Prions have extraordinary biological characteristics, not the least of which is their possible non-existence.
Infectious Particles
Agent Hypotheses
Dominant belief
Normal host prion protein (PrP) spontaneously converts into an infectious amyloid, i.e., a “prion”;
Alternative view
TSE agents are environmental pathogens with a genome that encodes different agent strains;
These infectious agents need cell PrP to survive, and they provoke PrP amyloid as a late defense mechanism.
A) no infection without PrP host receptor; B) most agents induce same PrP-res; C) Amyloid stymies agent
Current Status (3/2014)
Attempts to fabricate an infectious PrP in a test tube
No reproducible infectivity for any pure PrP, including recombinant PrP (rPrP); more than 100 independent experiments fail to generate any infectivity from rPrP
Update: Dec 2015 Collinge lab reported 20,000 failed attempts to make rPrP infectious (Open Biol. 2015 Dec;5(12):150165. doi: 10.1098/rsob.150165) in contrast to previous Science publications.
Additional new data
- Removal of PrP in brain homogenates does not reduce the infectivity PMID 21793014
- When the “infectious” PrP amyloid increases, infectivity falls by 10,000 fold PMID 22509412
- All infectious preparations contain circular DNAs of >500nt by molecular analysis PMID 21165784
- CJD and scrapie agent particles, as viral structures, require nucleic acids to infect cells Download PDF
- Infectious particles, stress, and induced prion amyloids Download PDF
- Continuous production of prions after infectious particles are eliminated Download PDF
Are "established" Prion claims accurate?
|
Claim |
Experiment |
Comment |
|
1) "PrPSc (PrP-res amyloid) is proportional to titer" |
FALSE |
diverse data from many labs falsify |
|
2) "Procedures that hydrolyze PrPSc inactivate prions" |
TRUE |
These also inactivate viruses |
|
3) "No evidence exists for a virus-like particle" |
FALSE |
discrete ~25nm viral particle |
|
4) "Transmissible particles are devoid of nucleic acid" |
FALSE |
all infectious matter contains long DNA |
|
5) "PrP gene mutations cause formation of PrPSc" |
FALSE |
toxic pathology, but not PrPSc |
|
6) "PrP gene mutations cause transmissible disease" |
FALSE |
Contamination with scrapie & irreproducible |
|
7) "Prion diversity is enciphered by PrPSc" folding |
FALSE |
unfolding PrP-res: no effect on strain or titer |
|
9) "No immune response to foreign agent" |
FALSE |
Early innate immune responses before PrP-res |
|
10) "PrPSc associated with pathology" |
TRUE |
PrPSc is a late response to infection |
|
11) Protein X binds PrP to make it infectious |
X not found |
PrP itself not infectious; X is probably a virus |
|
12) "Prions defy the rules of protein structure" |
TRUE |
also of thermodynamics |
|
13) CJD infectious agent arises spontaneously |
No evidence for |
An old & disproven concept of infection |
|
14) recombinant PrP can be made infectious |
FALSE |
Irreproducible: numerous failed attempts |