Unit 8 - Prions Flashcards
What are prions?
Protineacous infectious particle that lacks nucleic acid
How are prions different from classical pathogens?
They have nucleic acid genomes, where prions lack nucleic acid
Give an example of a disease caused by prions in cattle
mad cow disease (bovine spongiform encephalopathy)
Give an example of a disease caused by prions in sheep
Scrapie
Give an example of a disease caused by prions in elk
Chronic wasting disease
Give an example of a disease caused by prions in humans
Kuru, Creutzfeldt-Jakob disease
Describe the pathology of prions
Large vacuoles in CNS, motor disturbances
Prions cause ____ disease
slow
_____ years between infection and symptoms
1-35
______ kDA host-encoded glycoprotein
30-35
PrP stands for?
Prion Protein
Normal cells express PrPc at the ____ _______ as linear proteins
cell membrane
PrPSc exists as a _____ ______ _________
free globular glycoprotein
PrPSc can interact with ____
PrPc
PrPc is released from the ___ _______
cell membrane
PrPc is released from the cell membrane and is converted into ____
PrPSc
Cells then produce more ____ and the cycle is repeated
PrPc
PrPSc accumulates as ____ and is internalized by cells
plaques
What is the misfolded protein in TSE?
PrPSc
What is the misfolded protein in AA amyloidosis?
SAA
What is the misfolded protein in Alzheimers; cerebral B-amyloidosis?
AB
What is the misfolded protein in Parkinsons’?
alpha-synuclein (Lewy bodies)
What is the misfolded protein in Alzheimer’s; tauopathies?
Tau
What is the misfolded protein in ALS?
SOD 1
What is the misfolded protein in Huntington’s?
Huntington, polyQ expansions
In what 2 ways is there development and transmission of prion disease?
1) Mutations in codon 129 of PrPc in chromosome 20
2) Exposure to infective agent (more common)
Describe “Mutations in codon 129 of PrPc in chromosome 20”
-CJD and two other human diseases: Gertsmann-Straussler-Scheinker syndrome and fatal familial insomnia
Describe “Exposure to infective agent (more common)”
- Contaminated food (eating infected cow meat uncooked)
- Contaminated medical products (blood, transplants)
- Contaminated surgical instruments (strong binding to metal surfaces)
- Mother-fetus transmission? (Animals can for sure have mother-fetus transmission, there has only been one recorded case in humans of mother-fetus transmission)
How are prions shed?
- skin
- feces
- urine
- milk
- nasal secretions
- saliva
- placenta (still an investigated theory)
How can scrapie in sheep/goats be spread to humans?
Not spread directly!
- spreads to cattle first
- then a few cases have resulted in CJD in humans
How is kuru in humans spread?
cannibalism
What causes conversion of protein into the pathogenic form?
Mutations at amino acid residue 129 of the prion protein.
Describe diagnosis and treatment of prion infections
- Difficult
- No culturing, serology
- No inflammation
- Tonsillar tissue, good source of PrPSc
- No treatment to date right now, experimental studies in rodents, polyanionic and tricyclic compounds
*Not a virus, not a bacterium, not a fungi - cannot culture and study these
Give a brief summary of prions
- Unusual infectious agents
- Host-derived glycoproteins, lack nucleic acid genome
- Resistant to disinfection procedures
- Transmission: Ingestion or Latrogenic
List & Define the two types of transmission of prions
1) Ingestion: eating infected foods
2) Latrogenic: infection from medical procedures
