Prions and Prion Diseases Flashcards
What is a prion? What is their structure like?
pretentious infectious particle
200-250 amino acids twisted into 3 telephone cord-like coils known as helices, with a tail of more amino acids
Who proposed the idea of prions?
Stanley Pruisner - wanted to purify the “virus” causing scrapie
What is the great debate about prions?
how can a protein devoid of nucleic acid replicate and cause disease?
What are prions causing disease (encephalopathy) considered?
modified forms of the host-encoded glycoprotein PrPc into PrPSc
- PrPSc has the same amino acids, but a different shape
What 5 characteristics of prions make treatment difficult?
- PrPSc is resistant to any form of digestion (enzymes, biological decomposition)
- antibiotics cannot cure disease caused by prions
- not typical of prokaryotic for eukaryotic organisms
- non immunogens and do not induce an immune response
- resistant to high temperatures and disinfectants
Chain reaction conversion of PrPc to PrPSc:
What is PrPc and where is it usually found? What is its function?
small, glycosylated protein associated with brain cell membranes (NO NUCELIC ACIDS)
protect neurons from oxidative stress
- PrPc 0/0 knock out mice and cattle are resistant to prion infections, but are more susceptible to seizures
Geographical distribution of Bovine Spongiform Encephalopathy:
Virus vs Prion:
What are 4 common human prion diseases? Animal?
- Creuzfeldt and Jacob Disease
- Gerstmann-Strasussler
- Fatal Familial Insomnia
- Kuru
- Scrapie (goats, sheep)
- Transmissible mink encephalopathy
- Bovine Spongiform Enecphalopathy (mad cow disease)
- chronic wasting disease (mule, deer, elk)
How do prions spread? Where will they be concentrated?
feeding cattle animal byproducts, like meat and bone meals that has infected prion
brain and spinal cord
Can a prion-infected cow’s meat still be consumed?
yes - no evidence that prions are concentrated in the muscle mass of cattle; as long as there is no contact with brain and spinal cord during slaughter process
BSE infection cycle:
What is the most common way that cattle become infected with prion disease?
infected sheep die and their brains and other byproducts infected with scrapie are used to feed cattle with meat and bone meal (offal)
What are the 4 steps of prion pathogenesis in cows?
- cow eats offal of infected sheep
- prions are taken up from the gut and transported along nerve fibers to the brain stem
- prions accumulate and convert normal prion proteins into PrPSc
- years later, BSE results when a suffiient number of nerve cells have become damaged, affecting the behavior in cows and causes death
What is the general 5 steps of prions converting PrPc into PrPSc?
- α-helix converts into β-sheet
- prion acts as a template
- triggers chain reaction
- amyloid fiber production
- plaque formation
What is the typical manifestation of Scrapie? What are 3 additional clinical signs in sheep?
itching sensation
- excessive lick smacking
- altered gait
- convulsive collapse
What are 4 common histological findings on BSE-infected brain tissue?
- vacuolation of neurons and neuronal ground substance in cerebella/cortex
- perivascular fibrils of amyloid in which PrPSc can be demonstrated by immunostaining and Congo Red birefringence
- astrocyte infiltration
- spongiform gray matter
BSE, brain damage:
A = spongiform change in neurons
B = spongiform change and astrocytic hypertrophy and hyperplasia
BSE diagnosis:
