Prions and the other...

Question 1

Transmissable tumours

Answer 1

• tumours are genetically different from hosts
• down -regulate MHC - but why not then killed by NK cells
• tazmanian devils - Devil facial tumour disease (DFTD) Schwann cell
• Dogs -canine transmissible venereal tumour (CTVT)

Question 2

the spongiform encephalopathies of humans (e.g. Kuru and CJD) and wild and domestic animals (e.g. ‘mad cow disease’), controversy about the nature of the transmissible agents, the prion hypothesis.

Answer 2

ILOS

Question 3

TSEs (Transmissible spongiform encephalopathy)

Answer 3

• scrapie in sheep and goats

- bovine spongiform encephalopathy (BSE) in cattle (mad cow disease)

Question 4

TSE’s of humans

Answer 4

• sporadic, inherited, or acquired
• Kuru - papa new guinea, first prion disease described in humans and shown to be transmissible
• human CJD is probably not derived from scrapie of sheep directly

Question 5

CJK - Creutzfeldt-Jakob disease

Answer 5

• iatrogenic iCAD
• variant CJD (vCJD or nvCJD)
• familial CJD (fCJD)
• sporadic CJD (sCJD)

Question 6

Kuru

Answer 6

• cannibilism
• 8-9 times more prevalent in women
• cleaning the dead bodies - open sores?

Question 7

Species jumping

Answer 7

• humans do not get vCJD directly from sheep
• cattle get BSE from sheep scrapie
• humans then get nvCJD from BSE
• are also cases of silent prion infection in some species

Question 8

Prion only hypothesis

Answer 8

proofs:

• prion protein-negative mice are resistant
• brain transplant expt.
• problems:
• diff. strains of the agent exist in the same species (scrapie), producing different pathologies and cause disease with different time courses
• genetic susceptibility varies in humans and animals
• koch’s postulates -can artificially -generated infective prion protein cause disease

Question 9

Evidence in favour of prion only hypothesis

Answer 9

-no virus particles, bacteria, fungi associated with prion diseases
- no nucleic acid
-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
• 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 even if
infected.
• Infectious prions can be formed de novo from purified non- infectious components, in the absence of gene-coding nucleic acids.

Question 10

Genetic susceptibility in humans

Answer 10

• M129 – methionine at position 129 - early onset Kuru
• Heterozygotes amongst long term survivors of Kuru
• V129 resistant to nvCJD
• Cannabalistic past?

Question 11

Sterilisation

Answer 11

• Prions are quite resistant to denaturation by proteinases, heat, radiation and formalin.
• Can be denatured at 134 °C for 18 minutes in a pressurised steam autoclave.
• But, partially denatured prions can be renatured to an infective status under certain artificial conditions.