Prions and other Nonviral infectious particles

Prions

• Infectious proteins whose extracellular form contains only protein, no nucleic acid

• Known to cause disease in animals → class of infectious diseases called transmissible spongiform encephalopathies
  (TSEs)
  • No plant prion diseases discovered yet

• Noncellular infectious agents
  • NOT VIRUSES! → May be own unique category

The exact mode of infection for prions is ___________.

still being investigated

• Until their discovery it was considered impossible that an agent lacking genetic material could be infectious or transmissible

• Inherited and transmissible by ingestion, transplant, and surgical instruments

Prion infection cycle

• The host contains a gene, Prnp (Prion protein), is primarily found in neurons (especially the brain)

• Native form of the prion PrP^C (prion protein Cellular)

• Pathogenic form of the prion protein is PrP^Sc (prion protein Scrapie)
  • Identical amino acid sequence to native form, but has a different conformation
  • The pathogenic prion “replicates” by converting preexisting native prions into the pathogenic form.

  
  
  

Prion Infection Cycle (cont.)

• As the pathogenic prions accumulate and aggregate, they form insoluble crystalline fibers referred to as amyloid plaques in neural
  cells

• Plaques are used for postmortem diagnosis, but they don’t appear to be the direct cause of cell damage

Besides the transmissible spongiform encephalopathies, amyloids are also associated with __________.

debilitating human diseases such as
Alzheimer’s, Huntington’s, Parkinson’s, and type 2 diabetes.

• The possibility remains that these diseases are manifestations of prion infection, but no direct link has currently been made.
  
  

Human Prion Diseases

1. Creutzfeldt-Jakob Disease (CJD)
2. Variant Creutzfeldt-Jakob Disease (vCJD)
3. Gerstmann-Straussler-Scheinker Syndrome
4. Fatal Familial Insomnia
5. Kuru

Animal Prion Diseases

1. Bovine Spongiform Encephalopathy (BSE)
2. Chronic Wasting Disease (CWD)
3. Scrapie
4. Transmissible mink encephalopathy
5. Feline spongiform encephalopathy
6. Exotic ungulate spongiform encephalopathy

Creutzfeldt-Jakob Disease (CJD) - Classical

• Neurodegenerative disorder → rapidly
  progressive → 100% mortality rate
  • not related to “mad cow” disease

• In most patients (85%) CJD occurs sporadically
  • Minority of patients develop CJD due to
  inherited mutations of the prion protein gene
  • Inherited forms include: Gerstmann-
  Straussler-Scheinker syndrome and fatal
  familial insomnia

  
  
  

Kuru

• Epidemic occurrence in the 1950s-60s
  among the Fore people of Papa New
  Guinea

• Result of ritualistic cannibalism

• Government discouragement of the
  practice of cannibalism led to a continuing decline in the disease, which has now mostly disappeared.

  
  
  

Bovine Spongiform Encephalopathy (BSE)

• Neurodegenerative disorder → rapidly progressive → 100% mortality rate

• Organism: Cattle
  • First infections occurred in the 1970s (identified in 1986)
  • Cases in UK have dropped sharply (>14K in 1995 to 2 in 2015)

• Possibly originated as a result of feeding cattle meat-and-bone meal that contained BSE-infected products from a spontaneously occurring case of BSE or scrapie-infected sheep products

  • Laws in developed countries now ban the use of rendered ruminant proteins in ruminant feed as a precaution against the spread of prion infection in cattle and other ruminants.

Creutzfeldt-Jakob Disease (vCJD) - Variant

• First described in 1996 in the United Kingdom

• Strong evidence that agent responsible for vCJD in humans is the same agent responsible for BSE in cows

• Different clinical and pathologic characteristics from classic CJD

  • Each disease has unique genetic profile of the prion protein gene

Chronic Wasting Disease (CWD)

• Affects deer, elk, reindeer, sika deer and
  moose
  • No reported cases in humans,
  though it may pose a risk to
  certain non-human primates
  • Spread by saliva, blood, urine, feces.
  Possibly soil, water and food
  • Found in Canada, United States,
  Norway, Finland, Sweden, and South
  Korea

• Fatal to animals and there are no
  treatments or vaccines
  • does not appear to naturally infect
  cattle or other domesticated animals.

  
  
  

Satellites: Viruses & Nucleic Acids

• subviral particles

• No common phylogeny → Grouped on common characteristics
  • Dependent on other viruses for replication

Satellite Virus vs Satellite Nucleic Acid

• Satellite virus → Encode their own capsid protein

• Satellite Nucleic Acid → No capsid protein

Hepatitis D

• Requires viral particles from hepatitis B virus (HBV) to replicate

• Worsens the severity of liver damage

• Found globally → predominantly in Africa, Middle East, and southern Italy

• Has the highest fatality rate of all the hepatitis infections, at 20%

Hepatitis is a liver inflammation, commonly caused by an infectious agent. Hepatitis sometimes results in _________.

acute illness followed by destruction of functional liver anatomy and cells, a condition known as cirrhosis.

• Hepatitis due to infection can cause chronic or acute disease, and some forms lead to liver cancer.
  
  

The vaccine for hepatitis B protects against hepatitis D virus because of the ____________.

latter's dependence on the presence of hepatitis B virus for it to replicate.

Viroids

• Virus-like agents that parasitize plants
  • Enters through a plant wound
  • About one-tenth the size of an average virus

• Composed of naked strands of RNA, lacking a
  capsid or any other type of coating

• Significant pathogens in economically important plants: tomatoes, potatoes, cucumbers, citrus trees, chrysanthemums

Which of the following is a human prion disease?

Creutzfeldt-Jakob Disease

Variant Creutzfeldt-Jakob Disease (vCJD) is linked to:

Bovine Spongiform Encephalopathy (BSE)

The satellite virus hepatitis D relies on which virus for replication?

Hepatitis B

Viroids are infectious agents that:

Parasitize plants