Prions Flashcards
What makes prions different from classical pathogens?
Classical pathogens have nucleic acid genomes
Prions are proteinaceous infectious particles that lack nucleic acid (Stanley Prusiner’s ‘protein-only prion’ theory)
What are prions and what do they do?
They are small, proteinaceous particles
They form large vacuoles in the CNS, which causes motor disturbances
They are slow diseases; it takes between 1 and 35 years between infections and symptom onset
What are examples of common prion disease?
Scrapie in sheep BSE in cattle Chronic wasting disease in elk Kuru in humans Creutzfeld-Jakob disease (CJD) in humans
What is vCJD?
It is a variant of CJD which seems to have a much shorter incubation time. It’s the only variant where the disease is transmitted from cows to humans (or animals for that matter)
What is PrP?
It is a 30-35 kDa host-encoded glycoprotein that is expressed mainly on the surface of nerve cells
What is PrPc?
It is uninfective
It has an alpha-helical conformation
It is susceptible to proteases
What is PrPsc?
It is infective
It has a beta-sheet conformation
It is protease resistant, which causes it to accumulate
Explain the conversion of PrPc into PrPsc
Normal cells express PrPc at the cell membrane as linear proteins
Perps exists as a free globular glycoprotein, which can interact with PrPc
PrPc is released from the cell membrane and is converted into PrPsc
Cells produce more PrPc and the cycle is repeated
PrPsc accumulates as plaques, and is internalized by cells
How do prion diseases develop and transmit?
Mutations in codon 129 of PrPc in chromosome 20
Exposure to infective agent (more common)
What disease are caused by a mutation in codon 129 of PrPc in chromosome 20?
CJD and two other diseases: Gertsmann-Straussler-Scheinker syndrome and fatal familial insomnia
How does someone develop a prion disease through exposure to infective agents?
Contaminated food
Contaminated medical products (blood, transplants)
Contaminated surgical instruments (strong binding to metal surfaces)
Mother to fetus transmission (?)
From where do prion diseases shed?
Skin Feces Urine Milk Nasal secretions Saliva Placenta
How are prion diseases diagnosed and treated?
It is very difficult
There is not culturing or serology testing
There is no inflammation
A good source of PrPsc is tonsillar tissue
Treatment: none to date (there are experimental studies on rodents with polyanionic and tricyclic compounds)
