title: Infectious prion diseases in humans: cannibalism, iatrogenicity and zoonoses.
abstract: In contrast with other neurodegenerative disorders associated to protein misfolding, human prion diseases include infectious forms (also called transmitted forms) such as kuru, iatrogenic Creutzfeldt-Jakob disease and variant Creutzfeldt-Jakob disease. The transmissible agent is thought to be solely composed of the abnormal isoform (PrP(Sc)) of the host-encoded prion protein that accumulated in the central nervous system of affected individuals. Compared to its normal counterpart, PrP(Sc) is β-sheet enriched and aggregated and its propagation is based on an autocatalytic conversion process. Increasing evidence supports the view that conformational variations of PrP(Sc) encoded the biological properties of the various prion strains that have been isolated by transmission studies in experimental models. Infectious forms of human prion diseases played a pivotal role in the emergence of the prion concept and in the characterization of the very unconventional properties of prions. They provide a unique model to understand how prion strains are selected and propagate in humans. Here, we review and discuss how genetic factors interplay with strain properties and route of transmission to influence disease susceptibility, incubation period and phenotypic expression in the light of the kuru epidemics due to ritual endocannibalism, the various series iatrogenic diseases secondary to extractive growth hormone treatment or dura mater graft and the epidemics of variant Creutzfeldt-Jakob disease linked to dietary exposure to the agent of bovine spongiform encephalopathy.
authors: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Inserm, U 1127, CNRS UMR 7225, ICM, F-75013 Paris, France; AP-HP, Groupe hospitalier Pitié-Salpêtrière, Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob, F-75013 Paris, France; Centre National de Référence des Agents Transmissibles Non Conventionnels, F-75013 Paris, France. Electronic address: stephane.haik@upmc.fr.
authors: Stéphane
authors: S
authors: Haïk
authors: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Inserm, U 1127, CNRS UMR 7225, ICM, F-75013 Paris, France; AP-HP, Groupe hospitalier Pitié-Salpêtrière, Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob, F-75013 Paris, France; Centre National de Référence des Agents Transmissibles Non Conventionnels, F-75013 Paris, France.
authors: Jean-Philippe
authors: JP
authors: Brandel
mesh_terms: D000818:Animals; D002190:Cannibalism; D006801:Humans; D007049:Iatrogenic Disease; D017096:Prion Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology* / Q000635:transmission; D011328:Prions / Q000235:genetics* / Q000378:metabolism*; D015047:Zoonoses
chemical_list: D011328:Prions
keywords: Creutzfeldt-Jakob disease; Infectious forms; Kuru; Prion diseases; Prion strains