Chapter 9

Question 1

What are prions?

Answer 1

An infectious host-derived glycoprotein composed purely of protein (proteinaceous), lacking nucleic acid.
Common in humans and animals. Species specific (except for vCJD)
Resistant to heat, disinfectants and irradiation.

Question 2

What diseases do prions cause?

Answer 2

Scrapie (sheep), BSE (cattle), Chronic wasting disease (elk) and Kuru or Creutzfeldt-Jakob disease (humans)

Question 3

What is the pathology of prions?

Answer 3

Large vacuoles in the CNS (spongy brain), causing motor disturbances
Neurodegenerative disease

Question 4

What is the speed of vCJD?

Answer 4

1-35 years between infection and symptoms

Question 5

What is vCJD?

Answer 5

Variant of Creutzfeldt-Jakob disease. A prion that jumped from animals to humans. Only interspecies prion.

Question 6

What is the cause behind prions?

Answer 6

PrP, a host encoded glycoprotein expressed mainly on the surface of nerve cells.
Two types

Question 7

What is PrPc?

Answer 7

An uninfective glycoprotein with alpha-helical conformation. Susceptible to protease.
Exist at cell membrane as linear proteins.

Question 8

What is PrPsc?

Answer 8

An infective glycoprotein with beta-sheet conformation. Protease resistant, causing accumulation.
Exist as a free globular glycoprotein, which can interact with PrPc.

Question 9

How do our good prion proteins become bad ones?

Answer 9

PrPsc interacts with and releases PrPc and from the membrane. It is converted to PrPsc. The cells produce more PrPc and the cycle is repeated. PrPsc accumulates as plaques and is internalized by cells.

Question 10

What diseases are similar to prion diseases?

Answer 10

Alzhemiers, ALS and Huntingtons

Question 11

What diseases can mutation in codon 129 of PrPc in chromosome 20 (spontaneous) cause?

Answer 11

CJD, Gertsmann-Straussler-Scheinker syndrome and fatal familial insomnia

Question 12

What infective agents (iaterogenic) can cause prion diseases?

Answer 12

Food (beef, cannibalism), medical products (blood, transplants), surgical instruments (strong binding to metal surfaces), possibly mother to fetus

Question 13

How can prions be shed?

Answer 13

Skin, feces, urine, milk, nasal secretions, saliva and placenta

Question 14

Why do we believe that many people are genetically resistant to prion diseases?

Answer 14

They are shed so many ways and easily spread but it hasn’t infected as many people as it should have. Selection has already happened

Question 15

Which prion crossed the species boundary?

Answer 15

BSE crossed from cattle to human to become vCJD.

Question 16

Why are prion diseases difficult to diagnose before symptoms arise?

Answer 16

No culturing, serology. No inflammation.

Question 17

How could we potentially look for prions?

Answer 17

Design antibodies against the beta-sheet or alpha helix form and look for antigen-antibody interactions.

Question 18

Where can you get a good prion sample from?

Answer 18

From the tonsillar tissue.

Question 19

What is the treatment for prions?

Answer 19

Currently only experimental in rodents using polyanionic and tricyclic compounds