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Copyright: CNRS Photothèque
Photographe: MELKI Ronald
Laboratoire: UPR9063 – LABORATOIRE D’ENZYMOLOGIE ET BIOCHIMIE STRUCTURALES (LEBS) – GIF-SUR-YVETTE
Légende: Fibres que forme le prion lorsqu’il devient transmissible. Cette image a été obtenue par microscopie électronique à la suite du changement transmissible reproduit dans un tube à essai dans le laboratoire. Ces fibres sont identiques aux fibres retrouvées dans le cerveau de personnes atteintes de la maladie de Creutzfeldt-Jakob.
When prions are transferred from one species to another—like from sheep and cows to mice in the laboratory or to humans in the case of the fatally neurodegenerative variant Creutzfeldt-Jakob disease—new forms of the infectious proteins can emerge over time that make them deadly to the new host. A new study examines the emergence and persistence of prion mutations, which allow prions to grow in infected cells in the presence of anti-prion compounds. …
Darwinian Evolution of Prions in Cell Culture
Jiali Li, Shawn Browning, Sukhvir P. Mahal, Anja M. Oelschlegel, Charles Weissmann*
Prions are infectious proteins consisting mainly of PrPSc, a β sheet–rich conformer of the normal host protein PrPC, and occur in different strains. Strain identity is thought to beencoded by PrPSc conformation.We found that biologically cloned prion populations gradually became heterogene ous by accumulating “mutants,” and selective pressures resulted in the emergence : of different mutants as major constituents of the evolving population. Thus, when transferred from brain to cultured cells, “cell-adapted” prions outcompeted their “brain-adapted” counterparts, and the opposite occurred when prions were returned from cells to brain. Similarly, the inhibitor swainsonine selected for a resistant substrain, whereas, in its absence, the susceptible substrain outgrew its resistant counterpart. Prions, albeit devoid of a nucleic acid genome, are thus subject to mutation and selective amplification.