Prions Flashcards
(24 cards)
What is a prion?
An infectious protein which can be transmitted the same as viruses etc.
What is an example of a prion-based disease?
BSE in cattle (target species) transmitted by ingestion of contaminated meat
What are the first prion to be isolated?
Scrapie in infected sheep in 1980, led to the discovery that the protein identified with the PrP gene (expressed in the brain)
What are the 3 forms of prion-associated disease in humans?
1) Familial
2) Sporadic
3) Transmissible
What are the 2 types of prions?
1) Prp-sen - non-disease causing, normal variant
2) Prp-res - disease causing, atypical variant
What is the difference between ‘sen’ and ‘res’?
The folding is different
‘sen’ is sensitive to biological degradation, ‘res’ is resistant so accumulates as it can’t be broken down
What is the current theory of Prp-sen’s role in the body?
They are involved in communication between nerve cells (in sleep patterns and in cell death)
Do prions have genetic material?
Can they replicate within the body?
No.
There is evidence that they can replicate in the body.
How does Prp-res accumulate in the body?
Upon contact with the ‘sen’ isoform, ‘res’ isoform of the protein converts ‘sen’ into ‘res’
Can explain why disease leads to progressive neurological degeneration - more proteins converted across different body sites
How do prions link to progressive nuerological disease?
Prions stack into long chains - amyloid fibres (toxic to nerve cells)
Astrocytes move through brain and digest dead nerve cells, leaving gaps in the tissue but amyloid fibres are untouched
How does BSE affect cows?
Affects the brain and spinal cord
During the incubation period (4-6years from infection until symptoms show), there is no way to tell that a cow has BSE.
Currently no treatment/vaccine
What is transmissible Spongiform Encephalitis (TSE)?
Infectious prion can be transmitted between animals or to different species (cause ‘sponge-like’ tissue in the brain)
What are the 2 types of scrapie in sheep?
1) Typical (affects 2-5yr sheep) transmitted via colostrum/milk - associated to areas where animals have given birth
2) Atypical (affects >5yr), may be less contagious but not fully understood why
What are some of of the symptoms of scrapie?
Repeatedly rubbing head/body against fence, posts/hay
Nibbling feet/legs in an agitated way
Have excessive wool loss/skin damage
Will eventually kill any animals that are infected
What is the impact of scrapie?
Herds are required to be slaughtered - natural affects economic viability of farms
Affects national exports and reputation for food and animal health.
What is Creutzfeldt-Jakob disease (CJD)?
Neurodegenerative disease in humans - similar symptoms to BSE.
Deterioration rapidly progresses, is always fatal within 1 year of contracting
85% occurs as a sporadiac disease with no recognisable pattern of transmission
5% develop CJD due to inherited mutations
What are some of the diagnostics for CJD?
Presence of 14-3-3 protein in cerebrospinal fluid and/or typical EEG pattern
What is a confirmatory diagnosis for CJD?
Neuropathologic and/or immunodiagnostic testing of brain tissue obtained at biopsy/autopsy
Is there a treatment for CJD?
No. Care is supportive only
How does CJD present?
Rapid, progressive dementia and cerebellum dysfunction, neurological abnormalities
Where does polymorphism occur for CJD?
In the 129 codon on the human prion gene (valine/methionine)
What is variant CJD?
vCJD is found through consumption of animal produce containing prions - e.g. BSE
What are the features of vCJD?
Psychiatric and sensory problems at onset with dementia only developing in final stages
All patients presenting vCJD are homozygous for methionine at codon 129 in prion gene
What is Gerstmann-Straussler-Scheinker syndrome (GSS)?
Rare inherited autosomal dominant mutation/insertion of prion on chromosome 20
Affects mostly middle-aged persons
Linked to codon 102 proline->leucine mutation
