Infectious Particles

Concepts & Facts

The Force of Prions

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.




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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

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

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