Chapter 18: Infectious Molecules: Prions and Viroids
Prions are highly resistant to decontamination, What methods are used to decontaminate against prions?
1 N NaOH or undiluted fresh household bleach followed by autoclaving at 132°C for 4.5 hours
What the ID50 for prions?
10^13 prions
How many people have died from vCJD since the start of the epidemic?
177
PRNP gene is located on chromosone _____ of humans
20
What is the incubation period of TSE's?
20-56 years. Unless acquired by cattle or vCJD which is shorter
PRNP code for a ________ amino acid protein
254
What are the intial symptoms of CJD?
Anxiety Memory loss Mood changes Depression Withdrawal
What are the names of the two families of Viroids?
Avsunviroidae and Pospiviroidae
How do Avsunviroidae and Pospiviroidae differ?
Avsunviroidae: Branched, "quasi" rodlike structure. Accumulate and replicate in chloroplasts.Lack a C region Pospiviroidae: True, rodlike secondary structure. Nuclear localization
What is the accepted hypothesis for the origin of BSE?
BSE came from cattle ingesting scrapie-contaminated bone meal derived from sheep offal fed to young calves
Cause of Kuru
Cannabilism
What is the name of the prion disease commonly found in deer elk and moose that causes emaciation, drooling and thirst, frequent urination and aspiration pneumonia?
Chronic Wasting Disease (CWD)
The cell's _____________________ synthesizes viroid RNA
DdRp3
T/F viroids replicate in the cytoplasm just like conventional plant RNA viruses
False
T/F Scrapie is a fairly new prion disease of sheep and goats that has really only been around for the last 20 years
False, it's been around for 250 years
T/F Prions are only in humans
False, they are in all animals
What are the three ways that TSE can Arise?
Infection, Inherited or Sporadic
Define Prions
Infectious proteins that do not have any nucleic acid that cause a group of diseases of the brain and nervous system called transmissible spongiform encephalopathies (TSEs)
Cause of Creutzfeldt-Jakob Disease (CJD)
Inherited germline mutation in PrP gene, sporadic or iatrogenic
Why is CWD only found in 15% of free range deer but about 90% of captive deer?
It is easily transmitted deer to deer, so if they are in captivity it is going to spread quickly
How did the very first case of Kuru probably happen?
It was probably a genetic disorder (mutation) about 10 years before the practice of cannibalism
What the final symptoms of CJD?
Loss of speech Stupor Coma Death 14 months after symptoms appear
Which viroid domain caused the symptoms of viroid infected plants
P
What leads to the induction of the interferon pathway?
PKR
What is the genetic link of susceptible a person is to a prion disease?
People who have Methionine at a specific location on the PRNP codon.
Which vegetables are more susceptible to PSTV?
Potatoes and tomatoes
What is the normal cellular form of PrP
PrPc (cellular)
Who reported that a yeast prion called Ure2p could change shape and cause other yeast proteins to change to a similar shape
Reed B. Wickner
Is it easier to transmit prions between different species or the same species?
Same species, except in the case of BSE which is easily transmitted to sheep
PRPsc is a disease common in sheep. What does the "sc" stand for?
Scrapie. The sheep become very itchy
What are the possibly functions of PrPc?
Signal transduction Cellular differentiation Cell adhesion Copper transport Might play a role in stress relief
Define Viroids
Small, pathogenic RNAs (+ssRNA, covalenly closed circular pathogenic molecules) that cause virus-like diseases in plants only. Do not have proteins or produce gene products
What brain changes can be expected in TSE victims?
Spongiform changes: Vacuoles (clear zones) similar to a sponge Neuronal loss: Apoptosis Amyloid plaques: Formation of PrPres threadlike aggregates
In 1972, who got a nobel prize for initiated research to isolate the infectious agent that caused Kuru and similar diseases
Stanley Prusiner
What are the 5 structural or functional domains of Viroids?
T1, P, C, V, and T2
T/F Plants can act as carriers of prions and play a tole in horizontal transmission of prion diseases
True
What are the neurological sign of CJD?
Twitching Spasms (jerky movements) Posture and gait abnormalities (motor difficulties)
Define TSE
cause a noninflammatory process that results in the vacuolation, or spongiosis, in the gray matter of the brain
Cause of Variant Creutzfeldt-Jakob Disease (vCJD)
consumption of contaminated beef (bovine prions)
Prions may also invade brain through ________________ of tongue
hypoglossal nerve
Cause of Fatal familial insomnia (FFI)
inherited germline mutation in PrP Gene
Cause Gerstmann-Straussler-Scheinker Disease (GSS)
inherited mutation in PrP gene
PrPc is commonly found in ___________
neurons
What anchors PrPc to the cell membrane?
phospholipid
How does PrPc become deleterious?
post-translationally misfolded into the infectious disease and resistant to (protease digestion) isoform denoted PrPres. It is targeted via a secretory pathway to the cell surface of neurons and other cell types. Over time, the PrPres accumulates into clumps that damage nerve cells in the brain
Viroids activate a plant dsRNA activated _________________
protein kinase called PKR
What does Prion stand for?
proteinaceous infectious particle
BSE is sometimes called __________________ disease because of the symptoms of aggressiveness and kicking
raging or mad cow
Neuroinvasion of the prions occurs by the _______________ from abdomen to the brain
vagus nerves
