lecture 18- prions Flashcards
What are the differences between a virus and a prion?
Prions: no genetic info, protein only, no adaptive immunological response
viruses: contain gene info, DNA/RNA, protein, some with lipid coat, immunological response
what disease was involved with identifying prions?
scrapie
what does prion actually mean
proteinaceous infectious particle
why does UV kill viruses, but not prions?
UV interacts with DNA/genetic info- prions do not have nucleic acid
What is the protein-only hypothesis?
prions self-replicate without nucleic acid by converting a normal protein into a misfolded, infectious form
infectious agent is protein, versus nucleic acid
How do prions replicate?
cellular prion protein undergoes a conformational change to become disease prion protein (ex PrPc becomes PrPsc) –> misfolded protein is what accumulates
What are the different etiologies of prion diseases?
sporadic (most common), inherited, acquired
what is the most common etiology of prion disease in humans?
Sporadic Creutzfeldt-Jakob disease (CJD) (85-90% of all human cases)
examples of prion diseases?
mad cow, scrapie, kuru, chronic wasting disease, creutzfeldt-jakob disease
what do all prion diseases have in common? 6 things
Fatal
Transmissible/infectious
Spongiform neurodegeneration
Long incubation time
Short clinical phase
No treatment or prophylaxis available
What are the most important animal prion diseases?
scrapie (sheep and goats)
BSE (cattle)
CWD (elk and deer)
what changes are seen with classical scrapie
behavioural
Incoordination
Tremor
Ataxia
Pruritus
where are infectious prions found / shed with scrapie?
Prions found in urine, saliva, feces, milk
what is different about atypical scrapie?
Pruritus is uncommon (ataxia and incoordination is common), different /diffuse distribution in brain (not in opex)
found in more than 20 European countries, The Falkland Islands, USA, New Zealand,
Australia, Canada
What to do if you suspect a prion case – what material is needed for diagnosis?
mainly brain homogenates (obex region of brain stem), in some cases biopsies (ante mortem) rectoanal mucosa-associated lymphoid tissue
(RAMALT), retropharyngeal lymph node (CWD and scrapie)
must detect misfolded protein (PRPsc) (must detect protease resistant prion protein)
Which tests are used for diagnosis and what is detected?
immunoblot (western blot) - look for protease resistant prion protein
ELISA- detects PrP sc
immunohistochemistry/histopathology - antibody-based detection of PrPSc in tissue slices
Are prion diseases zoonotic?
YES
true or false: PrPc and PrPsc have a different amino acid sequence
what is the significance of this regarding antibody response?
false - it is the same
antibodies cannot differentiate cellular from scrapie
can you use PCR to detect prions?
noooooo same primary structure/ AA sequence
can you select against scrapie?
yes, you can select against classical scrapie BUT not atypical scrapie
still reduces scrapie though
what are clinical signs of classical BSE?
behaviour (Anxiety, Teeth grinding, Frequent nose licking, Tremors), sensory system (hypersensitive to touch, noise, light), locomotion (ataxia, hypermetria, cannot get up)
true or false- BSE is transmitted by contact (is contagious)
FALSE - BSE does not have prion shedding (stays in brain)
transmitted by ruminant-derived meat and bone meal (‘neo-cannibalism’)
when was the most recent case of classical BSE in alberta detected
feb 2015
what animal is resistant to BSE ???
dogs !
who is naturally susceptible to BSE
humans, cats, exotic ungulates, (and cattle obvi)
what are 3 significant differences with variant Creutzfeldt-Jakob disease (vCJD) versus sporadic Creutzfeldt-Jakob disease (sCJD)
what is the significant of CJD
- Median age at death: 28 years (versus 68)
- Clinical phase: 14 months (versus 6 months)
- Ataxia, psychiatric symptoms (versus dementia)
CJD is disease humans get from BSE
what types of BSE are there?
classical
H type atypical
L type atypical
what is significant about chronic wasting disease?
infects wild living and farmed animals
how is CWD transmitted
horizontal and vertical – oral infection
what are the clinical signs of CWD?
progressive weight loss
behavioral changes
depression and isolation
hypersalivation
teeth grinding
lack of coordination
difficulty swallowing
extreme thirst and urination
pneumonia
what is the most contagious prion disease?
chronic wasting disease
true or false: the camelid prion disease has a different molecular signature than BSE and scrapie
true
