BIO 206SPRING SEMESTER 2019INSTRUCTOR: DR. RITA MOYES20 February 2019Prions● Discovered by Stanley Prusiner in 1982, nobel prize 1987● Proteinaceous infectious particle (an infectious protein)● Inherited and transmitted by ingestion, transplant, and surgical instruments○ Transmissible Spongiform encephalopathies: sheep scrapies■ Creutzfeldt-Jakob disease, Kuru, fatal familial insomnia● Human diseases■ Mad cow disease● Bovine SE (BSE)■ Produces holes into the brain■ Slow, persistent, deadly disease● PrPC: normal cellular prion protein, on cell surface○ In brain and nervous system○ Function??? Regulating cell death● PrPSc: scrapie protein○ Accumulates in brain cells, forming plaques (holes)○ Infectious proteins○ Exposed to prions→ prions act as a template→ refolds the normal proteins ina chain reaction● What is the difference between the normal protein vs. the prion?○ Conformational change■ Folded different● Can’t perform its reaction/function1○ Very resistant to enzymes■ Resistant to degradation● Outcome: neuronal damage in brain/CNS○ Death of the tissues/neuronsHuman SEKuru● Recognized in cannibalistic tribes in New Guinea● Progressive, fatal neurological disease● Affect CNS → mental derangement and loss of motor function● If tribe member died, the women prepare the body for burial○ Women would eat the brain○ Children at their feet● Kuru victims must be fed pre-chewed foodCreutzfeldt-Jakob Disease (CJD)● Extremely rare disease● Runs in families○ Inherited● Usually person > 50 years old when the symptoms start to show● Other ways CJD is acquired→ variable CJD○ Corneal transplant○ Growth hormones○ Surgical instruments (electrodes in the brain)Bovine Spongiform Encephalopathy (BSE)● First reported in Britain in 1986● Linked to supplementing cattle food with bone meal and tissues of sheep○ Some had scrapies● 1981 History2○ Change in manufacturing practice○ Eliminated treatment of feed with organic solvents■ Eliminated the important step that destroyed/inactivated any presentprions in tissues usedvCJD● transmitted , not inherited● 1996 (10 years later)○ 17 people in Great Britain diagnosed with CJD○ Ate beef contaminated with nervous tissue○ All very young ~ 20 years old○ Saw plaques in brain○ Found in PrP-sc● 1989- USA banned imported beef from Britain● 1997- USA banned used of beef and lamb in cattle and sheep food● 2009- USA increases BSE- related feed banChronic Wasting Disease in Deer and Elk● Expt: looked at cattle that grazed with elk/deer with CWD● Deer hunter eat meat from elk/deer● Prion spread → saliva, blood, urine → contaminated water/food○ Prion persists a long time in the environment● Present in antler velvetPrions● Transferred○ During corneal implants○ By growth hormones from cadaver pituitaries○ Surgical instruments● Resistant to:○ Formaldehyde○ Ethanol○ Proteases (enzymes)3○ Ionizing radiation○ Cooking to 662 degrees F● Sensitive to:○ Bleach○ Phenol○ Strong detergents○ Autoclaving organic solvents● Dairy is fine = no nervous tissue present● Gelatin is made from cattle products but is fully processedPlant Viruses and Viroids● Plant viruses:enters through wounds or via insects● Viroids: infectious RNA○ E.g. potato spindle tuber disease or Avocado sunblotch viroid■ Very small piece of naked RNA■ 1/10th size of RNA viruses■ Only associated with plant diseases● Linear and circular potato spindle tuber viroid