Question
Prions.
Answer
Prions: infectious, misfolded proteinaceous particles, devoid of any nucleic acid, causing disease by inducing the conformational conversion of the normal host cellular prion protein (PrP^C, predominantly alpha-helical) into an abnormal, disease-associated isoform (PrP^Sc, predominantly beta-sheet-rich), which is protease-resistant, aggregation-prone, and accumulates in neural tissue.
Diseases caused: collectively termed transmissible spongiform encephalopathies (TSEs) — in humans, Creutzfeldt-Jakob Disease (CJD) (sporadic, familial, iatrogenic, and variant forms), Kuru, Gerstmann-Sträussler-Scheinker syndrome, and Fatal Familial Insomnia; in animals, Bovine Spongiform Encephalopathy (“mad cow disease”) and Scrapie (in sheep).
Pathology: characterized by neuronal loss, spongiform (vacuolar) change, and astrogliosis, notably without any accompanying inflammatory response (distinguishing prion disease from conventional infectious encephalitis).
Key features: remarkably resistant to standard sterilization/disinfection methods (including standard autoclaving and formalin fixation), necessitating special decontamination protocols (e.g., prolonged autoclaving with sodium hydroxide pretreatment, or incineration of disposable instruments) for suspected/confirmed cases in surgical/laboratory settings.
Diagnosis: CSF RT-QuIC assay (a highly sensitive, specific test detecting seeding/conversion activity of abnormal prion protein), CSF 14-3-3 protein, characteristic EEG (periodic sharp-wave complexes) and MRI findings; definitive diagnosis requires brain biopsy/autopsy demonstrating spongiform change and PrP^Sc.
Treatment: no effective treatment currently exists; management is supportive, and the diseases are uniformly fatal.