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: 1 st 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, Research in the News: Prions - Puzzling Infectious Proteins, National Institutes of Health, education.nih.gov/home2.nsf/Educational+Reso urces/Resource+Formats/Online+Resources/+Hi gh+School/D A4E785B85256CCD Bhttp://science- education.nih.gov/home2.nsf/Educational+Reso urces/Resource+Formats/Online+Resources/+Hi gh+School/D A4E785B85256CCD B