title: Agents that cause transmissible subacute spongiform encephalopathies.
abstract: Transmissible spongiform encephalopathies (TSE) are characterised by a long incubation period which precedes clinical symptoms related to the degeneration of the central nervous system (CNS). The nature of their etiologic agents (TSA/prions) remains unknown, although there exists strong experimental data supporting the prion hypothesis. This hypothesis suggests a key role for the host derived protein (the prion protein, PrP) as the transmissible agent. In infected individuals, PrP accumulates proportionally to infectivity titre and resists proteinase K treatment (PrP-res). Iatrogenic Creutzfeldt-Jakob disease (CJD) cases have been described in humans after neurosurgery, treatment with pituitary derived hormones, and cornea and dura mater grafting. TSA-associated infectivity is dependent upon the nature of the organ in a given infected individual, though the CNS has the highest infectivity rate. In vitro, TSA/prions do not replicate easily: only cells of neuronal origin are susceptible, and the replication rate is very low. TSA/prions have unconventional properties; in particular, they resist to almost all the chemical and physical processes which inactivate conventional viruses. Only autoclaving at 134/136 degrees C for 1 h or treatment with either 1N NaOH or sodium hypochlorite (2% Cl) during 1 h at room temperature are considered to give inactivation that is compatible with public health criteria. In vivo, the distribution of infectivity is dependent upon strain and host, for a given inoculum injected by a given route. Although supported by numerous experimental data, the prion only hypothesis has not yet been convincingly demonstrated.
authors.affiliation: CEA, Service de Neurovirologie, DSV/DRM, Centre de Recherches du Service de Santé des Armées, Fontenay-aux-Roses, France.
authors.forename: D
authors.initials: D
authors.lastname: Dormont
mesh_terms: D006801:Humans; D017096:Prion Diseases / Q000209:etiology* / Q000635:transmission; D011328:Prions / Q000378:metabolism
chemical_list: D011328:Prions