Prion disease - Basic science (Dr Wille) Flashcards

1
Q

What is the first prion disease that was described?

A

Scrapie

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Is scrapie transmissible to humans?

A

No. Only contagious to sheep and goats; forms holes in their brains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the 3 manifestations of human prion disease?

A
  • Sporaic: Creutzfeldt-Jakob disease (1920s)
  • Inherited: Germlines mutation in PRNP gene (usually dominant)
  • Infection: Transmitted via canibalism, medical procedures, consumption of infected fppd
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is most common of human prion disesae?

A

Sporadic (90%); familial (10%); infectious (1%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the death chances w/ prion disease?

A

1:5000

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is kuru?

A

Prion disease trasmitted via ritualistic cannibalism in Fore tribe; discovered by Dr. Carleton Gajdusek;

Slow disease (5-50 years incubation); now extinct

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is bovine spongiform encephalopathy?

A
  • Caused by feeding meat and bone meal to cattle (industrial cannibalism) –> mad cow’s disease
  • No contamination to pastures like scrapie
  • Three strains: classical; atypical and genetic
  • Classical is transmitted to humans
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the diff between sporadic CJD and variant CJD?

A

Sporadic affects elderly; variant affects younger

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How many people showed signs of abnormal PrP deposits?

A

Apenndixes showed 1:2000 in Great Britain; high prevalence

Tonsils and appendix are where prions show up first

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Where is chronic wasting disease found?

A

Deer, elk moos

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Does CWD transmit via tissue, feces, saliva, urine?

A

YES. It is the most infectious prion disease we know

Slide 17

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

TRUE or false: are caribou threatened?

A

Yes, but it has not been trasnmitted yet

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

TRUE or False: Cooking reduces infectivity substantially

A

False, only marginally

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe the overall human-human transmissions:

A
  • Kuru: very efficient, not a problem anymore
  • Iatrogenic CJD: very efficient, may be problem in UK
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the overall cattle-human transmissions:

A

BSE: Primary transmission relatively inefficient, incubation period uncertain; documented secondary transmirrion (eg blood transfusion)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe the overall sheep/goat-human transmissions:

A

Scrapie: no documented transmission, exposure suspected to be widespread.

17
Q

Describe the overall deer/elk/moose-human transmissions:

A

CWD: Well documented exposure in increasing numbers, but no transmission so far; transmisison to non-human primates have been recorded

18
Q

Is a prion a virus?

A

No

19
Q

Where do prions first show up?

A

Specialized population of immune cells in illeum; peyers patch; these cells sample content of gut and present antigens to immune cells on other side (trains antigens to not be allergic to food); however they are also** responsible to transport prions **

immune cells can get infected and spread prions

20
Q

How are prions taken up in the nervous sys?

A

Vagus nerve, mesenteric ganglion complex

21
Q

What is a prion?

A
  • Proteinacrous infectious particles
  • Pathogens
  • Composed of only protein
  • Devoid of nucleic acid
  • Coded by PRNP
  • Can be folded into an infectious form PrpSc
22
Q

Describe diff. between PrpC, PrpSc

A

PrpC: non infectious; cellular form of prion protein; PrpSc: infectious form, can be insoluble, resistant to proteolysis

23
Q

What is Prp 27-30?

A

N-terminal truncation of PrpSc, still infectious

24
Q

What is recPrp

A

recombinant, bacterially expressed prion protein, no post-translation moD.

not automatically infectious

25
Q

What dogmas did the prion hypothesis break?

A
  1. All infectious agents have DNA or RNA (virology dogma)
  2. Info flows from DNA to rna to proteins only (mol. bio dogma)
  3. Native structure of a protein only determiend by amino acid seq (Anfinsen’s dogma)
26
Q

What does GP1 do?

A

Anchors prion protein

27
Q

What are ZIPs?

A

Prion protein ancestor; first exon went through retrotransposon event and became PrP gene; part of the SLC39 family - they have Irt-like proteins, Zn2+ transporters

28
Q

Is Prnp found in lower vertebrates?

A

No

29
Q

TRUE or FALSE: prion disease occurs in non mammals

A

False

30
Q

Why is it hard to work w prion proteins?

A

aggregated; insoluble; infectious; hard to do x-ray crystallography and solution NMR

31
Q

What do we know about prpsc strucutre?

A

Contain alot of beta sheet

current strucutre is the cryo EM strucutre

32
Q

What is PIRIBS?

A

PARALLEL IN-REGISTER INTERMOLECULAR BETA-SHEET STRUCUTRE; shown to make up prion structures

Can also be four-rung beta solenoid strucutre

33
Q

What is the prion cloud hypothesis?

A

Diff. conformations in diff. parts of the brain would contribute to diff. disease (major vs. minor conformations)

34
Q

What is the refolding and seeding model for prion replication?

A

slide 48

35
Q

What are the issues with immunization in prp?

A
  1. Immunization w misfolded Prpsc would lead to disease
  2. Immunization w native Prpc could be unspecific or cause autoimmune; however it would reduce substrate conc. and delay disease
  3. Immunization w unspecific protein results in unspecific/autoimmune response
36
Q

What are the 3 most common genetic prion dieases?

A

P102L (GSS); D178N (FFI); E200K (fCJD)

37
Q
A