Prions

Question 1

Insoluble aggregates of a specific protein fragment, high in β-sheet

Answer 1

Amyloid deposits

Question 2

What is the characteristic histopathology of prions in the brain?

Answer 2

1. ) Amyloid depositis

2. ) Vacuolar degeneration of tissue

Question 3

The vacuolar degeneration of tissue is a subacute or transmissible

Answer 3

Spongiform encephalopathy

Question 4

Classified as “slow virus” diseases. Sometimes take over 20 years to develop

Answer 4

Prion diseases

Question 5

There is no inflammation in damaged tissue and no immune response in a

Answer 5

Prion disease

Question 6

A human disease that can be transmitted by transplantation of tissue from an infected individual, or by use of contaminated medical instruments

Answer 6

Creutzfeldt-Jakob disease (CJD)

Question 7

Prion disease of the Fore people of the highlands of Papua New Guinea, was transmitted by the ritual consumption, by family members, of brain tissue from deceased relatives

Answer 7

Kuru

Question 8

A disease of sheep, named for the behavior of diseased animals, which scrape themselves against walls or trees. This is the best-studied form of prion disease

Answer 8

Scrapie

Question 9

The recent prion epidemic among cattle in new england is termed

Answer 9

Bovine spongiform encephalopathy (Mad Cow Disease)

Question 10

Transmission is by consumption of meat from infected animals, or of livestock feed derived from animal carcasses

Answer 10

Mad cow disease

Question 11

Human mad cow disease acquired from contaminated beef is termed

Answer 11

Variant CJD (vCJD)

Question 12

Believed to transport infections material from the digestive tract to brain, with amplification in secondary lymphoid organs

Answer 12

Macrophages

Question 13

CJD, Kuru, and Scrapie are all forms of prion disease acquired from

Answer 13

Infection

Question 14

What are the three prion diseases that are acquired from inheritance?

-All autosomal dominant

Answer 14

Gerstmann-Straussler-Scheinker (GSS) syndrome, Familial fatal insomnia (FFI), and Inherited Creutzfeldt-Jakob disease

Question 15

This is the common (85%) form of CJD. The incidence is about one case per million persons per year, in all populations. Mean age of onset is about 65 years

Answer 15

Spontaneous prion disease

Question 16

No bacterium, virus, fungus, or protozoan which produces prion disease has ever been cultured from infected tissue or visualized by light or

Answer 16

Electron microscopy

Question 17

Are highly stable

Answer 17

Prion diseases

Question 18

Contaminated material should be incinerated if possible. Otherwise the recommended procedure is a 1 hour soak in

Answer 18

1N NaOH

Question 19

Purified preparations of infectious material contain a single protein with molecular weight 27-30 kd. This protein forms the

Answer 19

Amyloids in the brain

Question 20

Recent experiments show that the most infectious fractions of brain tissue contain not the large amyloid aggregates but oligomers of

Answer 20

10-20 PrP molecules

Question 21

The infectious agents of prion diseases have little or no

Answer 21

Nucleic acid

Question 22

The protein of amyloid aggregates is encoded by the genome of the host. It is designated

Answer 22

PrP (Prion Protein)

Question 23

A glycoprotein found on the extracellular face of neuron plasma membranes, anchored to the membrane by covalent linkage to a molecule of a phosphatidyl inositol glycolipid

Answer 23

PrP

Question 24

Transcription of PrP and amino acid composition of PrP in infected and normal individuals are

Answer 24

Identical

Question 25

Explains the lack of an immune response: PrP and its derivatives are normal constituents of the body, to which the immune system should be tolerant

Answer 25

The prion hypothesis

Question 26

PrP fragments from the normal brain are rich in

Answer 26

α-helix (completely destroyed by proteases)

Question 27

PrP fragments from the infected brain are rich in

Answer 27

β-sheet (resistant to proteases)

Question 28

PrPC is in equilibrium with a rare, energetically unfavorable conformation, PrPC. PrPC principally reverts to PrPC but very rarely transforms to PrPSc. The altered conformation of PrPSc allows it to bind additional PrPC and catalyze its conversion to PrPSc. This is called

Answer 28

Prusiner’s hypothesis

Question 29

This is an autocatalytic process: once it begins the rate of conversion of PrPC to PrPSc continuously increases. PrPSc is proteolytically cleaved and the cleaved protein aggregates into amyloid fibrils

Answer 29

Prusiner’s Hypothesis

Question 30

Arises from rare spontaneous transformation of PrPC* to PrPSc

Answer 30

Sporadic prion disease

Question 31

Initiated by introduction of PrPSc from an exogenous source, i.e. consumption in the diet, contact with contaminated surgical instruments, organ transplants

Answer 31

Infectious prion disease

Question 32

Caused by mutations in the PrP gene. These increase the rate of spontaneous conversion of PrPC to PrPSc sufficiently that disease occurs in every person with the mutation

Answer 32

Inherited prion diseases

Question 33

When disease is transmitted from one species to another, the protein which accumulates in brain plaques should be that encoded by the genome of the host, not the

Answer 33

Species of origin

Question 34

A critical test of the Prion Hypothesis: PrPSc should convert

Answer 34

PrPC to PrPSC

Question 35

Heritable prion-like conditions exist in

Answer 35

Yeast and other fungi

Question 36

When disease is first transmitted from one species to another, the incubation time is longer than when the inoculum and the host are from the

Answer 36

Same species

Question 37

PrP 27-30 from different forms of human prion disease leads to formation of forms of PrP that differ in electrophoretic mobility and distribution in the

Answer 37

Brain

Question 38

If the infectious agent for prion diseases is a virus, then when compared to an ordinary virus, it must be far more

Answer 38

Stable

Question 39

This virus would also have to be able to interact in some way with

Answer 39

PrP protein

Question 40

All deaths from vCJD have been in persons homozygous for a specific allele of the human

Answer 40

PrP gene

Question 41

vCJD occurs in young people in contrast to classic sporadic CJD, which occurs in the

Answer 41

Elderly

Question 42

A prion disease of deer and elk, endemic in Colorado and Wyoming, which recently has begun to spread elsewhere

Answer 42

Chronic wasting disease