Lec 15: Prions

Question 1

the causative agents (Prions) are =

Answer 1

protein molecules from within the HOST cells

Question 2

no _______ ____ has been found associated with prions.

Answer 2

nucleic acid

Question 3

essentially, prions are

Answer 3

infectious proteins.

Question 4

Discovery of prion infectious properties

Answer 4

1. ) Mouse prion protein was produced in recombinant bacterial cells and polymerized into fibrils
2. ) Injected into the brains of mice
3. ) The mice subsequently developed signs of a TSE and
4. ) Extracts of their brains transmitted the disease to other mice

Question 5

The prion diseases are characterized by

Answer 5

very long incubation periods, measured in years.

Question 6

The incubation period of an infectious disease =

Answer 6

the time that elapses between the infectious agent entering the host and the first appearance of signs and symptoms of the disease.

Question 7

Signs of prion disease =

Answer 7

dementia and loss of coordination

the patient gradually deteriorates, and death is inevitable.

Question 8

The prion diseases are known as:

Answer 8

transmissible spongiform encephalopathies (TSEs)

Question 9

• encephalopathy =
• spongiform =
• transmissible =

Answer 9

• encephalopathy = disease of the brain
• spongiform = the development of holes in the brain, making it appear like a sponge
• transmissible = the fact that the causative agent is infectious. It can be transmitted to members of the same species, and sometimes to other species.

Question 10

Prions appear as

Answer 10

misfolded forms of normal cell proteins

Question 11

Versions of the normal protein have been found…
in humans it is…
The role of the protein is…

Answer 11

…in mammals, birds and reptiles
…encoded by the Prnp gene
…not yet clear

Question 12

PrnP-null mice show

Answer 12

no physiological or developmental differences.

Question 13

Prions cycle between:

Answer 13

endosomes and the cell surface

Question 14

Prions are found on many cell types, but especially on:

Answer 14

cells of the central nervous system

Question 15

the protein exists as 3 Glycoforms: (sugars attached)

Answer 15

1. ) Unglycosylated (none)
2. ) Monoglycosylated (one)
3. ) Diglycoslyated (two)

Question 16

The conformation of much of the normal protein is…

But, when the protein misfolds…

Answer 16

…α helix.

…there is a decrease in α helix structure and an increase in β sheet

Question 17

Prion infectivity is remarkably

Answer 17

heat resistant and some infectivity can survive autoclaving for prolonged periods (ex: cooking won’t kill prions)

Question 18

A small subpopulation of the infective material (prions) has

Answer 18

a higher level of resistance to inactivation.

Question 19

Prion infectivity is also very resistant to

Answer 19

inactivation by irradiation and by some chemicals that inactivate virus infectivity.

Question 20

Treatments that are used to inactivate prion infectivity include

Answer 20

exposure to 2.5–5 per cent sodium hypochlorite solution or 1 M NaOH for 1–2 hours.

Question 21

3 ways to get Prion disease:

Answer 21

1. ) Some prion disease cases arise spontaneously
2. ) Some are inherited
3. ) Some are acquired as a result of a TSE agent entering the body (Agents serve as trigger to trick normal proteins to misfold like them)

Question 22

Prion replication takes place slowly, but…

Answer 22

…because the misfolded protein is not degraded, concentrations gradually build up

Question 23

The prion proteins form

Answer 23

insoluble aggregates, often visible as ‘plaques’ in sections of central nervous tissue.

Question 24

The accumulation of these aggregates (plaques) is thought to lead to:

Answer 24

dysfunction and death of neurons, leading to the development of the holes in the brain.

Question 25

Prion diseases in humans =

Answer 25

vCJD is a relatively new disease.

Question 26

because vCJD’s appearance coincided with…

laboratory studies demonstrated that…

Answer 26

…the BSE (Bovine Spongiform Encephalopathy) outbreak in the UK it was suggested that it had resulted from humans ingesting the BSE prion.
…the BSE prion and the vCJD prion have identical molecular characteristics, and that they induce identical responses in inoculated mice.

Question 27

the most common human prion disease

Answer 27

Sporadic CJD

Question 28

Kuru and vCJD are acquired by

Answer 28

ingesting prions

Question 29

In the case of Kuru the source of the prions was…

Answer 29

human brain tissue.

This disease used to occur in areas of New Guinea where it was the custom to eat tissue from relatives who had died.

Question 30

The efficiency of prion transmission depends on:

Whats also important?

Answer 30

the route by which the prion molecules enter the body
(injection into brain = more efficient than ingestion)

Dose is also important

Question 31

Many attempts to transmit TSE agents to

Answer 31

distantly related species have been reported as difficult.

Question 32

to prevent prion transmission, 1.) they banned the consumption of…
2.) testing of…

Answer 32

1. ) …animal brain, spinal cord and mechanically recovered meat from the spine.
2. ) …cattle and meat for the BSE prion using serological methods

Question 33

The Protein-Only Hypothesis:

Answer 33

1. ) introduction of the misfolded protein into the body of a new host initiates the misfolding of protein molecules in that host.
2. ) There remain many controversies and there is still much to be learned about the TSEs and their causative agents

Question 34

Progress in prion research is slow as a result of

Answer 34

the long incubation periods of the diseases.

Question 35

Prions act like…

but unlike viruses or bacteria…

Answer 35

…an infection

…they have no DNA

Question 36

Developing prion cure strategies: (3)

Answer 36

Small molecules
Antibodies
Gene silencing