PRIONS
Kalina Estrada
TA: Yu-Chen Hwang
Thursday, 7-8pm
Background
• PRIONS ARE NOT VIRUSES- they don’t
contain genetic material
• “Prion” - short for proteinaceous infectious
particle (coined by Prusiner), made ONLY
of protein. Therefore, they are resistent to
nucleases, but not proteases.
• The specific protein that the prion was
made of was named PrP, an abbreviation
for "prion-related protein".
History
• 1730’s: 1st appearance in Sheep
• 1950’s: High levels of Kuru appear among the Fore people of New
Guinea.
• 1960’s: found to be contagious
• 1980’s: 60 people died from CJD, after being infected by
contaminated surgical instruments
• 1982: Prusiner found these diseases to be caused by a protein
• 1985: Scientists found that uninfected individuals produce the
normal PrP genes
• 1987: Mad Cow Disease. By 2000, approx. 180,000 cattle were
found infected, and most were killed (to prevent further
contamination)
• 1996: Mad Cow beef proves to be fatal to people. By April 2005, 155
U.K. resisdents died.
Structure
•
There are two forms of
PrP (for the most part
made up of the same
amino acids):
1. PrP-sen (on the left): is
produced by normal
healthy cells. Sen stands
for “sensitive” because it is
sensitive to being broken
down
2. PrP-res (on the right): is
an isoform- the disease
causing form. Res stands
for “resistant” because it is
resistent to being broken
down.
Replication
• Unlike other infectious
particles or viruses,
Prions do not contain a
nucleic acid genome.
However, once a prion
has infected, it can
replicate
• Although it has not been
confirmed, evidence
shows that when PrP-sen
comes into contact with
PrP-res it is converted to
PrP-res, by dimerizing.
This results in a chain
reaction of PrP-sen
isforming into PrP-res.
How they infect…
• Because of their abnormal shape, PrP-res
proteins tend to stick to each other. Over time,
the PrP-res molecules stack up to form long
chains called “amyloid fibers”.
• Amyloid fibers are toxic to cells, and ultimately kill
them.
• Astrocytes crawl through the brain digesting the
dead neurons, leaving holes where neurons used
to be. The amyloid fibers remain.
• This causes holes in the brain which can
ultimately lead to death.
Prions are contracted in a few
different ways:
• Eating tissue infected with
PrP-res
• An inherited mutation in the
gene that encodes for
normal PrP
• Spontaneous formation of
PrP-res (rare)
Transmission Cycle
PrP-BSE
PrP-Scr
PrP-vCJD
Some Examples of Prions
(spongiform diseases):
• Scrapie (sheep- PrP-Scr)
• Bovine Spongiform
Encephalopathy (BSE,
a.k.a. Mad Cow
Disease,1987)
• Kuru (transmitted through
consumption of human
brain tissue)
• Creutzfeld-Jakob disease
in humans (CJD)
• Encephalopathy of mink
Any treatment?
• There is no immune response to pathogen
• Spongiform diseases are contagious and
have a long incubation period
• Spongiform diseases are fatal and
untreatable
• There are no effective treatments
• Symptoms vary depending on the
concentrated area
Prevention
• Do not eat infected tissue
• Make sure when undergoing or performing
surgical procedures, to use sterile utensils.
• Prions are not easily destroyed. The use of
boiling techniques, alcohol , acid, standard
autoclaving methods, or radiation will not kill
them.
• “ In fact, infected brains that have been sitting in
formaldehyde for decades can still transmit
spongiform disease.”- University of Utah, 2006
• Cooking your burger until it's well done will not
get rid of the prions!!
References
• University of Utah, Genetic Science learning
center, 2006
http://gslc.genetics.utah.edu/features/prions/kuru
.cfm
• Research in the News: Prions - Puzzling
Infectious Proteins, National Institutes of Health,
1997 http://scienceeducation.nih.gov/home2.nsf/Educational+Reso
urces/Resource+Formats/Online+Resources/+Hi
gh+School/D07612181A4E785B85256CCD0064
857B