the results of this study apply to RML prion strain in mice and cannot be easily adapted to every prion strain. Yet, in a recent study [34], it was proposed that the efficiency of each inactivation method should be proven for each prion strain against which it is intended to be used.…”

Section: Discussionmentioning

confidence: 99%

A Comparison of RML Prion Inactivation Efficiency by Heterogeneous and Homogeneous Photocatalysis

Paspaltsis,

Kanata,

Sotiriadis

et al. 2024

Pathogens

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Prions are proteinaceous pathogens responsible for a variety of devastating diseases in mammals, including scrapie in sheep and goats, chronic wasting disease in cervids, and Creutzfeldt–Jakob disease (CJD) in humans. They are characterized by their exceptional persistence to common inactivation procedures. This applies to all possible sources of prion contamination as prions may be present in the tissues and biological fluids of infected individuals. Hence, efficient prion inactivation procedures are still being sought to minimize the risk of intra- or inter-species transmission. In the past, photocatalytic treatment has been proven to be capable of efficiently oxidizing and inactivating prions. In the present study, the efficacy of homogeneous photo-Fenton-based photocatalysis as well as heterogeneous photocatalysis with TiO2 in reducing RML mouse scrapie infectivity was evaluated. Prion inactivation was assessed by means of a bioassay, and the results were confirmed by in vitro experiments. While the prion infectivity of the RML mouse scrapie was reduced after treatment with the photo-Fenton reagent, the heterogeneous photocatalytic treatment of the same prion strain completely eliminated prion infectivity.

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Section: Discussionmentioning

confidence: 99%

A Comparison of RML Prion Inactivation Efficiency by Heterogeneous and Homogeneous Photocatalysis

Paspaltsis,

Kanata,

Sotiriadis

et al. 2024

Pathogens

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“…The effectiveness of prion decontaminants can also depend on the prion strain type [ 12 , 25 , 42 , 44 , 48 , 60 , 61 ]. Due to the scarcity of suitable human prion mouse models [ 62 , 63 ], we relied on the rodent-adapted prion strain, RML6, which has been widely used as a model strain for the development and validation of prion decontaminants (Fichet, Comoy et al 2004, Lemmer, Mielke et al 2008, Edgeworth, Sicilia et al 2011, McDonnell, Dehen et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Advancing surgical instrument safety: A screen of oxidative and alkaline prion decontaminants using real-time quaking-induced conversion with prion-coated steel beads as surgical instrument mimetic

Heinzer,

Avar,

Pfammatter

et al. 2024

PLoS ONE

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Iatrogenic transmission of prions, the infectious agents of fatal Creutzfeldt-Jakob disease, through inefficiently decontaminated medical instruments remains a critical issue. Harsh chemical treatments are effective, but not suited for routine reprocessing of reusable surgical instruments in medical cleaning and disinfection processes due to material incompatibilities. The identification of mild detergents with activity against prions is therefore of high interest but laborious due to the low throughput of traditional assays measuring prion infectivity. Here, we report the establishment of TESSA (sTainlESs steel-bead Seed Amplification assay), a modified real-time quaking induced cyclic amplification (RT-QuIC) assay that explores the propagation activity of prions with stainless steel beads. TESSA was applied for the screening of about 70 different commercially available and novel formulations and conditions for their prion inactivation efficacy. One hypochlorite-based formulation, two commercially available alkaline formulations and a manual alkaline pre-cleaner were found to be highly effective in inactivating prions under conditions simulating automated washer-disinfector cleaning processes. The efficacy of these formulations was confirmed in vivo in a murine prion infectivity bioassay, yielding a reduction of the prion titer for bead surface adsorbed prions below detectability. Our data suggest that TESSA represents an effective method for a rapid screening of prion-inactivating detergents, and that alkaline and oxidative formulations are promising in reducing the risk of potential iatrogenic prion transmission through insufficiently decontaminated instrument surfaces.

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“…At the interindividual scale, it defines the prion strain or prion field isolate. The extent of this diversity at least equals the number of prion strains identified thus far [8, 33, 34]. At the strain scale, the structural diversity reflects the coexistence of PrP Sc subpopulations (or substrain conformers) [23, 26].…”

Section: Discussionmentioning

confidence: 99%

“…Such unicity inevitably allows us to conclude that the strain information is not defined by the size of the PrP Sc elementary brick as we previously hypothesized [35] but is defined by the conformation of this dimer. However, considering the growing number of prion strains (considering natural and experimental strains roughly close to 50 [8, 25, 33, 34]), it is not trivial to imagine how such diversity could be encoded in a commune dimeric quaternary structure in a stable manner during multiple replication events without affecting the stability of the oligomerization interface. Such a thermodynamic paradox can be circumvented if the oligomerization domain (i.e., dimerization interface) is structurally independent from the domain encoding the strain information.…”

Section: Discussionmentioning

confidence: 99%

The smallest infectious substructure encoding the prion strain structural determinant revealed by spontaneous dissociation of misfolded prion protein assemblies

Bohl

Moudjou

Herzog

et al. 2023

Preprint

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It is commonly accepted that the prion replicative propensity and strain structural determinant (SSD) are encoded in the fold of PrPSc amyloid fibril assemblies. By exploring the quaternary structure dynamicity of several prion strains, we revealed that all mammalian prion assemblies exhibit the generic property of spontaneously generating two sets of discreet infectious tetrameric and dimeric species differing significantly by their specific infectivity. By using perturbation approaches such as dilution and ionic strength variation, we demonstrated that these two oligomeric species were highly dynamic and evolved differently in the presence of chaotropic agents. In general, our observations of seven different prion strains from three distinct species highlight the high dynamicity of PrPSc assemblies as a common and intrinsic property of mammalian prions. The existence of such small infectious PrPSc species harboring the SSD indicates that the prion infectivity and the SSD are not restricted only to the amyloid fold but can also be encoded in other alternative quaternary structures. Such diversity in the quaternary structure of prion assemblies tends to indicate that the structure of PrPSc can be divided into two independent folding domains: a domain encoding the strain structural determinant and a second domain whose fold determines the type of quaternary structure that could adopt PrPSc assemblies.

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Strain variation in treatment and prevention of human prion diseases

Cited by 7 publications

References 124 publications

A Comparison of RML Prion Inactivation Efficiency by Heterogeneous and Homogeneous Photocatalysis

A Comparison of RML Prion Inactivation Efficiency by Heterogeneous and Homogeneous Photocatalysis

Advancing surgical instrument safety: A screen of oxidative and alkaline prion decontaminants using real-time quaking-induced conversion with prion-coated steel beads as surgical instrument mimetic

The smallest infectious substructure encoding the prion strain structural determinant revealed by spontaneous dissociation of misfolded prion protein assemblies

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