8 Prions

Question 1

Prions are host-derived glycoproteins. They acquire alternative conformations, and cause disease. Form insoluble beta-sheet rich amyloid fibrils, resistant to proteolysis. Lack nucleic acid genome, and resistant to all disinfection processes. They can be infectious

Can arise endogenously by mutation (and inherited) or exogenously acquired during medical procedures or ingestion of contaminated material.

What are examples of human prion disease?

Answer 1

CJD - sporadic, inherited, acquired (variant).

Fatal familial insomnia - sporadic, inherited

Kuru - sporadic, acquired

Gerstmann-straussler-scheinker - sporadic, inherited

Question 2

Prion diseases can cause large vacuoles in CNS - spongiform encephalopathy.

What are characteristics of a prion?

Answer 2

<100nm therefore filterable

lack of nucleic acid

extreme resistance to heat, disinfectants, irradiation. But susceptible to high concentrations sodium hydroxide

Slow replication - incubation can be up to 35 years. Can be more rapid in variant CJD

Cannot be cultured in vitro

Does not elicit immune or inflammatory response

Question 3

How are prion diseases transmitted iatrogenically?

Answer 3

Blood transfusion
Hormone extract - growth hormone
Transplants
Surgical instruments

Question 4

How does variant CJD occur?

Answer 4

Variant CJD thought to be acquired from eating contaminated brain/nervous tissue from cows with bovine spongiform encephalopathy (not from lean meat). Not digested, and transfers over gut border. Carried by lymphoid cells into neural tissues, then CNS.

Cows themselves became infected when scrapie (prion disease) crossed species from sheep.

Question 5

Difficult to diagnose prion disease, as can’t be cultured. Long incubation period, and cannot be diagnosed easily in early stages.

What is used for diagnosis??

Answer 5

MRI brain
CSF 14-3-3 protein
Tonsil biopsy - immunohistochemistry