[Natural history of human transmissible subacute spongiform encephalopathies]

Transmissible spongiform subacute encephalopathies are rare fatal diseases which comprise in humans Creutzfeldt-Jakob disease (CJD), Kuru, Gerstmann Straüssler Scheinker, and Fatal Familial Insomnia (FFI). Their etiologic agents (Prions or TSA, for transmissible spongiform encephalopathy agents) are still unknown. TSA/prions resist all the physico-chemical procedures which are efficient against the other micro-organisms. These diseases are characterised by a long incubation period which may be as long as 40 years. Clinically, symptoms are only neurological, without any sign of immune response either in blood or cerebrospinal fluid. Neuropothalogy includes neuronal vacuolisation, neuronal death, spongiosis, gliosis with hyperastrocytosis. The biochemical hallmark is the post-translational accumulation of a host-encoded protein, the prion protein (PrP). In infected individuals, PrP accumulates under a proteinase K resistant isoform (PrP-res) which amino acid sequence does not differ from the normal isoform (PrP-c) PrP gene (PRNP) is located on chromosome 20 in humans, and is the major determinant of the susceptibility to TSA/prions. Several hypotheses have been raised to explain the uncommon biologic properties of these agents. The prion hypothesis postulates that the agent is only composed of proteins, mainly the PrP-res. Others support the presence of a host independent genetic information of which PrP could be the virulence factor.