Synthetic Scrapie Infectivity: Interaction between Recombinant PrP and Scrapie Brain-Derived RNA

被引：11

作者：

Simoneau, Steve ^{[1
]}

Thomzig, Achim ^{[2
]}

Ruchoux, Marie-Madeleine ^{[1
]}

Vignier, Nicolas ^{[3
]}

Daus, Martin L. ^{[2
]}

Poleggi, Anna ^{[4
]}

Lebon, Pierre ^{[5
]}

Freire, Sophie ^{[1
]}

Durand, Valerie ^{[1
]}

Graziano, Silvia ^{[4
]}

Galeno, Roberta ^{[4
]}

Cardone, Franco ^{[4
]}

Comoy, Emmanuel ^{[1
]}

Pocchiari, Maurizio ^{[4
]}

Beekes, Michael ^{[2
]}

Deslys, Jean-Philippe ^{[1
]}

Fournier, Jean-Guy ^{[1
]}

机构：

[1] CEA, Inst Emerging Dis & Innovat Therapies iMETI, Div Prions & Related Dis SEPIA, Fontenay Aux Roses, France

[2] Robert Koch Inst, ZBS Prote & Spect Prions & Prionoids Res Unit 6, Berlin, Germany

[3] Hop La Pitie Salpetriere, Inst Myol, CNRS, INSERM,UMRS 7215,U974, Paris, France

[4] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy

[5] Hop Cochin St Vincent de Paul, AP HP, Virol Lab, Paris, France

来源：

VIRULENCE | 2015年 / 6卷 / 02期

关键词：

nature of prions; PMCA; prions; prion infectivity; PrPsc; recombinant PrP; RNA; SAF-derived RNA; scrapie infectivity; CREUTZFELDT-JAKOB-DISEASE; INFECTED HAMSTER BRAIN; PRION PROTEIN; MAMMALIAN PRIONS; NUCLEIC-ACID; ACCUMULATION; REPLICATION; PARTICLES; MOLECULES; FIBRILS;

D O I：

10.4161/21505594.2014.989795

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The key molecular event in human cerebral proteinopathies, which include Alzheimer's, Parkinson's and Huntington's diseases, is the structural conversion of a specific host protein into a -sheet-rich conformer. With regards to this common mechanism, it appears difficult to explain the outstanding infectious properties attributed to PrPSc, the hallmark of another intriguing family of cerebral proteinopathies known as transmissible spongiform encephalopathies (TSE) or prion diseases. The infectious PrPSc or "prion" is thought to be composed solely of a misfolded form of the otherwise harmless cellular prion protein (PrPc). To gain insight into this unique situation, we used the 263K scrapie hamster model to search for a putative PrPSc-associated factor that contributes to the infectivity of PrPSc amyloid. In a rigorously controlled set of experiments that included several bioassays, we showed that originally innocuous recombinant prion protein (recPrP) equivalent to PrPc is capable of initiating prion disease in hamsters when it is converted to a prion-like conformation (-sheet-rich) in the presence of RNA purified from scrapie-associated fibril (SAF) preparations. Analysis of the recPrP-RNA infectious mixture reveals the presence of 2 populations of small RNAs of approximately 27 and 55 nucleotides. These unprecedented findings are discussed in light of the distinct relationship that may exist between this RNA material and the 2 biological properties, infectivity and strain features, attributed to prion amyloid.

引用

页码：132 / 144

页数：13