Virology- Rhabdoviruses | Quick Revision Notes for NEET-PG

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Rabies virus

Rapidly progressive acute infectious disease of CNS  in human and other animals

It has a unique morphology

  1. Bullet shaped
  2. 10nm long spikes of glycoprotein-G embedded in the Lipid envelope. This envelope is lined internally with a layer of matrix proteins
  3. Helical nucleocapsid with  -sense ssRNA

Rabies only has a single serotype

Animal susceptibility to host viruses(in decreasing order)

Foxes, jackals, wolves and cotton rats> rabbits cattle cats hamsters raccoons and bats>goat sheep horses dogs>opossums(most susceptible to least susceptible)

Street stains are isolated strains kept in the lab that mimics the wild viruses. Shows long Ip and produce intracytoplasmic inclusion bodies. When street viruses are passed through the serial intracerebral passage in rabbits, they lose certain properties and then come to be known as fixed strains.

Pathogenesis

  1. Rabies virus is transmitted to the virus through infected animals(dog-MC)
  2. Migrating fruit-eating bats are the MC bats that transmit rabies in America.
  3. Other methods of transmission- corneal transplantation/inhalation of virus-containing aerosols generated from infected bats

Street viruses

Fixed viruses

Freshly prepared

Isolated after serial intracerebral

The passage in rats and cell lines

Produce Negri bodies

Do not produce the Negri bodies

Affect the salivary gland

Do not affect the salivary gland

Pathogenic

Non- pathogenic

IP- 1-3 months

IP- 4-6 days

Produce disease

Used for vaccine

Spread of virus

  1. Virus starts replicating locally in the muscles and CT———>virus binds to Ach R on the NMJ and enters the peripheral neurons———–>virus spreads centripetally along the never via the retrograde axonal transport———> reaches the dorsal root ganglion os spinal cord———>ascends upwards towards the CNS——-> reaches CNS—–> rapidly disseminated in the various parts of CNS (MC- hippocampus/cerebellum, etc)-——->from CNS virus spreads along sensory and autonomic nerves to salivary glands/pancreas/kidney/heart/ and cornea———> virus is shed in the saliva of rabid animals and this act as a source of infection for other animals.

Clinical manifestations

Ip- 1 week to 19 years(depending upon the site of inoculation)

3 phases

Short prodromal phase

Acute neurologic phase

Coma and death

Last for 2-10 days

Last for 2-7 days

Death within 14 days

Characterized by non-specific symptoms live fever, malaise, anorexia, nausea, vomiting, etc

Encephalitic type(80% of cases)-

  1. Hyperexcitability- anxiety, agitation, bizarre behavior, and hallucinations
  2. Lucid interval-follows period of hyperexcitability
  3. Autonomic dysfunction- ^lacrimation ^salivation ^perspiration etc
  4. Hydrophobia as the act of swallowing precipitates painful involuntary spasm of laryngeal, pharyngeal and respiratory muscles

Paralytic type(20% of cases)

  1. Begins with flaccid paralysis of a bitten limb, progressing to quadriparesis and facial paralysis

Recovery and survival are extremely rare

Lab Dx

  1. Antigen detection by Direct If
  2. the best specimen is hair follicle of nape or neck
  3. Corneal impression smears can be used
  4. Intracerebral inoculation onto the suckling mice——-> cause encephalitis and death—–> brain biopsies are examined——->examined for the presence of rabies antigen and Negri bodies
  5. Inoculation of the clinical specimen into the BHK cell line/ mouse neuroblastoma cell line—–>viral growth is detected by direct IF using fluorescent tagged monoclonal antibody.
  6. Antibody detection in CSF by CFT, HAI, neutralization test
  7. Viral RNA detection via RT- PCR
  8. Negri bodies detection for postmortem Dx – these are intracytoplasmic spherical to oval eosinophilic inclusions with basophilic granules commonly observed in Purkinje cells of the cerebellum and pyramidal neurons of the hippocampus (stained with H and E)

Prevention

  1. All bite wounds and scratches should be cleaned with soap and water
  2. Antiseptics like povidone iodine and alcohol should be used
  3. Devitalized tissue should be debrided
  4. Do not suture
  5. Administration of Human rabies immunoglobins(passive immunity) at the site of exposure in a dose of 20 IU/kg. It is devoid of any side effects
  6. Active immunization can be done by administering neural /non-neural vaccines
  7. Neural vaccines are derived from neural tissue of animals infected with fixed rabies virus.it is less immunogenic and encephalitogenic.
  8. Non-neural vaccines are cell line derived or recombinant glycoproteins
  9. Cell line derived vaccines use Vero cell line(purified vero cell vaccine), WI-38(Human diploid cell vaccine) or chicken fibroblast cell line(purified chick embryo cell vaccine).
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