Prions

Sterilization of Prions

*HARD TO KILL* -Infectious particles possesing Nucleic acid are dependent upon it to direct their continued replication -However, Prions are infectious by their effect on normal versions of the protein *Sterilization* involves *Denaturation* of the protein, so molecule is no longer able to induce the abnormal folding of normal proteins. *Resistant* to: Proteases, Heat, Radiation & Formulin treatments

Prions are composed of what molecule?

*Proteins* PrP-Prion Protein ---*NO RnA or DnA* Protein occurs in BOTH Infectious & Non Infectious form

All known *Prion* diseases, collectively called

*Transmissible Spongiform Encephalopathies* (*TSE*), UNTREATABLE & FATAL --Prion protein (PrP) similiar in all mammals contributes to transmission from animal to humans --PrP small differences between different species prevents transmission from 1 species to another --Outbreak in the 80's in England was traced back to infected meat

How can you get CJD?

-Genetic mutation of gene that codes for prion protein (PRNP). Occurs only 5-10% of cases -Iatrogenic transmission-Medical staff cause infection -Unknown transmission Brain is affected--->Brain stem

Prions Implicate

A number of diseases in a variety of mammals Ex: Bovine Spongiform Encephalopathy-BSE, aka *Mad Cow Disease* in cattle Creutzfeldt-Jacob Disease-CJD in humans caused by BSE

The word *Prion*

A portmanteu derived from the initials & final letters of the words *Pr*oteinaceous Infect*ion* *Prions* can cross species barriers

Prion disease

Affect structure of the Brain & or Neural tissue *UNTREATABLE/FATAL*

Creutzfeldt-Jakob disease CJD

Degenerative neurological disorder INCURABLE & FATAL *Most Common*: Transmission Spongiform Encephalopathy -*RARE*: effects 1 million people a year, age 45-75, more common 60-65 *Exception* vCJD-"varient", occurs in younger people

vCDJ

Caused by Prion that infect cattle w/ Bovine Spongiform Encephalopathy (BSE), transmitted through infected meat -France & England whole herds of cattle were put to death to prevent the spread of disease

KURU

Caused by Prions related to CJD--Known for epidemic in Papua, New Guinea in middle of 20th century & earlier -Cannabalism, consumption of person w/ sporadic CJD -Incubation/Asymptomatic phase, 5-20 years -Symptoms=Trembling in almost ALL patients w/ TSE, leads to Dimentia

*Stanley Prusiner*

Coined the word *Prion* as a name for the infectious agent -Won Nobel prize 1997

Sources of Prions in Humans

Humans before outbreak in Europe, Average age 60 *Creutzfeldt-Jacob disease*----CJD *Iatrogenic*--- iCJD (obtained from medical treatment) *Varient*--vCJD (English outbreak-Age 28, faster than average) *Familial*--fCJD (Genetic link) *Sporadic*--sCJD *Gerstmann-Staussler Scheinker disease*-- GSS *Fatal Familial Insomnia*--sFI *Kuru*--Tribe in New Guinea, Cannabals. Women & children ate last, usually the brain

Sterilization process of Prions

Immerse in a pan containing 1N NaOH and heat in a gravity-displacement autoclave at 121°C for 30 minutes; clean; rinse in water; and then perform routine sterilization processes

Prions are composed of

Mis-folded protein, does not self-replicate, Rather induces existing *Polypeptides* in the host of the organism to take on the rogue form --Rogue protein causes us to make more *Rogue* proteins

Prions cause

Neurodegenerative disease in CNS. Forms plaques called amyloid, disrupts normal tissue structure *DISRUPTION*- *Holes* in tissue, resulting in spongy architecture due to vacuole formation in the neurons *INCUBATION* period very long. Once symptoms appear, disease progresses rapidly. Ex: Convultions, Dementia & Ataxia (balance and coordination disfunction) -Also behavioral or personality changes

Chronic Wasting Disease

Origin & Mode of transmission of Prions UNKNOWN -*Recent*-Prions excreted by Deer & Elk, transmitted by eating grass growing in contaminated soil by *Saliva* -Affects animals born in captivity & the wild -Possible maternal transmission -Transmission lateral Animal to Animal

Sources of Prions

Scrapie- Scrape butts till raw CWD- Muscles become weak (Wasting)

KURU transmission

Spread easily & rapidly in the Fore people -Endocannibalistic funeral practices, relatives consume the deceased -Dysmorphism-Women & Children 8-9 times more likely to contract due to them being left to eat brain & spinal areas