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Flashcards in Rabies & Prions Deck (16):
1

How is the "Rabies" virus classified?

"Rhabdovirus" Includes two genera:

  • Lyssavirus (Greek for rage) included Rabies
  • Vesiculovirus
    • vasicular stomatitis virus of horses, cattle, and pigs, can cause flu-like disease in lab workers.

 

2

Rabies Virion Morphology 

  • Shape: 
  • What is under the membrane? 
  • Genome type: 
  • Proteins associated w/ genome: 

  • rod or bullet shaped 
    • envelope with membrane spikes of viral glycoprotein 
  • under membrane is the matrix (M) protein, then the nucleocapsid of (-) ssRNA and protein that is helically coiled, giving striated look in EM.
  • RNA genome 
    • single-stranded, antisense polarity containing 5 genes (G, M, NS, L, and N)
  • RNA genome associated with three proteins:
    • Nucleocapsid (N) coats RNA
    • NS and L proteins form the RNA polymerase.

3

How does rhabdovirus replicate?

(long card....)

Prototype for (-) sense RNA viruses

  1. envelope (G) can bind cell via several receptors:
    • nicotinic acetylcholine receptor in muscle, ganglioside
    • CD56 in neurons
  2. virus is endocytosed and envelope fuses at low pH w/ endosomal membranes to release nucleoprotein
  3. virion-associated RNA-dependent RNA polymerase initiates transcription in 3' leader of (-) RNA, adds a cap, and "stutters" to make 5 polyadenylated mRNAs by reinitiation
    • At this stage, the RNA polymerase is not "processive"
  4. Viral proteins are made from the mRNAs
  5. Viral polymerase must switch from 'mRNA mode' to making full-length (+) RNA, which will serve as a template for (-) genome production
    • switch is due to buildup of N protein, which allows N to bind the polymerase
  6. With protein and genomes present, viruses then assemble
  7. G protein is inserted in the host cell membrane, and various components (M, RNA, N, NS, L) coalesce to assemble new virions, which bud from cell and acquire a membrane envelope in the process

4

  • How many serotypes exist for rhabdovirus?
  • Which viral protein elicits neutralizing antibodies?

  • 1 viral serotype
    • several 'strains' from different animal species and locations can be identified due to genetic variation
    • distinguished by monoclonal antibodies or sequence information 
  • G glycoprotein elicits neutralizing antibodies, but natural 'timing' of antibody production is not protective 
    • Antigenicity of G protein allows for vaccine production

5

entry is usually through a _____ or ____ ________ via a bite and introduction infected saliva

  • How else can rhabdovirus be transmitted?

entry is usually through a wound or skin abrasion via a bite and introduction infected saliva

  • can be transmitted by infected cornea transplants, and more recently from organ transplants
  • 1 reported case of arerosol infection in cave explorers

6

  • Where does rhabdovirus replicate during the incubation period?
  • How long is the incubation period?

  • virus replicates in muscle or connective tissue during "incubation" period
  • Length: can be months

7

Describe how rhabdovirus gets from the muscle to the brain and disseminates:

  • virus enters peripheral nerves at muscle and is carried through axons to the CNS, and brain rapidly becomes infected
    • Movement is 8-20mm/day
    • Intervention before spread to CNS is effective
  • virus replicates to high levels in the brain 
  • disseminates to numerous distal sites via nerves;
    • eye, salivary glands, and innervated skin (e.g., hair follicles) harbor virus
    • Salivary glands are important for animal dissemination

8

Rhabdovirus: Incubation period

  • Symptoms: 
  • Time depends on: 
  • Are there antibodies present?

  • *asymptomatic* (usually 3-8 wks) 
    • ranges from 1 week to 1 year
  • Time depends on:
    • dose (shorter with larger dose)
    • location of bite (shorter with bite closer to brain, e.g. neck or head) 
  • Low titer, virus in muscle, no antibody present at this time

9

Rhabdovirus: Prodrome

  • When does it occur?
    • Symptoms?
  • How long does it last?
    • Location and Serology?

  • Early after infection of brain, symptoms include:
    • nervousness, headache, anxiety, pain at bite site, fever, nausea
    • it is necessary to have a history of exposure in order to diagnose at this point
  • Lasts 2-10 days 
    • Virus present in the brain and often disseminated to other sites  
    • patients are usually antibody negative at this point

10

What is seen in the acute neurological phase of rabies?

  • High virus titer in brain and elsewhere
  • Antibody present in serum and CNS
  • Death is rapid in undeveloped countries (2-3 d) but longer with supportive care (3-10 d)

11

What is the difference between the 2 forms of the acute neurological phase of rabies?

  1. "furious" or fulminant (classic rabies) 
    • bizarre behavior
    • hallucinations
    • seizures
    • 'hydrophobia'
      • violent spasms of respiratory muscles triggered by drinking water
      • sight, sound, or mention of water can trigger it
    • gives way to paralysis, then either coma or sudden fatal cardiac or respiratory arrest
  2. paralytic or "dumb" rabies
    • ~20% of cases
    • ascending flaccid paralysis, leading to fatal paralysis of respiratory muscles

12

How is rabies initally diagnosed and how is it confirmed?

  • Initial
    • Neurologic symptoms in living persons with suspected exposure
  • Confirmation
    • ​Virus in CSF, saliva, or skin by PCR 
    • Antibodies present
      • By the time antibodies are detected, it is too late
    • Post mortem
      • PCR
      • direct fluorescence antibody (dFA)
      • virus cultivation
      • immunohistochemistry

13

What special microscopic marker can also be observed in rabies (50% of cases)?

Negri bodies

A image thumb
14

What is the cornerstone to prevention of rabies?

Immunization of domestic animals

15

What is the treatment for infected humans?

  • High risk individuals can be vaccinated 
    • Vets, field biologist, travelers to high-risk areas
  • Post-exposure Prophylaxis 
    • Almost always effective if incubation period is long enough, which is almost always the case 
    • Thus, although an exposure is not a medical emergency, PEP should be initiated as soon as possible after exposure

16

What is the prognosis of rabies?

Rabies is almost always fatal once symptoms appear