Prions & Viriods Flashcards

Question

What is the Pathogenesis of TSEs?

Answer 1

Incubation period of TSEs is long 20 to 56 years with the exception of vCJD South Fore tribe members still getting Kuru some 39–56 years after the cessation of cannibalism

Answer 2

Infected brains become spongiform (the brain has vacuoles—clear zones, similar to a sponge) ## Footnote Neuronal loss Astrocystosis (spread of astrocytes to damaged tissues in the brain) Amyloid plaques—formation of PrPres threadlike aggregates

Answer 3

The different TSEs can affect different regions of the brain Results in different symptoms

Answer 4

Depends upon what region of the brain is affected e.g., memory is affected when the cerebral cortex is infected Precise mechanism leading to brain damage is unknown No inflammation or immune defense against prions exists. Natural proteins (body does not recognize as foreign antigens) Prion proteins are only harmful when they are converted to PrPres.

Answer 5

Knockout mice that do not express PrPC are resistant to scrapie infection. PRNP gene lacking octarepeat copper binding motif was introduced into knock-out mice. Mice became susceptible to scrapie infection. Is copper binding unimportant in pathogenesis? Other copper binding sites exist outside of the octarepeat region; do these play a more important role in copper metabolism?

Answer 6

Free copper radicals are toxic to cells and are usually scavenged Radioactive copper was added to cells expressing the PRNP gene. Radioactive copper bound to the PrPC. PRNP expressing cells were more resistant to copper toxicity and oxidative stress compared to cells that did not express PRNP. PrPC may play a role in cleaning up free radicals (cellular scavenging mechanisms) Loss of PrPc function may change copper balance and cause oxidative damage throughout the brain

Answer 7

50 known mutations in the PRNP gene known to result in spontaneous PrPres formation PRNP codon 129 appears to act as a genetic susceptibility factor codes for methionine or valine at position 129 of the PrPC All people suffering from vCJD acquired through consuming prion-contaminated beef products were homozygous methionine at codon 129. Methionine homozygosity associated with rapidly progressing dementing disease

Answer 8

No drug therapies are available. Congo red B sheet breakers siRNAs Treatment is supportive. No vaccine is available. Anti-PrP antibodies inhibit prion replication in cultures cells Passive immunization delayed onset of disease in mice PrPC antibodies injected into the brains of mice cause neurotoxicity (safety concerns)

Answer 9

Transmissibility among species is easy. Transmission can occur between different species. High degree of amino acid sequence homology between species increases efficiency Origin of BSE is unclear. Accepted hypothesis is that BSE came from cattle ingesting scrapie-contaminated bone meal derived from sheep offal fed to young calves. Offal contains brain, spleen, thymus, tonsils, guts

Answer 10

Scrapie was considered a rare disease of sheep that did not cause disease in humans. Scrapie has been a disease of sheep and goats in United Kingdom and Western Europe for more than 250 years. First case in the U.S. was in 1947 Michigan flock of sheep Sheep of British origin imported through Canada Australia and New Zealand are still scrapie-free.

Answer 11

First diagnosed in 1985 Dairy farmer in England notices several cows with abnormal behavior Unsteady gait Aggressiveness Kicking during milking The term raging or mad cow disease was coined.

Answer 12

Difficulty in rising from a lying position Itching Heightened sensory perception Anorexia Excessive licking Decreased milk production ## Footnote Symptoms last for 2–6 months before the animal dies.

Answer 13

By June 1990 14,324 cases of BSE confirmed out of 10 million cattle ## Footnote Since 1986, over 200,000 cattle in the U.K. have developed mad cow disease 1–3 million were likely to have been infected with the BSE agent U.K. implemented control measures that included culling of sick animals the banning of all bovine materials from the food fed to cattle 1443 case in 2000 down to 11 cases in 2010

Answer 14

First described in the U.K. in 1996 10 people had died from a new form of CJD Believed to be caused by the ingestion of BSE-contaminated cattle products Time frame consistent with incubation period (1984-1996) As of April 2011, 171 deaths of vCJD patients reported in the U.K. 47% of UK population estimated to have methionine homozygosity (MM)

Answer 15

* The nation's 4th case of bovine spongiform encephalopathy confirmed in a dairy cow in central California on April 24, 2012 * Baker Commodities Inc. renders animal byproducts and had randomly selected the animal for testing * Initial testing at UC Davis was inconclusive * Subsequent testing at USDA was positive for atypical BSE (not from infected feed) * Infected cow unlikely to spread disease * USDA regulations prohibit high-risk parts of the cow, such as brains and spinal cords, from entering the food chain * Disease cannot be transmitted via milk * CDC: odds of a person contracting mad cow disease are \< 1 in 10 billion * 29 cases of BSE were reported worldwide in 2011 * down 99% since the peak of 37,311 cases in 1992

Answer 16

* Prion disease of deer, elk, and moose (rare) * Symptoms: * Chronic weight loss (ribs showing) * Blank facial expression * Excessive drooling and thirst * Frequent urination * Teeth grinding * Holding head in lower position * Nervousness * Sluggish behavior * Isolation from the herd * Poor hair coats * Animals appear emaciated, starving, or “wasting away.” * Some animals die from aspiration pneumonia

Answer 17

1978: researchers classified CWD as a TSE First cases in free-range elk and deer in northern Colorado, adjacent parts of southern Wyoming Spread to South Dakota, Wisconsin, etc. 2010: spread to 16 U.S. states, and Alberta, Saskatchewan, Canada Imported cases in South Korea

Answer 18

CWD incidence * 15% in free-ranging deer * 90% in captive deer * Incubation period ~5 years Transmission * Direct animal-to-animal contact * Indirect transmission (contaminated water or feed) * Saliva * Feces * Blood * Decomposing tissues * Urine

Answer 19

CWD more likely to occur where deer or elk congregate at artificial feeding, watering, and birthing areas PrPCWD remain infectious in the soil for at least two years Makes them difficult if not impossible to eliminate from the environment

Answer 20

Diagnosis: immunocytochemistry on tissues from obex portion of the animal’s brain No certified testing for live animals Management has become a major concern Deer hunting Game farmers

Answer 21

* Wear latex/rubber gloves when field dressing carcasses * Carefully bone out the meat of the entire carcass * Catchphrase: “no skull, no backbone.” * Prions concentrated in nervous tissue * Evidence that antler velvet from CWD-infected elk contain prions

Answer 22

Cluster of patients investigated Three young patients diagnosed with CJD between January 1997 and May 2000 All ate venison but none of the patients had eaten deer or elk in CWD endemic areas; CDC ruled out zoonotic transmission ## Footnote Laboratory results have been variable. Injecting ferrets intracerebrally with PrPCWD, 100% were susceptible Feeding the ferrets with PrPCWD, none were susceptible

Answer 23

Early work by Richard F. Marsh Two squirrel monkeys injected with infected intracerebrally with mule deer brain homogenate developed a TSE-like disease. Research by Race et al. Squirrel monkeys injected or fed CWD-positive homegenates developed TSE (11 out of 13). Cynomolgus macaques did not (8+ yrs) these monkeys are evolutionarily more similar to humans Raises the question that CWD might not be infectious to humans

Answer 24

Viroids are small RNA molecules that infect plants in the same manner as conventional plant viruses +ssRNA, covalently, closed circular pathogenic molecules Internal base-pairing Discovered in Theodor Diener 1971 Viroids do not code for any proteins. Viroids depend upon the plant host enzymes for their replication and other functions.

Answer 25

Avsunviroidae Branched, ‘quasi’ rod-like structure Accumulate and replicate in chloroplasts ## Footnote Pospiviroidae True rod-like secondary structure Nuclear localization Viroids contain 5 structural or functional domains Central ( C ) Pathogenicity (P) Variable (V) Two terminal domains (T1 and T2)

Answer 26

Viroids do not replicate in the cytoplasm like conventional plant RNA viruses. Viroids traffic within the cell through the nuclear pores using a host nuclear localization protein that binds to viroid RNA. Viroids replicate in either the nucleus or chloroplast of the plant. The cell’s DNA-dependent RNA polymerase III synthesizes viroid RNA in the nucleus.

Answer 27

Cellular RNA polymerase makes copies of viroid Longer (+) strand RNA than synthesized Enzymatic self-cleavage cuts long strand into multiunit +ssRNAs (ribozyme) Host RNA ligase causes circularization

Prions & Viriods Flashcards

(52 cards)