Unit 8 - Prions

Question 1

What are prions?

Answer 1

Protineacous infectious particle that lacks nucleic acid

Question 2

How are prions different from classical pathogens?

Answer 2

They have nucleic acid genomes, where prions lack nucleic acid

Question 3

Give an example of a disease caused by prions in cattle

Answer 3

mad cow disease (bovine spongiform encephalopathy)

Question 4

Give an example of a disease caused by prions in sheep

Answer 4

Scrapie

Question 5

Give an example of a disease caused by prions in elk

Answer 5

Chronic wasting disease

Question 6

Give an example of a disease caused by prions in humans

Answer 6

Kuru, Creutzfeldt-Jakob disease

Question 7

Describe the pathology of prions

Answer 7

Large vacuoles in CNS, motor disturbances

Question 8

Prions cause ____ disease

Answer 8

slow

Question 9

_____ years between infection and symptoms

Answer 9

1-35

Question 10

______ kDA host-encoded glycoprotein

Answer 10

30-35

Question 11

PrP stands for?

Answer 11

Prion Protein

Question 12

Normal cells express PrPc at the ____ _______ as linear proteins

Answer 12

cell membrane

Question 13

PrPSc exists as a _____ ______ _________

Answer 13

free globular glycoprotein

Question 14

PrPSc can interact with ____

Answer 14

PrPc

Question 15

PrPc is released from the ___ _______

Answer 15

cell membrane

Question 16

PrPc is released from the cell membrane and is converted into ____

Answer 16

PrPSc

Question 17

Cells then produce more ____ and the cycle is repeated

Answer 17

PrPc

Question 18

PrPSc accumulates as ____ and is internalized by cells

Answer 18

plaques

Question 19

What is the misfolded protein in TSE?

Answer 19

PrPSc

Question 20

What is the misfolded protein in AA amyloidosis?

Answer 20

SAA

Question 21

What is the misfolded protein in Alzheimers; cerebral B-amyloidosis?

Answer 21

AB

Question 22

What is the misfolded protein in Parkinsons’?

Answer 22

alpha-synuclein (Lewy bodies)

Question 23

What is the misfolded protein in Alzheimer’s; tauopathies?

Answer 23

Tau

Question 24

What is the misfolded protein in ALS?

Answer 24

SOD 1

Question 25

What is the misfolded protein in Huntington's?

Answer 25

Huntington, polyQ expansions

Question 26

In what 2 ways is there development and transmission of prion disease?

Answer 26

1) Mutations in codon 129 of PrPc in chromosome 20 | 2) Exposure to infective agent (more common)

Question 27

Describe "Mutations in codon 129 of PrPc in chromosome 20"

Answer 27

-CJD and two other human diseases: Gertsmann-Straussler-Scheinker syndrome and fatal familial insomnia

Question 28

Describe "Exposure to infective agent (more common)"

Answer 28

- Contaminated food (eating infected cow meat uncooked) - Contaminated medical products (blood, transplants) - Contaminated surgical instruments (strong binding to metal surfaces) - Mother-fetus transmission? (Animals can for sure have mother-fetus transmission, there has only been one recorded case in humans of mother-fetus transmission)

Question 29

How are prions shed?

Answer 29

- skin - feces - urine - milk - nasal secretions - saliva - placenta (still an investigated theory)

Question 30

How can scrapie in sheep/goats be spread to humans?

Answer 30

Not spread directly! - spreads to cattle first - then a few cases have resulted in CJD in humans

Question 31

How is kuru in humans spread?

Answer 31

cannibalism

Question 32

What causes conversion of protein into the pathogenic form?

Answer 32

Mutations at amino acid residue 129 of the prion protein.

Question 33

Describe diagnosis and treatment of prion infections

Answer 33

- Difficult - No culturing, serology - No inflammation - Tonsillar tissue, good source of PrPSc - No treatment to date right now, experimental studies in rodents, polyanionic and tricyclic compounds *Not a virus, not a bacterium, not a fungi - cannot culture and study these

Question 34

Give a brief summary of prions

Answer 34

- Unusual infectious agents - Host-derived glycoproteins, lack nucleic acid genome - Resistant to disinfection procedures - Transmission: Ingestion or Latrogenic

Question 35

List & Define the two types of transmission of prions

Answer 35

1) Ingestion: eating infected foods | 2) Latrogenic: infection from medical procedures