Prions and other strange pathogens Flashcards

1
Q

What did the arrival of Europeans in the Carribean in 1492 lead to?

A

Largest human population replacement in the past 13,000 years
1492- 61 million people
1650- 6 million people

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2
Q

Why was there such a loss in population when the Europeans arrived in the Carribean?

A

Diseases carried by Europeans, plus war, enslavement and famine. Led to
Near-cessation of farming and reduction in fire use.
Regeneration of >50 million hectares of forest, woody savanna
and grassland.
Carbon uptake by vegetation and soils estimated at 5–40 Pg within around 100 years.

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3
Q

What process should kill a new host?

A

MHC incompatibility

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4
Q

What is the Tazmanian Devils- Devil facial tumour disease (DFTD)?

A

Schwann cell

Endangering the species

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5
Q

What is the dogs- canine transmissible veneral tumour (CTVT)?

A

From a dog

Roughly 11,000 yrs BP

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6
Q

What is the hamsters- reticulum cell sarcoma?

A

Transmissible by contact, material left of cage mesh and even by mosquitoes

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7
Q

How many women in the US get cancer each year while they’re pregnant?

A

3,500

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8
Q

What are some examples of cancers that have been passed from mother to foetus?

A

Melanoma
Acute leukaemia
Carcinoma

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9
Q

What are mimiviruses?

A

Have genes encoding repair enzymes, correct replication errors, produce mRNA transcripts from genes and translate those mRNAs into proteins

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10
Q

What is considered the hallmark of living things?

A

Informational genes

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11
Q

What do virusoids depend on?

A

Helper viruses which encapsulate them

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12
Q

What is Hepatitis B delta antigen encoded by?

A

A virusoid

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13
Q

What is the smallest genome for animal-infective pathogen?

A

Roughly 1700 nucleotides

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14
Q

What is the structure of virusoids?

A

Negative sense, single stranded, closed circular RNA

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15
Q

What are viroids?

A

Plant pathogens

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16
Q

What is the structure of viroids?

A
RNA genome
smallest known- 220 nucleotides of RNA
Single stranded, covalent circle
Extensive intra-molecular pairing 
No protein encoded
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17
Q

Are helper virus needed for replication in viroids?

A

No

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18
Q

What makes both strand in viroids?

A

A DNA directed RNA polymerase

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19
Q

What activity do both viroids and virusoids do?

A

Ribozyme activity

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20
Q

What are examples of diseases of protein misfolding?

A

Alpha-synuclein – in Parkinson’s diseease
Beta-amyloid – in Alzheimer’s disease
Both prion-like.
Transmissible protein aggregation/misfolding -

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21
Q

What are prions?

A

Pathogen appears to be comprised of protein only

No genetic nucleotide material involved

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22
Q

What do prions cause?

A

The transmissible spongiform encephalopathies (TSEs)

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23
Q

What is the shape of prions?

A

Prions are aberrantly or misfolded forms of normal cellular proteins

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24
Q

What do prions contradict?

A

‘central dogma of molecular biology’

25
Q

where is scrapie found?

A

in sheep and goats

26
Q

where is Bovine Spongiform Encephalopathy (BSE) found?

A

in cattle - mad cow disease

27
Q

what was the first prion disease described in humans and shown to be transmissible?

A

Kuru (in Papua New Guinea)

28
Q

what are the Creutzfeldt-Jakob disease (CJD) varieties?

A
  • iatrogenic (iCJD)
  • variant CJD (vCJD or nvCJD) - derived from BSE
  • familial CJD (fCJD)
  • sporadic CJD (sCJD)
29
Q

is human CJD derived from scrapie of sheep?

A

no

30
Q

when was the Kuru epidemic originated?

A

around 1900 from a single individual thought to have spontaneously developed some form of CJD

31
Q

what did the endocanibalistic funeral practices consisted of?

A

relatives consumed the bodies of the deceased to return the life force

32
Q

where there any gender differences in the prevalence of Kuru?

A

8/9 times more prevalent in women and children than in men

33
Q

why was Kuru more prevalent in women and children?

A

because they ate the rest of the body, including the brain, and took the task of cleaning relatives after death - may have had open sores and cuts

34
Q

can humans get nvCJD from scrapie of sheep

A

not directly

35
Q

how does cattle get BSE?

A

from sheep scrapie

36
Q

how can humans get nvCJD?

A

from BSE

37
Q

what is amyloid?

A

insoluble fibrous protein aggregates sharing specific traits

38
Q

what is characteristic of CJD?

A

vacuolation of the neural tissue - amyloid accumulation

39
Q

what does the intracellular process thought to cause?

A

the production and accumulation of improperly folded PrP protein

40
Q

to what is the transmissible trio protein resistant?

A

is highly resistant to digestion proteinases (proteinase K)

41
Q

what is PrPc?

A

normal cellular prion protein

42
Q

what is PrPSc?

A

abnormal prion/scrapie protein

43
Q

what evidence is there that supports the protein-only hypothesis?

A
  • no virus particles, bacteria, fungi associated with prion diseases
  • no nucleic acid has been conclusively associated with infectivity- agent is resistant to ultraviolet radiation
  • no immune response to infection
  • PrPSc experimentally transmitted between one species and another results in PrPSc with the amino-acid sequence of the recipient species - replication of the initial infectious agent does not occur
44
Q

what other evidence is there for the protein-only hypothesis?

A
  • familial prion disease occurs in families with a mutation in the PrPc gene
  • mice with PrPc mutations develop prion disease despite conditions where transmission is prevented
  • animals lacking PrPc do not contract prion disease gene if infected
  • infectious prions can be formed de novo from purified non-infectious components, in the absence of gene-coding nucleic acids
45
Q

how do we get nvCJD?

A

injections, surgery, transfusions, needles or electrodes, dentistry

46
Q

how does nvCJD spread?

A
  • oral - very quickly proliferates in tonsils

- enterocytes - M cells and dendritic cells required for/enhance dissemination to the CNS

47
Q

where can prions propagate?

A

in the lymphoreticular system (spleen, lymph, nodes, tonsils, appendix, and other gut-associated lymphoid tissues)

48
Q

what can the propagation of prions lead to?

A

neuroinvasion

49
Q

what age group is more susceptible to nvCJD?

A

females - 20-24

males - 25-29

50
Q

what is the genetic susceptibility in humans?

A
  • M129 - methionine at position 129 - early onset Kuru
  • heterozygotes amongst long term survivors of Kuru
  • V129 resistant to nvCJD
51
Q

what are the prevention measures for nvCJD?

A
  • cattle for consumption killed young -27 months
  • limitation on which parts of an animals can enter food chain
  • sterilisation procedures improved
  • blood products - policy changes
52
Q

what are prions quite resistant to?

A

denaturation by proteinases, heat, radiation and formalin

53
Q

how can prions be denatured?

A

at 134ºC for 18 mins in a pressurised steam autoclave

54
Q

can denatured prions be renatured?

A

yes- to an infective status under certain artificial conditions

55
Q

what does the WHO recommends?

A
  1. immersion in 1N NaOH and heating at 121ºC for 30 mins; clean; rinse in water; and then subject to routine sterilisation
  2. immersion in 1N NaOH or sodium hypochlorite for 1h; transfer instrument to water; heat for 1h; clean; and hen subject to routine sterilisation
  3. immerse in 1N NaOH or sodium hypochlorite for 1h; remove and rinse in water, then heat to 121ºC or even 134ºC autoclave for 1h; clean; and then subject to routine sterilisation
56
Q

to what is scrapie infectious?

A

not directly to humans

infectious to cattle and hence to humans (causing nvCJD)

57
Q

what are prions?

A

abnormal versions of a normal protein

58
Q

how do prions spread?

A

by transforming normal proteins with which they come into contact into abnormal versions

59
Q

where can this occur?

A

in the brains of parkinson’s disease