مورد إلكتروني
Prions from Sporadic Creutzfeldt-Jakob Disease Patients Propagate as Strain Mixtures
| العنوان: | Prions from Sporadic Creutzfeldt-Jakob Disease Patients Propagate as Strain Mixtures |
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| المؤلفون: | European Commission, Food Standards Agency (UK), Ministerio de Economía y Competitividad (España), CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Cassard, Hervé [0000-0001-8651-6179], Huor, Alvina [0000-0002-5598-9958], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Douet, Jean-Yves [0000-0002-0426-4957], Vilette, Didier [0000-0001-8429-9916], Delisle, Marie-Bernadette [0000-0002-8254-7047], Marín-Moreno, Alba [0000-0002-4023-6398], Peran, Patrice [0000-0001-7200-0139], Béringue, V. [0000-0001-6706-5712], Torres, Juan María [0000-0003-0443-9232], Ironside, James W. [0000-0001-5869-2108], Andréoletti, Olivier [0000-0002-7369-6016], Cassard, Hervé, Huor, Alvina, Espinosa Martín, Juan Carlos, Douet, Jean-Yves, Lugan, Séverine, Aron, Naima, Vilette, Didier, Delisle, Marie-Bernadette, Marín-Moreno, Alba, Peran, Patrice, Béringue, V., Torres, Juan María, Ironside, James W., Andréoletti, Olivier |
| بيانات النشر: | American Society for Microbiology 2020-06-16 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently classified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K-digested abnormal prion protein (PrPres) isoform identified by Western blotting (type 1 or type 2). Converging evidence led to the view that MM/MV1, VV/MV2, and VV1 and MM2 sCJD cases are caused by distinct prion strains. However, in a significant proportion of sCJD patients, both type 1 and type 2 PrPres were reported to accumulate in the brain, which raised questions about the diversity of sCJD prion strains and the coexistence of two prion strains in the same patient. In this study, a panel of sCJD brain isolates (n = 29) that displayed either a single or mixed type 1/type 2 PrPres were transmitted into human-PrP-expressing mice (tgHu). These bioassays demonstrated that two distinct prion strains (M1CJD and V2CJD) were associated with the development of sCJD in MM1/MV1 and VV2/MV2 patients. However, in about 35% of the investigated VV and MV cases, transmission results were consistent with the presence of both M1CJD and V2CJD strains, including in patients who displayed a "pure" type 1 or type 2 PrPres The use of a highly sensitive prion in vitro amplification technique that specifically probes the V2CJD strain revealed the presence of the V2CJD prion in more than 80% of the investigated isolates, including isolates that propagated as a pure M1CJD strain in tgHu. These results demonstrate that at least two sCJD prion strains can be present in a single patient.IMPORTANCE sCJD occurrence is currently assumed to result from spontaneous and stochastic formation of a misfolded PrP nucleus in the brains of affected patients. This original nucleus then recruits and converts nascent PrPC into PrPSc, leading to the propagation of prions in the patient's brain. Our study demonstrates the coexistence of two prion strains in the brains of a majority of the 23 sCJD patients investigated. The relative propor |
| مصطلحات الفهرس: | Diversity, Evolution, Prion, Prions, sCJD, Sporadic Creutzfeldt-Jakob disease, Strain diversity, Strains, artículo |
| URL: | Centro de Investigación en Sanidad Animal (CISA) Publisher's version Sí info:eu-repo/grantAgreement/EC/EFA282/13 info:eu-repo/grantAgreement/EC/EFA148/16 info:eu-repo/grantAgreement/EC/222887 info:eu-repo/grantAgreement/MINECO/AGL2016-78054-R |
| الإتاحة: | Open access content. Open access content https://creativecommons.org/licenses/by/4.0 openAccess |
| ملاحظة: | English |
| أرقام أخرى: | CTK oai:digital.csic.es:10261/340815 mBio 11(3): 1-19 (2020) 2161-2129 10.1128/mBio.00393-20 2150-7511 32546613 2-s2.0-85086685521 1416002795 |
| المصدر المساهم: | CSIC From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1416002795 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |