II. SPONGIFORM
ENCEPHALOPATHIES (PRION DISEASES)
A.
INTRODUCTORY CONCEPTS; CHARACTERISTICS OF PRIONS
- 1. Human transmissible spongiform encephalopathies (including Creutzfeldt-Jakob
(C-J) disease and kuru) have been transmitted to primates and to other animals
through cell-free injections of infected brain tissue. Spongiform encephalopathies
occur in several mammalian species. Scrapie affects sheep, and bovine
spongiform encephalopathy occurs primarily in cows. Kuru, which affects
humans, is associated with cannibalism in New Guinea natives. C-J syndrome
and Gerstmann-Straussler-Schenker syndrome, which affect humans, appear
to occur through both genetic and infectious routes, as known for scrapie.
- The infectious agent has been characterized and is resistant to inactivation
by ultraviolet radiation, formalin, heat and enzymes which denature nucleic
acids. It can be inactivated (i.e. its infectivity destroyed) by proteases
and other treatments that denature proteins. The term "prion"
was used to describe this small proteinaceous infectious particle. Abnormal
forms of the prion protein (a ubiquitous protein of unknown function) cause
these neurodegenerative diseases. The disease occurs when the normal cellular
prion protein undergoes a conformational change to the abnormal form. This
may occur spontaneously at an extremely low rate or at a higher rate if
there is a defect in the gene. The agent can "replicate" when
the abnormal form crosses the path of the normal, cellular prion protein
and the abnormal prion induces the normal form to adopt a similar abnormal
form.