Prions

Question 1

Morphology

Answer 1

• pure protein: 30.000 Da (253 aminoacid)

* the infectious particle does not contain nucleic acid

Question 2

Resistance

Answer 2

extremely high
• 136-138 °C, 20 min
• 8% NaOH, 3% formaldehyde (10 × more concentrated than usual)
• lipid solvents reduce heat resistance

Question 3

Biological properties

Answer 3

cellular prion protein (PrPc)
•normal component of the neurons (cytoskeleton, messenger)
•coded on the 20th chromosome (human)

infectious prion protein (PrPsc)
•PrPc and PrPsc differ in three amino acids in humans •isoform: α-helix → β-sheet
•resistant to proteases – accumulation in neurons
• host spectrum ?

in vitro possible bypass → in vivo indirect proves

Question 4

Antigenic properties

Answer 4

not antigenic – recognized as own

Question 5

Diagnosis

Answer 5

• clinical signs
• histopathology: vacuolization of neurons, amyloid plaques
• clinical signs
• histopathology: vacuolization of neurons, amyloid plaques

Question 6

What is a prion?

Answer 6

prion – protein of infectious nature, proteinaceous infectious particle

Question 7

Pathogenesis

Answer 7

• intestine → spleen, lymph nodes (6 months) → nerves (1mm/day)
• reach the CNS – modulator proteins: induce neurons to produce PrPsc
→ intracellular accumulation, aggregation, polymerization •amyloid plaques (3-4 years) – neuron degeneration → spongiform encephalopathy

Clinical signs: progressive CNS signs, behaviour changes → slowly developing, non-curable lethal disease

Question 8

Transmissible spongiform encephalopathies (TSEs)

Answer 8

Scrapie (known since the XVIIIth. century)
•sheep: incoordination, swaying, itching

Bovine spongiform encephalopathy (BSE), (since 1985)
•scrapie modification (?)
•behavior changes, „mad cow syndrome”

Feline spongiform encephalopathy (FSE)
•BSE modification (?)

Human: progressive dementia
• Creutzfeld-Jakob disease (CJD) – familial, sporadic, iatrogenic • variant Creutzfeld-Jakob disease (vCJD) – BSE origin?
• Gerstmann-Srtäussler-Scheinker syndrome (GSS)
• Kuru – ritual cannibalism
• Fatal familial insomnia

Question 9

Human: progressive dementia

Answer 9

• Creutzfeld-Jakob disease (CJD) – familial, sporadic, iatrogenic, shows sign at +40 years old
• variant Creutzfeld-Jakob disease (vCJD) – BSE origin? Shows signs at already 20 years old
• Gerstmann-Srtäussler-Scheinker syndrome (GSS)
• Kuru – ritual cannibalism
• Fatal familial insomnia

Question 10

Scrapie

Answer 10

•sheep: incoordination, swaying, itching - rubs body to the environment, loss of wool.

Question 11

What does iatrogenic mean?

Answer 11

Can be introduced during surgery

Question 12

What is Fatal familial insomnia?

Answer 12

A inherited disease –> modification in the genome.