scholarly journals Complementation between pathological prion protein subassemblies to cross existing species barriers

2019 ◽  
Author(s):  
Angélique Igel-Egalon ◽  
Florent Laferrière ◽  
Philippe Tixador ◽  
Mohammed Moudjou ◽  
Laetitia Herzog ◽  
...  
Keyword(s):  
Prion Protein ◽  
Species Concept ◽  
Structural Heterogeneity ◽  
Size Fractionation ◽  
Species Barrier ◽  
Size Dependent ◽  
Prion Strains ◽  
Insight Into ◽  
Relative Capacity ◽  
Transmission Barrier

AbstractBackgroundprion replication results from the autocatalytic templated assisted conversion of the host-encoded prion protein PrPC into misfolded, polydisperse PrPSc conformers. Structurally distinct PrPSc conformers can give rise to multiple prion strains. Within and between prion strains, the biological activity (replicative efficacy and specific infectivity) of PrPSc assemblies is size-dependent and thus reflects an intrinsic structural heterogeneity. The contribution of such PrPSc heterogeneity across species prion adaptation, - which is believed to be based on fit-adjustment between PrPSc template(s) and host PrPC -, has not been explored.Methodsto define the structural-to-fitness PrPSc landscape, we measured the relative capacity of size-fractionated PrPSc assemblies from different prion strains to cross mounting species barriers in transgenic mice expressing foreign PrPc.Resultsin the absence of a transmission barrier, the relative efficacy of the isolated PrPSc assemblies to induce the disease is superimposable to the efficacy observed in the homotypic context. However, in the presence of a transmission barrier, size fractionation overtly delays and even abrogates prion pathogenesis in both neural and extraneural, prion-permissive tissues, for reason independent of the infectivity load of the isolated assemblies. This suggests that a synergy between structurally distinct PrPSc assemblies in the inoculum is requested for crossing the species barrier. We further strengthen this hypothesis by showing that altering, by serial dilution, PrPSc assemblies content of unfractionated inocula reduce their specific infectivity in an aberrant manner, solely in the presence of a transmission barrier.Conclusionsour data support a mechanism whereby overcoming prion species barrier requires complementation between structurally distinct PrPSc assemblies. This work provides key insight into the “quasi-species” concept applied to prions, which would not necessarily rely on prion sub-strains as constituent but on structural PrPSc heterogeneity within prion population.

scholarly journals Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice

2020 ◽  
Vol 26 (6) ◽  
pp. 1130-1139 ◽  
Author(s):  
Alba Marín-Moreno ◽  
Alvina Huor ◽  
Juan Carlos Espinosa ◽  
Jean Yves Douet ◽  
Patricia Aguilar-Calvo ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Radical Change ◽  
Species Barrier ◽  
Prion Strains

The Unfolding of the Prion Protein Sheds Light on the Mechanisms of Prion Susceptibility and Species Barrier

Biochemistry ◽  
2009 ◽  
Vol 48 (36) ◽  
pp. 8551-8558 ◽  
Author(s):  
Philip J. Robinson ◽  
Teresa J. T. Pinheiro
Keyword(s):  
Prion Protein ◽  
Species Barrier

Rapid size-dependent separation of CdTe quantum dots with prion protein

RSC Advances ◽  
2016 ◽  
Vol 6 (42) ◽  
pp. 35617-35620 ◽  
Author(s):  
Lingyan Zhang ◽  
Yijuan Long ◽  
Huzhi Zheng
Keyword(s):  
Quantum Dots ◽  
Prion Protein ◽  
Cdte Quantum Dots ◽  
Size Dependent

rPrP can be applied to separate quantum dots with different size.

scholarly journals Experimental Transmission of the Chronic Wasting Disease Agent to Swine after Oral or Intracranial Inoculation

2017 ◽  
Vol 91 (19) ◽  
Author(s):  
S. Jo Moore ◽  
M. Heather West Greenlee ◽  
Naveen Kondru ◽  
Sireesha Manne ◽  
Jodi D. Smith ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Chronic Wasting Disease ◽  
Mouse Bioassay ◽  
Lymphoid Tissues ◽  
Species Barrier ◽  
Wasting Disease ◽  
Disease Agent ◽  
Domestic Swine

ABSTRACT Chronic wasting disease (CWD) is a naturally occurring, fatal neurodegenerative disease of cervids. The potential for swine to serve as hosts for the agent of CWD is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation. Crossbred piglets were assigned to three groups, intracranially inoculated (n = 20), orally inoculated (n = 19), and noninoculated (n = 9). At approximately the age at which commercial pigs reach market weight, half of the pigs in each group were culled (“market weight” groups). The remaining pigs (“aged” groups) were allowed to incubate for up to 73 months postinoculation (mpi). Tissues collected at necropsy were examined for disease-associated prion protein (PrPSc) by Western blotting (WB), antigen capture enzyme immunoassay (EIA), immunohistochemistry (IHC), and in vitro real-time quaking-induced conversion (RT-QuIC). Brain samples from selected pigs were also bioassayed in mice expressing porcine prion protein. Four intracranially inoculated aged pigs and one orally inoculated aged pig were positive by EIA, IHC, and/or WB. By RT-QuIC, PrPSc was detected in lymphoid and/or brain tissue from one or more pigs in each inoculated group. The bioassay was positive in four out of five pigs assayed. This study demonstrates that pigs can support low-level amplification of CWD prions, although the species barrier to CWD infection is relatively high. However, detection of infectivity in orally inoculated pigs with a mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity. IMPORTANCE We challenged domestic swine with the chronic wasting disease agent by inoculation directly into the brain (intracranially) or by oral gavage (orally). Disease-associated prion protein (PrPSc) was detected in brain and lymphoid tissues from intracranially and orally inoculated pigs as early as 8 months of age (6 months postinoculation). Only one pig developed clinical neurologic signs suggestive of prion disease. The amount of PrPSc in the brains and lymphoid tissues of positive pigs was small, especially in orally inoculated pigs. Regardless, positive results obtained with orally inoculated pigs suggest that it may be possible for swine to serve as a reservoir for prion disease under natural conditions.

scholarly journals Conformational Properties of Prion Strains Can Be Transmitted to Recombinant Prion Protein Fibrils in Real-Time Quaking-Induced Conversion

2014 ◽  
Vol 88 (20) ◽  
pp. 11791-11801 ◽  
Author(s):  
K. Sano ◽  
R. Atarashi ◽  
D. Ishibashi ◽  
T. Nakagaki ◽  
K. Satoh ◽  
...  
Keyword(s):  
Real Time ◽  
Prion Protein ◽  
Prion Strains ◽  
Protein Fibrils ◽  
Conformational Properties ◽  
Recombinant Prion Protein

scholarly journals Prion Strains and Transmission Barrier Phenomena

Pathogens ◽  
2018 ◽  
Vol 7 (1) ◽  
pp. 5 ◽  
Author(s):  
◽  
◽  
◽  
Keyword(s):  
Human Health ◽  
Current Knowledge ◽  
Species Barrier ◽  
Barrier Crossing ◽  
Prion Strain ◽  
Differential Selection ◽  
Physical Support ◽  
Prion Strains ◽  
Selection Of ◽  
Host Characteristics

Several experimental evidences show that prions are non-conventional pathogens, which physical support consists only in proteins. This finding raised questions regarding the observed prion strain-to-strain variations and the species barrier that happened to be crossed with dramatic consequences on human health and veterinary policies during the last 3 decades. This review presents a focus on a few advances in the field of prion structure and prion strains characterization: from the historical approaches that allowed the concept of prion strains to emerge, to the last results demonstrating that a prion strain may in fact be a combination of a few quasi species with subtle biophysical specificities. Then, we will focus on the current knowledge on the factors that impact species barrier strength and species barrier crossing. Finally, we present probable scenarios on how the interaction of strain properties with host characteristics may account for differential selection of new conformer variants and eventually species barrier crossing.

scholarly journals Increased Infectivity of Anchorless Mouse Scrapie Prions in Transgenic Mice Overexpressing Human Prion Protein

2015 ◽  
Vol 89 (11) ◽  
pp. 6022-6032 ◽  
Author(s):  
Brent Race ◽  
Katie Phillips ◽  
Kimberly Meade-White ◽  
James Striebel ◽  
Bruce Chesebro
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Transgenic Mice ◽  
Prion Protein ◽  
Prion Diseases ◽  
Human Species ◽  
Species Barrier ◽  
Gpi Anchor ◽  
Prion Infection ◽  
Barrier Model

ABSTRACTPrion protein (PrP) is found in all mammals, mostly as a glycoprotein anchored to the plasma membrane by a C-terminal glycosylphosphatidylinositol (GPI) linkage. Following prion infection, host protease-sensitive prion protein (PrPsen or PrPC) is converted into an abnormal, disease-associated, protease-resistant form (PrPres). Biochemical characteristics, such as the PrP amino acid sequence, and posttranslational modifications, such as glycosylation and GPI anchoring, can affect the transmissibility of prions as well as the biochemical properties of the PrPres generated. Previousin vivostudies on the effects of GPI anchoring on prion infectivity have not examined cross-species transmission. In this study, we tested the effect of lack of GPI anchoring on a species barrier model using mice expressing human PrP. In this model, anchorless 22L prions derived from tg44 mice were more infectious than 22L prions derived from C57BL/10 mice when tested in tg66 transgenic mice, which expressed wild-type anchored human PrP at 8- to 16-fold above normal. Thus, the lack of the GPI anchor on the PrPres from tg44 mice appeared to reduce the effect of the mouse-human PrP species barrier. In contrast, neither source of prions induced disease in tgRM transgenic mice, which expressed human PrP at 2- to 4-fold above normal.IMPORTANCEPrion protein (PrP) is found in all mammals, usually attached to cells by an anchor molecule called GPI. Following prion infection, PrP is converted into a disease-associated form (PrPres). While most prion diseases are species specific, this finding is not consistent, and species barriers differ in strength. The amino acid sequence of PrP varies among species, and this variability affects prion species barriers. However, other PrP modifications, including glycosylation and GPI anchoring, may also influence cross-species infectivity. We studied the effect of PrP GPI anchoring using a mouse-to-human species barrier model. Experiments showed that prions produced by mice expressing only anchorless PrP were more infectious than prions produced in mice expressing anchored PrP. Thus, the lack of the GPI anchor on prions reduced the effect of the mouse-human species barrier. Our results suggest that prion diseases that produce higher levels of anchorless PrP may pose an increased risk for cross-species infection.

On the concentration dependence of surface diffusion coefficients in capillary porous materials

1991 ◽  
Vol 434 (1891) ◽  
pp. 317-340 ◽  
Keyword(s):  
Experimental Data ◽  
Carbon Dioxide ◽  
Pore Size ◽  
Surface Diffusion ◽  
Diffusion Coefficients ◽  
Physical Adsorption ◽  
Structural Heterogeneity ◽  
Size Dependent ◽  
Chemical Potentials ◽  
Uniform Pore Size

The influence of structural heterogeneity, in the form of a non-uniform pore size distribution, on the isotherms and surface diffusion coefficients for monolayer physical adsorption is studied. A pore size dependent langmuirian isotherm is used along with consideration of equality of chemical potentials at the pore mouths at an intersection. The diffusion is modelled by a recently developed random walk formulation. It is found that the surface diffusion coefficients are strongly influenced by the heterogeneity and have a stronger increase with overall coverage than that predicted by the Darken equation. The results are found to match the experimental data of P. C. Carman and F. A. Raal on the diffusion of carbon dioxide in carbon black without the use of a fitting parameter.

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