scholarly journals Canine D163-PrP polymorphic variant does not provide complete protection against prion infection in small ruminant PrP context

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alba Marín-Moreno ◽  
Juan Carlos Espinosa ◽  
Patricia Aguilar-Calvo ◽  
Natalia Fernández-Borges ◽  
José Luis Pitarch ◽  
...  
Keyword(s):  
Small Ruminant ◽  
Protective Role ◽  
Classical Scrapie ◽  
Spongiform Encephalopathy ◽  
Effective Protection ◽  
Prion Strain ◽  
Prion Infection ◽  
Prion Strains ◽  
Classical Bovine Spongiform Encephalopathy

AbstractE/D163 polymorphism of dog prion protein (PrP) has been recently proposed as the variant responsible for canid prion resistance. To further investigate the protective role of this variant against prion replication, the transgenic mouse model OvPrP-Tg532 expressing sheep/goat PrP carrying the substitution D162 (equivalent to D163 position of dog PrP) was generated and intracranially inoculated with a broad collection of small ruminant prion strains. OvPrP-Tg532 mice showed resistance to classical bovine spongiform encephalopathy (BSE) from sheep and some classical scrapie isolates from sheep and goat but were susceptible to ovine atypical L-BSE and numerous classical scrapie isolates. Strikingly, some of these classical scrapie isolates showed a shift in their prion strain properties. These results suggest that other PrP residues apart from E/D163 variant of dog PrP or factors distinct than PrP may participate in prion resistance of canids and that different factors may be required for D162 sheep PrP to provide effective protection to sheep against ruminant prions.

scholarly journals Characterization of two distinct prion strains derived from bovine spongiform encephalopathy transmissions to inbred mice

2004 ◽  
Vol 85 (8) ◽  
pp. 2471-2478 ◽  
Author(s):  
Sarah E. Lloyd ◽  
Jacqueline M. Linehan ◽  
Melanie Desbruslais ◽  
Susan Joiner ◽  
Jennifer Buckell ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Incubation Time ◽  
Inbred Mice ◽  
Biochemical Properties ◽  
Distinct Pattern ◽  
Spongiform Encephalopathy ◽  
Prion Strain ◽  
Disease Phenotypes ◽  
Prion Strains

Distinct prion strains can be distinguished by differences in incubation period, neuropathology and biochemical properties of disease-associated prion protein (PrPSc) in inoculated mice. Reliable comparisons of mouse prion strain properties can only be achieved after passage in genetically identical mice, as host prion protein sequence and genetic background are known to modulate prion disease phenotypes. While multiple prion strains have been identified in sheep scrapie and Creutzfeldt–Jakob disease, bovine spongiform encephalopathy (BSE) is thought to be caused by a single prion strain. Primary passage of BSE prions to different lines of inbred mice resulted in the propagation of two distinct PrPSc types, suggesting that two prion strains may have been isolated. To investigate this further, these isolates were subpassaged in a single line of inbred mice (SJL) and it was confirmed that two distinct prion strains had been identified. MRC1 was characterized by a short incubation time (110±3 days), a mono-glycosylated-dominant PrPSc type and a generalized diffuse pattern of PrP-immunoreactive deposits, while MRC2 displayed a much longer incubation time (155±1 days), a di-glycosylated-dominant PrPSc type and a distinct pattern of PrP-immunoreactive deposits and neuronal loss. These data indicate a crucial involvement of the host genome in modulating prion strain selection and propagation in mice. It is possible that multiple disease phenotypes may also be possible in BSE prion infection in humans and other animals.

scholarly journals Protective Role of Interferon Regulatory Factor 3-Mediated Signaling against Prion Infection

2012 ◽  
Vol 86 (9) ◽  
pp. 4947-4955 ◽  
Author(s):  
D. Ishibashi ◽  
R. Atarashi ◽  
T. Fuse ◽  
T. Nakagaki ◽  
N. Yamaguchi ◽  
...  
Keyword(s):  
Interferon Regulatory Factor ◽  
Protective Role ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3 ◽  
Prion Infection

scholarly journals Protective role of MyD88-independent innate immune responses against prion infection

Prion ◽  
2012 ◽  
Vol 6 (5) ◽  
pp. 443-446 ◽  
Author(s):  
Daisuke Ishibashi ◽  
Ryuichiro Atarashi ◽  
Noriyuki Nishida
Keyword(s):  
Immune Responses ◽  
Protective Role ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Prion Infection

scholarly journals Porcine Prion Protein as a Paradigm of Limited Susceptibility to Prion Strain Propagation

2020 ◽  
Author(s):  
Juan Carlos Espinosa ◽  
Alba Marín-Moreno ◽  
Patricia Aguilar-Calvo ◽  
Sylvie L Benestad ◽  
Olivier Andreoletti ◽  
...  
Keyword(s):  
Prion Protein ◽  
Protein Misfolding ◽  
Prion Diseases ◽  
Conformational Flexibility ◽  
Cellular Prion Protein ◽  
Spongiform Encephalopathy ◽  
Prion Strain ◽  
Experimental Transmission ◽  
Prion Strains ◽  
Jakob Disease

Abstract Although experimental transmission of bovine spongiform encephalopathy (BSE) to pigs and transgenic mice expressing pig cellular prion protein (PrPC) (porcine PrP [PoPrP]–Tg001) has been described, no natural cases of prion diseases in pig were reported. This study analyzed pig-PrPC susceptibility to different prion strains using PoPrP-Tg001 mice either as animal bioassay or as substrate for protein misfolding cyclic amplification (PMCA). A panel of isolates representatives of different prion strains was selected, including classic and atypical/Nor98 scrapie, atypical-BSE, rodent scrapie, human Creutzfeldt-Jakob-disease and classic BSE from different species. Bioassay proved that PoPrP-Tg001-mice were susceptible only to the classic BSE agent, and PMCA results indicate that only classic BSE can convert pig-PrPC into scrapie-type PrP (PrPSc), independently of the species origin. Therefore, conformational flexibility constraints associated with pig-PrP would limit the number of permissible PrPSc conformations compatible with pig-PrPC, thus suggesting that pig-PrPC may constitute a paradigm of low conformational flexibility that could confer high resistance to the diversity of prion strains.

scholarly journals Extraneural Prion Neuroinvasion without Lymphoreticular System Infection

2005 ◽  
Vol 79 (18) ◽  
pp. 11858-11863 ◽  
Author(s):  
Jason C. Bartz ◽  
Crista DeJoia ◽  
Tammy Tucker ◽  
Anthony E. Kincaid ◽  
Richard A. Bessen
Keyword(s):  
Lymph Nodes ◽  
Prion Disease ◽  
Prion Diseases ◽  
Cranial Nerves ◽  
Clinical Disease ◽  
Spongiform Encephalopathy ◽  
Peripheral Tissues ◽  
Prion Infection ◽  
Spleen And Lymph Nodes

ABSTRACT While prion infection of the lymphoreticular system (LRS) is necessary for neuroinvasion in many prion diseases, in bovine spongiform encephalopathy and atypical cases of sheep scrapie there is evidence to challenge that LRS infection is required for neuroinvasion. Here we investigated the role of prion infection of LRS tissues in neuroinvasion following extraneural inoculation with the HY and DY strains of the transmissible mink encephalopathy (TME) agent. DY TME agent infectivity was not detected in spleen or lymph nodes following intraperitoneal inoculation and clinical disease was not observed following inoculation into the peritoneum or lymph nodes, or after oral ingestion. In contrast, inoculation of the HY TME agent by each of these peripheral routes resulted in replication in the spleen and lymph nodes and induced clinical disease. To clarify the role of the LRS in neuroinvasion, the HY and DY TME agents were also inoculated into the tongue because it is densely innervated and lesions on the tongue, which are common in ruminants, increase the susceptibility of hamsters to experimental prion disease. Following intratongue inoculation, the DY TME agent caused prion disease and was detected in both the tongue and brainstem nuclei that innervate the tongue, but the prion protein PrPSc was not detected in the spleen or lymph nodes. These findings indicate that the DY TME agent can spread from the tongue to the brain along cranial nerves and neuroinvasion does not require agent replication in the LRS. These studies provide support for prion neuroinvasion from highly innervated peripheral tissues in the absence of LRS infection in natural prion diseases of livestock.

scholarly journals Detection of Atypical H-Type Bovine Spongiform Encephalopathy and Discrimination of Bovine Prion Strains by Real-Time Quaking-Induced Conversion

2016 ◽  
Vol 54 (3) ◽  
pp. 676-686 ◽  
Author(s):  
Kentaro Masujin ◽  
Christina D. Orrú ◽  
Kohtaro Miyazawa ◽  
Bradley R. Groveman ◽  
Lynne D. Raymond ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Real Time ◽  
Prion Diseases ◽  
Proteinase K ◽  
Spongiform Encephalopathy ◽  
Reaction Products ◽  
Protein Substrates ◽  
Prion Strains ◽  
Recombinant Prion Protein ◽  
Classical Bovine Spongiform Encephalopathy

Prion diseases of cattle include the classical bovine spongiform encephalopathy (C-BSE) and the atypical H-type BSE (H-BSE) and L-type BSE (L-BSE) strains. Although the C- and L-BSE strains can be detected and discriminated by ultrasensitive real-time quaking-induced conversion (RT-QuIC) assays, no such test has yet been described for the detection of H-BSE or the discrimination of each of the major bovine prion strains. Here, we demonstrate an RT-QuIC assay for H-BSE that can detect as little as 10−9dilutions of brain tissue and neat cerebrospinal fluid samples from clinically affected cattle. Moreover, comparisons of the reactivities with different recombinant prion protein substrates and/or immunoblot band profiles of proteinase K-treated RT-QuIC reaction products indicated that H-, L-, and C-BSE have distinctive prion seeding activities and can be discriminated by RT-QuIC on this basis.

scholarly journals Classical scrapie in small ruminants is caused by at least four different prion strains

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Alba Marín-Moreno ◽  
Patricia Aguilar-Calvo ◽  
Juan Carlos Espinosa ◽  
María Zamora-Ceballos ◽  
José Luis Pitarch ◽  
...  
Keyword(s):  
Transmissible Spongiform Encephalopathy ◽  
Small Ruminants ◽  
Classical Scrapie ◽  
Spongiform Encephalopathy ◽  
Rodent Models ◽  
Species Barrier ◽  
Single Strain ◽  
Prion Strains ◽  
Scrapie Strains

AbstractThe diversity of goat scrapie strains in Europe has recently been studied using bioassays in a wide collection of rodent models, resulting in the classification of classical scrapie into four different categories. However, the sole use of the first passage does not lead to isolate adaptation and identification of the strains involved and might therefore lead to misclassification of some scrapie isolates. Therefore, this work reports the complete transmission study of a wide collection of goat transmissible spongiform encephalopathy (TSE) isolates by intracranial inoculation in two transgenic mouse lines overexpressing either small ruminant (TgGoat-ARQ) or bovine (TgBov) PrPC. To compare scrapie strains in sheep and goats, sheep scrapie isolates from different European countries were also included in the study. Once the species barrier phenomenon was overcome, an accurate classification of the isolates was attained. Thus, the use of just two rodent models allowed us to fully differentiate at least four different classical scrapie strains in small ruminants and to identify isolates containing mixtures of strains. This work reinforces the idea that classical scrapie in small ruminants is a prion disease caused by multiple different prion strains and not by a single strain, as is the case for epidemic classical bovine spongiform encephalopathy (BSE-C). In addition, the clear dissimilarity between the different scrapie strains and BSE-C does not support the idea that classical scrapie is the origin of epidemic BSE-C.

Protective role of peroxiredoxin-4 in heart failure

2020 ◽  
Vol 134 (1) ◽  
pp. 71-72
Author(s):  
Naseer Ahmed ◽  
Masooma Naseem ◽  
Javeria Farooq
Keyword(s):  
Heart Failure ◽  
Cardiac Fibroblasts ◽  
Protective Role ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Total Antioxidant ◽  
Galectin 3 ◽  
Consequent Increase ◽  
And Oxidative Stress

Abstract Recently, we have read with great interest the article published by Ibarrola et al. (Clin. Sci. (Lond.) (2018) 132, 1471–1485), which used proteomics and immunodetection methods to show that Galectin-3 (Gal-3) down-regulated the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. Authors concluded that ‘antioxidant activity of Prx-4 had been identified as a protein down-regulated by Gal-3. Moreover, Gal-3 induced a decrease in total antioxidant capacity which resulted in a consequent increase in peroxide levels and oxidative stress markers in cardiac fibroblasts.’ We would like to point out some results stated in the article that need further investigation and more detailed discussion to clarify certain factors involved in the protective role of Prx-4 in heart failure.

Parenting Behaviors and Anxiety in Young Adults

2015 ◽  
Vol 36 (3) ◽  
pp. 170-176 ◽  
Author(s):  
Erin N. Stevens ◽  
Joseph R. Bardeen ◽  
Kyle W. Murdock
Keyword(s):  
Effortful Control ◽  
Parenting Behaviors ◽  
Protective Role ◽  
Anxiety Symptoms ◽  
Interactive Effects ◽  
Parental Overprotection ◽  
High Control ◽  
Development Of Anxiety ◽  
The Relationship

Parenting behaviors – specifically behaviors characterized by high control, intrusiveness, rejection, and overprotection – and effortful control have each been implicated in the development of anxiety pathology. However, little research has examined the protective role of effortful control in the relation between parenting and anxiety symptoms, specifically among adults. Thus, we sought to explore the unique and interactive effects of parenting and effortful control on anxiety among adults (N = 162). Results suggest that effortful control uniquely contributes to anxiety symptoms above and beyond that of any parenting behavior. Furthermore, effortful control acted as a moderator of the relationship between parental overprotection and anxiety, such that overprotection is associated with anxiety only in individuals with lower levels of effortful control. Implications for potential prevention and intervention efforts which specifically target effortful control are discussed. These findings underscore the importance of considering individual differences in self-regulatory abilities when examining associations between putative early-life risk factors, such as parenting, and anxiety symptoms.

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