Prions Flashcards
Prions are…
Infectious agent composed of a protein with an abnormal conformation
Prions cause
TSE - Transmissible Spongiform Encephalopathy
Human Prion Diseases (TSEs) Include:
Kuru Creutzfeldt-Jakob Disease (CJD) Variant CJD Gerstmann-Straussler-Scheinker (GSS) Syndrome Fatal familial insomnia Sporadic fatal Insomnia
Animal Prion Diseases (TSEs) Include:
Scrapie (Sheeps and goats)
Transmissible mink encephalopathy
Bovine spongiform encephalopathy (BSE(Mad Cow Disease))
Chronic Wasting Disease (mule, deer, elk)
Kuru
1950s, Fore people ofof Papua New Guinea, !% Incidence, Tremor, Muscular incapacity, dementia, death within 1 year
Differences compared to Classic Viruses
No Defined morphology Cannot be disinfected No Cytopathological effect No Immune response No Interferon production No Inflammatory Response
PrPC
Cellular Prion Protein
207 amino acid protein encoded by human chromosome 20
Found on Neurons, Lymphocytes, Follicular DCs, interacts and modulates some membrane proteins in brain: Copper shuttling, Pottasium channels, Neural cell adhesion molecule
PrPSC
Abnormal Post-translational converted Isoform of PrPC.
Contains more Beta Sheets
PrPC to PrPSC
Aggregation
Differences of PrPSC
multimeric Protease Resistant Forms Fibrils Exists outside Cell Long Turnover
Pathogenesis
- No cytopathologic effect
- long doubling time & incubation
- Cause vacuolation of neurons (Spongiform), Plaques, gliosis
- Cause loss of muscle control, shivering, tremors, dementia
- Lack of antigenicity
- Lack of inflammation
- Lack of immune response
Transmission
Infected Tissue
Inherited
Random Occurrence
Treatment
No Treatment (dont eat human brain)
Clinical Syndromes of CJD
Long incubation period (1-30 years) Rapid progression to death after onset of symptoms (~8 months) Loss of Muscle Control Shivering Myoclonic jerks and tremors (random jerks, experienced by everyone) Loss of coordination Rapidly progressive dementia DEATH
Diagnosis
No methods for detecting Prions No serologic response Based on clinical symptoms Confirmation by MRI Real confirmation at autopsy (amyloid plaques, spongiform vacuoles, Protein-misfolding cyclic assay)
