Test 3 - Prions

Question 1

Human genetical prion disease includes… (3)

Answer 1

1. Fatal Familiar Insomnia
2. Gerstmann-Straussler Syndrome
3. Creutzelds-Jakob Disease

Question 2

Human non-genetic prion disease includes…

Answer 2

Kuru

Question 3

Prion is unique as an pathogen because it..

Answer 3

can cross species easily.

Question 4

Prion Discovery: First Step? Basis of the step? What is classified as originally?

Answer 4

Viral v Bacterial: Filter. Size. If bacterial, in retentate. If viral, in flow-through. Prion was in FT.

Question 5

Prion Discovery: Second Step? Basis of the step? What was it classified as?

Answer 5

DNA or RNA: Treating with DNA or RNA. Basis that treating with same nucleic acid will cause loss of infectivity. (If DNA, treating with DNA –> Loss of infectivity. IF RNA, treating with RNA–> loss of infectivity. Classified as neither.

Question 6

Prion Discovery: Third Step? Why did they chose to do this? Theoretical basis of the step? What was it classified as?

Answer 6

Radiation Bombardment, because 2nd step thought not to work because genetic material is too tightly bound. If DNA/RNA, radiation will cause loss of infectivity. Classified as NOT a nucleic acid!!!

Question 7

Prion Discovery: The Last Step? Basis of the step? What was it classified as?

Answer 7

Protease Treatment. Hypothesis that if protein, prion will lose infectivity. Infectious agent is protein.

Question 8

What causes scabies?

Answer 8

PrP^(sc)

Question 9

What are the characteristics of PrPsc? What is it involved in?

Answer 9

PrPsc is very stable and binds to Ca2+. May be involved in stem cells, long term memory, or neuronal repair.

Question 10

The similarities between PrPsc and PrPc is…

Answer 10

1’ Structure – Same AA sequence.

Question 11

The difference between PrPsc and PrPc is…

Answer 11

2’ Structure – Different Folding. PrPsc is mostly ß sheets, while PrPc is mostly α helixes.

Question 12

α helixes makes __1__ (soluble/insoluble) and (protease sensitive/resistant)

Answer 12

α helixes makes PrPc soluble and protease sensitive

Question 13

ß sheets makes__1__ (soluble/insoluble) and (protease sensitive/resistant). Why is it resistant/sensitive?

Answer 13

ß sheets makes PrPsc insoluble and protease resistant. Resistant because ++stability. (Hence High ∆G++)

Question 14

Prion Disease grows in a … pattern.

Answer 14

Exponential

Question 15

Prion disease manifests itself in … in autopsied samples

Answer 15

long polymers of PrPsc

Question 16

What is the Heterodimer Model of Prion Disease? What does it explain? What doesn’t it explain?

Answer 16

PrPc and PrPsc bind to create a Heterodimer. AND THEN, PrPsc acts as an enzyme to convert PrPc –> PrPsc. This explains exponential growth (due to + loop). This does not explain polymers or the fact that monomers of PrPsc are never seen in autopsy.

Question 17

What is the Polymerization Model of Prion Disease? What does it explain? What doesn’t it explain?

Answer 17

PrPsc reacts with PrPc and makes PrPc–>PrPsc before they bind together to form polymers. It explains polymers but does not explain why the growth is exponential (this model predicts linear growth).

Question 18

What is the ADDENDUM TO Polymerization Model of Prion Disease? What does it explain? What doesn’t it explain?

Answer 18

Polymers of PrPsc can break off to create another strand of polymer. It explains exponential growth, but cannot explain how the polymers break up in the first place.

Question 19

Infection: Prion disease has a short incubation period (T/F)

Answer 19

F

Question 20

Infection: What are the 3 forms of prion disease?

Answer 20

1. Acquired Prion Disease.
2. Sporadic PD
3. Familiar PD

Question 21

Infection: Acquired PD is from… (examples?)

Answer 21

coming into contact with infectious agent, like corneal transplant or tainted meat.

Question 22

Infection: Sporadic PD is from…

Answer 22

Random conversion of PrPc to PrPsc, which is VERY rare due to ∆G++.

Question 23

Infection: Familiar PD is from…

Answer 23

Mutation in PRNP Gene, which codes for PrPc. This mutation makes PrPc–>PrPsc more likely by lowering ∆G++. Families have a predisposition to acquiring prion disease because of this.

Question 24

What was the difference of onset of Prion Disease in PrPc-Knockout Mice and mice with overexpressed PrPc?

Answer 24

Immunity v. rapid onset.

Question 25

What are the two phases of infection for PD?

Answer 25

1. Colonization of Immune System

2. Transmission into Nervous System.

Question 26

In the first step of PD infection, PrPsc appears in… (ex), especially…

Answer 26

the immune system (ex. lymph node, tonsill, spleen, appendix.), especially B cells.

Question 27

Is the immune system necessary and sufficient for PrPsc infection? Why or why not? Conclusion from this?

Answer 27

Not quite. If injected intramuscularly into mice without immune system, PrPsc does not cause infection. However, if injected directly into the brain, the mice still got the disease. This means that immune system is a processing center BUT isn’t necessary.

Question 28

How does the PrPsc from immune system go into the brain?

Answer 28

No idea.

Question 29

In the brain, PrPsc forms…

Answer 29

sponiform phenotype (spongy brain).

Question 30

Detection of PrPsc is difficult because (3)…

Answer 30

1. Most detection tests with PCR, which requires nucleic acid.
2. Even if an antibody existed, PrPsc and PrPc has the same sequence.
3. Urine and blood has very low levels of PrPc.

Question 31

Treatment of PrPsc is aimed toward… What is a recent finding related to this?

Answer 31

Slowing down the exponential growth. Antibody that can cross blood-brain barrier and prevent PRPsc from colonizing the brain.

Question 32

One way to make PrPsc-immune domestic animals is to…

Answer 32

Make cows genetically modified to not have PrPc.