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-Scr

PrP-BSE

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://science-education.nih.gov/home2.nsf/Educational+Resources/Resource+Formats/Online+Resources/+High+School/D07612181A4E785B85256CCD0064857B