The document discusses prions, which are proteinaceous infectious agents that can propagate and spread among hosts without a nucleic acid genome. It outlines the characteristics, requirements for self-propagation, and mechanisms of spread (vertical and horizontal) in both yeast and mammalian systems. Additionally, it notes examples of prion diseases and highlights similarities with misfolded proteins associated with various other neurodegenerative disorders.

1. • Characteristics:
 Proteinaceous infectious agent that lacks a specific nucleic acid genome
 A protein-based element of inheritance
• Basic requirements:
 A self-propagating state of a protein (the prion) that is biologically accessible, but rarely
accumulates spontaneously.
 Replication by acting on the non-prion state of the protein
 Capacity to spread to naïve hosts and find new substrate pools for replication.
• Examples
 Yeast/fungal prions
 Mammalian TSE prions
Prions
Fragmentation
More prions
Prion state
Non-prion
state
+
conformational
conversion

2. Yeast prion propagation
• spontaneous formation (rare)
• vertical spreading via cell division
• horizontal spreading via cytoplasmic exchange (e.g. mating)
Sup35-GFP in yeast cells
Serio and Lindquist 2000
prion-free prion-infected
spontaneous
mating/
cytoplasmic
mixing
prion
amplification &
cell divisionVertical
Horizontal

3. Transmission cycle for a
naturally spreading
mammalian prion disease:
Chronic wasting disease
Kraus, Groveman & Caughey, Ann Rev Micro 2013
Horizontal spread contributes to
local prevalences of up to 30% in
free-ranging deer

4. Spectrum of prion-like characteristics of misfolded proteins in mammals?
Non-prion protein misfolding
• cytoplasmic propagation
(only) • intracellular propagation
• cell-to-cell propagation
• tissue-to-tissue propagation
• naturally transmissible
• no self-propagation of misfolding within
cell or organism
• no transmission between individuals
Yeast prion TSE (CWD) prion
• Other TSE diseases
• experimentally or iatrogenically
transmissible
• Alzheimer’s
• type II diabetes
• Parkinson’s
• Huntington’s
• amyotrophic lateral sclerosis
• tauopathies
• sickle cell anemia
• cystic fibrosis
• secondary amyloidoses
• spinocerebellar ataxias
• AA amyloidosis
• apolipoprotein AII amyloidosis
• many others
?