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3.
Rev Chilena Infectol ; 37(2): 163-169, 2020 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-32730483

RESUMO

From the scrapie of the sheep to the bovine spongiform encephalitis, and from the kuru to the Creutzfeldt-Jakob disease, tenacious investigators searched for the mysterious agent of these neurological disorders, till Stanley Prusiner discovered and described the prion in the eighties, wining the Nobel Prize in 1997. But this was not the end of the fantastic history of the incredible protein designed prion by Prusiner, because now the investigation on neuroscience has founded prion-like proteins playing an important role in the genesis of the long-term memory.


Assuntos
Doenças Priônicas , Animais , Bovinos , Prêmio Nobel , Príons , Scrapie , Ovinos
4.
PLoS Biol ; 18(6): e3000725, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32516343

RESUMO

Inherited prion diseases are caused by autosomal dominant coding mutations in the human prion protein (PrP) gene (PRNP) and account for about 15% of human prion disease cases worldwide. The proposed mechanism is that the mutation predisposes to conformational change in the expressed protein, leading to the generation of disease-related multichain PrP assemblies that propagate by seeded protein misfolding. Despite considerable experimental support for this hypothesis, to-date spontaneous formation of disease-relevant, transmissible PrP assemblies in transgenic models expressing only mutant human PrP has not been demonstrated. Here, we report findings from transgenic mice that express human PrP 117V on a mouse PrP null background (117VV Tg30 mice), which model the PRNP A117V mutation causing inherited prion disease (IPD) including Gerstmann-Sträussler-Scheinker (GSS) disease phenotypes in humans. By studying brain samples from uninoculated groups of mice, we discovered that some mice (≥475 days old) spontaneously generated abnormal PrP assemblies, which after inoculation into further groups of 117VV Tg30 mice, produced a molecular and neuropathological phenotype congruent with that seen after transmission of brain isolates from IPD A117V patients to the same mice. To the best of our knowledge, the 117VV Tg30 mouse line is the first transgenic model expressing only mutant human PrP to show spontaneous generation of transmissible PrP assemblies that directly mirror those generated in an inherited prion disease in humans.


Assuntos
Amiloide/metabolismo , Príons/metabolismo , Adulto , Envelhecimento/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Códon/genética , Heterozigoto , Homozigoto , Humanos , Camundongos Transgênicos , Pessoa de Meia-Idade , Príons/isolamento & purificação
5.
PLoS Biol ; 18(6): e3000754, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32584805

RESUMO

The prion protein, PrP, can adopt at least 2 conformations, the overwhelmingly prevalent cellular conformation (PrPC) and the scrapie conformation (PrPSc). PrPC features a globular C-terminal domain containing 3 α-helices and a short ß-sheet and a long flexible N-terminal tail whose exact conformation in vivo is not yet known and a metastable subdomain with ß-strand propensity has been identified within it. The PrPSc conformation is very rare and has the characteristics of an amyloid. Furthermore, PrPSc is a prion, i.e., it is infectious. This involves 2 steps: (1) PrPSc can template PrPC and coerce it to adopt the PrPSc conformation and (2) PrPSc can be transmitted between individuals, by oral, parenteral, and other routes and thus propagate as an infectious agent. However, this is a simplification: On the one hand, PrPSc is not a single conformation, but rather, a set of alternative similar but distinct conformations. Furthermore, other amyloid conformations of PrP exist with different biochemical and propagative properties. In this issue of PLOS Biology, Asante and colleagues describe the first murine model of familial human prion disease and demonstrate the emergence and propagation of 2 PrP amyloid conformers. Of these, one causes neurodegeneration, whereas the other does not. With its many conformers, PrP is a truly protean protein.


Assuntos
Doenças Priônicas , Príons , Scrapie , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Transgênicos , Proteínas Priônicas
6.
PLoS Pathog ; 16(4): e1008495, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32294141

RESUMO

Prion diseases are caused by the misfolding of a host-encoded glycoprotein, PrPC, into a pathogenic conformer, PrPSc. Infectious prions can exist as different strains, composed of unique conformations of PrPSc that generate strain-specific biological traits, including distinctive patterns of PrPSc accumulation throughout the brain. Prion strains from different animal species display different cofactor and PrPC glycoform preferences to propagate efficiently in vitro, but it is unknown whether these molecular preferences are specified by the amino acid sequence of PrPC substrate or by the conformation of PrPSc seed. To distinguish between these two possibilities, we used bank vole PrPC to propagate both hamster or mouse prions (which have distinct cofactor and glycosylation preferences) with a single, common substrate. We performed reconstituted sPMCA reactions using either (1) phospholipid or RNA cofactor molecules, or (2) di- or un-glycosylated bank vole PrPC substrate. We found that prion strains from either species are capable of propagating efficiently using bank vole PrPC substrates when reactions contained the same PrPC glycoform or cofactor molecule preferred by the PrPSc seed in its host species. Thus, we conclude that it is the conformation of the input PrPSc seed, not the amino acid sequence of the PrPC substrate, that primarily determines species-specific cofactor and glycosylation preferences. These results support the hypothesis that strain-specific patterns of prion neurotropism are generated by selection of differentially distributed cofactors molecules and/or PrPC glycoforms during prion replication.


Assuntos
Proteínas PrPC/metabolismo , Doenças Priônicas/metabolismo , Príons/metabolismo , Sequência de Aminoácidos , Animais , Arvicolinae , Encéfalo/patologia , Doenças Transmissíveis/metabolismo , Cricetinae , Glicosilação , Mesocricetus , Camundongos , Camundongos Endogâmicos C57BL , Conformação Molecular , Proteínas PrPSc/metabolismo , Especificidade da Espécie
8.
Proc Natl Acad Sci U S A ; 117(11): 5826-5835, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32127480

RESUMO

Mutations in a number of stress granule-associated proteins have been linked to various neurodegenerative diseases. Several of these mutations are found in aggregation-prone prion-like domains (PrLDs) within these proteins. In this work, we examine the sequence features governing PrLD localization to stress granules upon stress. We demonstrate that many yeast PrLDs are sufficient for stress-induced assembly into microscopically visible foci that colocalize with stress granule markers. Additionally, compositional biases exist among PrLDs that assemble upon stress, and these biases are consistent across different stressors. Using these biases, we have developed a composition-based prediction method that accurately predicts PrLD assembly into foci upon heat shock. We show that compositional changes alter PrLD assembly behavior in a predictable manner, while scrambling primary sequence has little effect on PrLD assembly and recruitment to stress granules. Furthermore, we were able to design synthetic PrLDs that were efficiently recruited to stress granules, and found that aromatic amino acids, which have previously been linked to PrLD phase separation, were dispensable for this recruitment. These results highlight the flexible sequence requirements for stress granule recruitment and suggest that PrLD localization to stress granules is driven primarily by amino acid composition, rather than primary sequence.


Assuntos
Grânulos Citoplasmáticos/metabolismo , Proteínas Priônicas/química , Domínios Proteicos , Estresse Fisiológico/fisiologia , Composição de Bases , Proteínas de Choque Térmico/metabolismo , Mutação , Doenças Neurodegenerativas/metabolismo , Proteínas Priônicas/genética , Proteínas Priônicas/metabolismo , Príons/metabolismo , Saccharomyces cerevisiae/metabolismo , Análise de Sequência de Proteína , Azida Sódica/farmacologia , Estresse Fisiológico/genética
9.
PLoS One ; 15(3): e0229796, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32134970

RESUMO

Chaperones and autophagy are components of the protein quality control system that contribute to the management of proteins that are misfolded and aggregated. Here, we use yeast prions, which are self-perpetuating aggregating proteins, as a means to understand how these protein quality control systems influence aggregate loss. Chaperones, such as Hsp104, fragment prion aggregates to generate more prion seeds for propagation. While much is known about the role of chaperones, little is known about how other quality control systems contribute to prion propagation. We show that the aprotic solvent dimethyl sulfoxide (DMSO) cures a range of [PSI+] prion variants, which are related to several misfolded aggregated conformations of the Sup35 protein. Our studies show that DMSO-mediated curing is quicker and more efficient than guanidine hydrochloride, a prion curing agent that inactivates the Hsp104 chaperone. Instead, DMSO appears to induce Hsp104 expression. Using the yTRAP system, a recently developed transcriptional reporting system for tracking protein solubility, we found that DMSO also rapidly induces the accumulation of soluble Sup35 protein, suggesting a potential link between Hsp104 expression and disassembly of Sup35 from the prion aggregate. However, DMSO-mediated curing appears to also be associated with other quality control systems. While the induction of autophagy alone does not lead to curing, we found that DMSO-mediated curing is dramatically impaired in autophagy related (atg) gene mutants, suggesting that other factors influence this DMSO mechanism of curing. Our data suggest that DMSO-mediated curing is not simply dependent upon Hsp104 overexpression alone, but may further depend upon other aspects of proteostasis.


Assuntos
Proteínas Relacionadas à Autofagia/genética , Dimetil Sulfóxido/farmacologia , Proteínas de Choque Térmico/metabolismo , Fatores de Terminação de Peptídeos/metabolismo , Príons/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Proteínas de Choque Térmico/genética , Mutação , Fatores de Terminação de Peptídeos/antagonistas & inibidores , Príons/antagonistas & inibidores , Agregados Proteicos/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores , Proteínas de Saccharomyces cerevisiae/genética , Solubilidade/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
10.
PLoS One ; 15(3): e0227094, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126066

RESUMO

CWD is an emergent prion disease that now affects cervid species on three continents. CWD is efficiently spread in wild and captive populations, likely through both direct animal contact and environmental contamination. Here, by longitudinally assaying in feces of CWD-exposed white-tailed deer by RT-QuIC, we demonstrate fecal shedding of prion seeding activity months before onset of clinical symptoms and continuing throughout the disease course. We also examine the impact of simulated environmental conditions such as repeated freeze-thaw cycles and desiccation on fecal prion seeding activity. We found that while multiple (n = 7) freeze-thaw cycles substantially decreased fecal seeding activity, desiccation had little to no effect on seeding activity. Finally, we examined whether RT-QuIC testing of landscape fecal deposits could distinguish two premises with substantial known CWD prevalence from one in which no CWD-infected animals had been detected. In the above pilot study, this distinction was possible. We conclude that fecal shedding of CWD prions occurs over much of the disease course, that environmental factors influence prion seeding activity, and that it is feasible to detect fecal prion contamination using RT-QuIC.


Assuntos
Bioensaio/métodos , Cervos , Fezes/química , Príons/análise , Doença de Emaciação Crônica/diagnóstico , Animais , Exposição Ambiental/efeitos adversos , Estudos de Viabilidade , Prevalência , Doença de Emaciação Crônica/epidemiologia , Doença de Emaciação Crônica/transmissão
12.
Viruses ; 12(3)2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32150831

RESUMO

I would like to comment on an unsupported charge published in Viruses [...].


Assuntos
Kuru , Príons , Vírus , Humanos
13.
Mol Cell Biol ; 40(12)2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32205407

RESUMO

Maintenance of protein homeostasis in eukaryotes under normal growth and stress conditions requires the functions of Hsp70 chaperones and associated cochaperones. Here, we investigate an evolutionarily conserved serine phosphorylation that occurs at the site of communication between the nucleotide-binding and substrate-binding domains of Hsp70. Ser151 phosphorylation in yeast Hsp70 (Ssa1) is promoted by cyclin-dependent kinase (Cdk1) during normal growth. Phosphomimetic substitutions at this site (S151D) dramatically downregulate heat shock responses, a result conserved with HSC70 S153 in human cells. Phosphomimetic forms of Ssa1 also fail to relocalize in response to starvation conditions, do not associate in vivo with Hsp40 cochaperones Ydj1 and Sis1, and do not catalyze refolding of denatured proteins in vitro in cooperation with Ydj1 and Hsp104. Despite these negative effects on HSC70/HSP70 function, the S151D phosphomimetic allele promotes survival of heavy metal exposure and suppresses the Sup35-dependent [PSI+ ] prion phenotype, consistent with proposed roles for Ssa1 and Hsp104 in generating self-nucleating seeds of misfolded proteins. Taken together, these results suggest that Cdk1 can downregulate Hsp70 function through phosphorylation of this site, with potential costs to overall chaperone efficiency but also advantages with respect to reduction of metal-induced and prion-dependent protein aggregate production.


Assuntos
Adenosina Trifosfatases/metabolismo , Proteínas de Choque Térmico HSC70/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Príons/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Adenosina Trifosfatases/química , Sítios de Ligação , Linhagem Celular , Proteínas de Choque Térmico HSC70/química , Proteínas de Choque Térmico HSP70/química , Humanos , Metais Pesados/metabolismo , Fosforilação , Agregados Proteicos , Desnaturação Proteica , Domínios Proteicos , Dobramento de Proteína , Proteostase , Saccharomyces cerevisiae/crescimento & desenvolvimento , Proteínas de Saccharomyces cerevisiae/química , Estresse Fisiológico
14.
Lancet Neurol ; 19(4): 361-368, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32199098

RESUMO

Prion disease is a rare, fatal, and exceptionally rapid neurodegenerative disease. Although incurable, prion disease follows a clear pathogenic mechanism, in which a single gene gives rise to a single prion protein (PrP) capable of converting into the sole causal disease agent, the misfolded prion. As efforts progress to leverage this mechanistic knowledge toward rational therapies, a principal challenge will be the design of clinical trials. Previous trials in prion disease have been done in symptomatic patients who are often profoundly debilitated at enrolment. About 15% of prion disease cases are genetic, creating an opportunity for early therapeutic intervention to delay or prevent disease. Highly variable age of onset and absence of established prodromal biomarkers might render infeasible existing models for testing drugs before disease onset. Advancement of near-term targeted therapeutics could crucially depend on thoughtful design of rigorous presymptomatic trials.


Assuntos
Doenças Priônicas/diagnóstico , Doenças Priônicas/terapia , Animais , Biomarcadores , Humanos , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/terapia , Doenças Priônicas/genética , Proteínas Priônicas/genética , Príons
15.
Biochem J ; 477(4): 833-852, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32108870

RESUMO

Prion diseases are fatal transmissible neurodegenerative conditions of humans and animals that arise through neurotoxicity induced by PrP misfolding. The cellular and molecular mechanisms of prion-induced neurotoxicity remain undefined. Understanding these processes will underpin therapeutic and control strategies for human and animal prion diseases, respectively. Prion diseases are difficult to study in their natural hosts and require the use of tractable animal models. Here we used RNA-Seq-based transcriptome analysis of prion-exposed Drosophila to probe the mechanism of prion-induced neurotoxicity. Adult Drosophila transgenic for pan neuronal expression of ovine PrP targeted to the plasma membrane exhibit a neurotoxic phenotype evidenced by decreased locomotor activity after exposure to ovine prions at the larval stage. Pathway analysis and quantitative PCR of genes differentially expressed in prion-infected Drosophila revealed up-regulation of cell cycle activity and DNA damage response, followed by down-regulation of eIF2 and mTOR signalling. Mitochondrial dysfunction was identified as the principal toxicity pathway in prion-exposed PrP transgenic Drosophila. The transcriptomic changes we observed were specific to PrP targeted to the plasma membrane since these prion-induced gene expression changes were not evident in similarly treated Drosophila transgenic for cytosolic pan neuronal PrP expression, or in non-transgenic control flies. Collectively, our data indicate that aberrant cell cycle activity, repression of protein synthesis and altered mitochondrial function are key events involved in prion-induced neurotoxicity, and correlate with those identified in mammalian hosts undergoing prion disease. These studies highlight the use of PrP transgenic Drosophila as a genetically well-defined tractable host to study mammalian prion biology.


Assuntos
Modelos Animais de Doenças , Drosophila melanogaster/genética , Regulação da Expressão Gênica , Mitocôndrias/genética , Neurônios/metabolismo , Doenças Priônicas/patologia , Príons/toxicidade , Animais , Animais Geneticamente Modificados/genética , Animais Geneticamente Modificados/crescimento & desenvolvimento , Ciclo Celular , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/crescimento & desenvolvimento , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Neurônios/patologia , Fenótipo , Doenças Priônicas/induzido quimicamente , Doenças Priônicas/genética , Biossíntese de Proteínas , Transcriptoma
16.
Arch Biochem Biophys ; 683: 108319, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32101762

RESUMO

Eukaryotic double-ring chaperonin TRiC is an ATP-dependent protein-folding machine. Most of its substrates are known to form large ordered structures from multiple polypeptide chains. Since these structures are similar to fibrillar and oligomeric forms of amyloidogenic proteins, we hypothesized that TRiC may play a role in the development of neurodegenerative diseases of amyloid nature including prion diseases. Enzyme-linked immunosorbent assay showed that monomeric, oligomeric and fibrillar forms of prion protein (PrP) bind strongly to chaperonin TRiC, whereas glycation reduces the prion protein affinity for chaperonin. Nevertheless, dynamic light scattering, electron microscopy and thioflavin T fluorescence confirmed that all studied forms of PrP undergo an amyloid transformation after interaction with chaperonin, but different forms of prion protein are capable of having different effects on the functional state of TRiC. For example, prion protein monomers completely block its ability to reactivate the chaperonin's natural substrate - sperm-specific glyceraldehyde-3-phosphate dehydrogenase (GAPDS). At the same time, PrP oligomers and fibrils only partially prevent the reactivation of GAPDS upon the action of TRiC. The monomeric forms of prion protein glycated by methylglyoxal do not inhibit, but only slow down the chaperone-dependent reactivation of GAPDS. Thus, the interaction of amyloidogenic proteins with chaperonins could cause cell malfunction.


Assuntos
Chaperonina com TCP-1/química , Chaperoninas/química , Proteínas Priônicas/química , Amiloide/química , Animais , Benzotiazóis/química , Bovinos , Glicosilação , Humanos , Luz , Masculino , Microscopia Eletrônica , Doenças Neurodegenerativas/metabolismo , Príons/metabolismo , Ligação Proteica , Conformação Proteica , Dobramento de Proteína , Proteínas Recombinantes/química , Espalhamento de Radiação , Testículo/metabolismo
17.
Brain Nerve ; 72(2): 143-150, 2020 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-32036340

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Although the standard dopamine replacement therapy can alleviate motor symptoms, presently there is no available treatment to stop or reverse disease progression. Thus, there is an urgent need for the development of novel disease-modifying therapies to prevent the accumulation of cytotoxic α-synuclein (αS), a protein involved in PD pathogenesis, in the nervous system. Furthermore, emerging evidence suggests that the toxic αS species can move from one cell to another, thereby affecting the normal physiological state of the neighboring cells in a prion-like manner. The transmissible, extracellular αS is considered to be an ideal target for the disease-modifying treatments including antibody-based therapy. In this review, we will describe the molecular structure and functions of αS, its relevance to PD pathogenesis, and will discuss the current status and future perspectives of disease-modifying strategies targeting αS in PD.


Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , alfa-Sinucleína , Dopamina , Humanos , Doença de Parkinson/genética , Doença de Parkinson/terapia , Príons , alfa-Sinucleína/genética , alfa-Sinucleína/fisiologia
18.
Science ; 367(6478): 694-699, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32029630

RESUMO

Prion-like domains (PLDs) can drive liquid-liquid phase separation (LLPS) in cells. Using an integrative biophysical approach that includes nuclear magnetic resonance spectroscopy, small-angle x-ray scattering, and multiscale simulations, we have uncovered sequence features that determine the overall phase behavior of PLDs. We show that the numbers (valence) of aromatic residues in PLDs determine the extent of temperature-dependent compaction of individual molecules in dilute solutions. The valence of aromatic residues also determines full binodals that quantify concentrations of PLDs within coexisting dilute and dense phases as a function of temperature. We also show that uniform patterning of aromatic residues is a sequence feature that promotes LLPS while inhibiting aggregation. Our findings lead to the development of a numerical stickers-and-spacers model that enables predictions of full binodals of PLDs from their sequences.


Assuntos
Ribonucleoproteína Nuclear Heterogênea A1/química , Transição de Fase , Fenilalanina/química , Príons/química , Tirosina/química , Sequência de Aminoácidos , Espectroscopia de Ressonância Magnética , Domínios Proteicos , Espalhamento a Baixo Ângulo , Difração de Raios X
19.
Arch Virol ; 165(3): 535-556, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32025859

RESUMO

The existence of more than 30 strains of transmissible spongiform encephalopathy (TSE) and the paucity of infectivity of purified PrPSc, as well as considerations of PrP structure, are inconsistent with the protein-only (prion) theory of TSE. Nucleic acid is a strong contender as a second component. We juxtapose two key findings: (i) PrP is a nucleic-acid-binding antimicrobial protein that is similar to retroviral Gag proteins in its ability to trigger reverse transcription. (ii) Retroelement mobilization is widely seen in TSE disease. Given further evidence that PrP also mediates nucleic acid transport into and out of the cell, a strong case is to be made that a second element - retroelement nucleic acid - bound to PrP constitutes the second component necessary to explain the multiple strains of TSE.


Assuntos
Doenças Priônicas/patologia , Proteínas Priônicas/genética , Príons/genética , Animais , Humanos , Ácidos Nucleicos , Príons/fisiologia , Ligação Proteica , Retroelementos
20.
PLoS One ; 15(2): e0228327, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32059005

RESUMO

Chronic wasting disease (CWD) continues to spread or be recognized in the United States, Canada, and Europe. CWD is diagnosed by demonstration of the causative misfolded prion protein (PrPCWD) in either brain or lymphoid tissue using immunodetection methods, with immunohistochemistry (IHC) recognized as the gold standard. In recent years, in vitro amplification assays have been developed that can detect CWD prion seeding activity in tissues, excreta, and body fluids of affected cervids. These methods potentially offer earlier and more facile detection of CWD, both pre- and post-mortem. Here we provide a longitudinal profile of CWD infection progression, as assessed by both real-time quaking-induced conversion (RT-QuIC) and IHC on serial biopsies of mucosal lymphoid tissues of white-tailed deer orally exposed to low doses of CWD prions. We report that detection of CWD infection by RT-QuIC preceded that by IHC in both tonsil and recto-anal lymphoid tissue (RAMALT) in 14 of 19 deer (74%). Of the 322 biopsy samples collected in post-exposure longitudinal monitoring, positive RT-QuIC results were obtained for 146 samples, 91 of which (62%) were concurrently also IHC-positive. The lower frequency of IHC positivity was manifest most in the earlier post-exposure periods and in biopsies in which lymphoid follicles were not detected. For all deer in which RT-QuIC seeding activity was detected in a tonsil or RAMALT biopsy, PrPCWD was subsequently or concurrently detected by IHC. Overall, this study (a) provides a longitudinal profile of CWD infection in deer after low yet infectious oral prion exposure; (b) illustrates the value of RT-QuIC for sensitive detection of CWD; and (c) demonstrates an ultimate high degree of correlation between RT-QuIC and IHC positivity as CWD infection progresses.


Assuntos
Imuno-Histoquímica , Técnicas de Amplificação de Ácido Nucleico/métodos , Doença de Emaciação Crônica/patologia , Administração Oral , Animais , Cervos , Progressão da Doença , Estudos Longitudinais , Tecido Linfoide/metabolismo , Tecido Linfoide/patologia , Tonsila Palatina/metabolismo , Tonsila Palatina/patologia , Proteínas Priônicas/genética , Proteínas Priônicas/metabolismo , Príons/administração & dosagem , Doença de Emaciação Crônica/metabolismo
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