Rhabdoviruses Flashcards
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Describe the general properties and structure of Rhabdoviruses.
☛ typically bullet shaped or baciliform (rod-like)
☛ the virus is enveloped
☛ the envelope is studded with glycoprotein spikes (G protein) that are crucial for attaching to and entering host cells.
☛ inside the envelope, the viral RNA is tightly bound to nucleoprotein (N protein) forming a helical nucleocapsid.
☛ matrix protein (M): The matrix protein lies between the envelope and the nucleocapsid, providing structural integrity and playing a role in virus assembly and budding.
Briefly discuss the genome of Rhabdoviruses and the important proteins it encodes for.
☛ RNA Type: The genome is a single-stranded, negative-sense RNA (ssRNA) molecule.
☛ The genome typically encodes five main proteins in the following order: N (nucleoprotein), P (phosphoprotein), M (matrix protein), G (glycoprotein), and L (large protein, which functions as the RNA - dependent RNA polymerase.)
List three genera of Rhabdoviruses that infect humans.
⚚ Lyssavirus [Rabies, Duvenhage, Mokola]
⚚ Vesiculovirus [Vesicular stomatitis virus (Indiana), Chandipura]
⚚ Tibrovirus [Congo, Alphaekpoma and Betaekpoma tibroviruses]
Rabies virus
(a) Family
(b) Genus
(c) Baltimore classification
(a) Rhabdoviridae
(b) Lyssavirus
(c) Baltimore group V (-ssRNA genome)
How is rabies transmitted?
✓ It is usually transmitted by being bitten by an infected animal. In most parts of the world, the principle reservoir for urban rabies is dogs.
✓ It may also be transmitted if the virus comes into contact with mucosal surfaces such as the mouth and eyes.
✓ organ transplants from infected donors
[2-minute video]: Rabid animal 1
[2-minute video]: Rabid animal 2
Discuss the pathogenesis of rabies.
☛ The rabies virus enters the body through the bite or scratch of an infected animal, or through contact with infected saliva on mucous membranes or broken skin.
☛ The virus initially replicates in muscle cells at the site of entry and invades peripheral nerve fibres at the neuromuscular junction [by binding to acetylcholine receptors at neuromuscular junctions].
☛ It then travels along the nerves towards the central nervous system using retrograde axoplasmic transport.
☛ Once in the CNS, the virus rapidly replicates, causing inflammation and damage to nerve cells [causes encephalitis].
☛ The virus spreads centrifugally from the CNS to various tissues, including the salivary glands.
☛ It is then shed in the saliva, completing the infection cycle and enabling transmission to new hosts.
Further notes:
Axonal transport recap
⚡ Anterograde axonal transport
Direction: Moves materials from the cell body (soma) to the axon terminal.
Motor protein: Kinesin.
Cargo: Includes synaptic vesicles, mitochondria, proteins, and lipids.
Speed: can be fast (50-400 mm/day) or slow (less than 8 mm/day) depending on the cargo.
⚡ Retrograde axonal transport
Direction: Moves materials from the axon terminal back to the cell body.
Motor Protein: Dynein.
Cargo: Includes endosomes, autophagosomes, and signaling endosomes.
Function: Helps in recycling cellular components and conveying signals from the axon terminal to the cell body
What are the effects of the rabies virus in the CNS.
➤ abnormalities in neurotransmitter release and secretion [GABA, ACh, serotonin]
➤ dysfunction in potassium and sodium channels, causing misfiring
➤ increased nitric oxide production
➤ disruption of neuronal cytoskeleton
➤ Negri bodies; neuronal cytoplasmic inclusion bodies
Negri bodies: [Slide 1] [Slide 2] [Slide 3] [Diagram 1] [Diagram 2]
Discuss immune response in relation to rabies infection.
➤ An immune response is not detectable up to 7-10 days after infection.
➤ There is limited inflammatory response in the CNS. [The rabies virus has evolved mechanisms to evade the host’s immune system, particularly within the central nervous system (CNS). This evasion results in a limited inflammatory response, allowing the virus to replicate and spread with minimal interference from the host’s immune defenses.]
➤ Rabies interferes with Interferon response (Phosphoprotein).
➤ Suppression of apoptosis of infected cells. This allows the virus to persist and replicate within these cells without being destroyed by the host’s immune system.
➤ It induces: (1) Mononuclear cell infiltration, (2) Lymphocytic perivascular cuffing (Babes nodules), (3) Lymphocytic foci
Further notes:
Lymphocytic perivascular cuffing (Babes nodules): This is a histopathological feature where lymphocytes accumulate around blood vessels in the brain. These nodules are indicative of an immune response to the infection within the CNS. [Slide 1] [Slide 2] [Slide 3]
Lymphocytic foci: These are small clusters of lymphocytes found in infected tissues, representing localized immune responses attempting to contain the virus. [Slide 4]
Discuss the clinical presentation of rabies infection. [incubation period, prodrome, acute neurologic phase etc.]
➤ Incubation period: 20 - 90 days [may even take years]. It depends on concentration of the virus, inoculation site and density of innervation.
➤ Prodrome: 2 - 10 days.
Characterized by: fever, anorexia, headache, pain/numbness at the bite site.
➤ Acute neurologic phase: 2 - 7 days
Furious rabies: hyperactive, hydrophobia, aerophobia, confusion, hallucinations, autonomic dysfunction [increased salivation/lacrimation], may progress to death or paralysis.
[1-minute video]: Patient with Hydrophobia
Paralytic rabies: patient is quiet and calm, headache and fever are prominent, flaccid paralysis
➤ Coma/Death: 1 - 14 days
Further notes:
In the context of rabies infection, the prodrome is the initial phase where early symptoms appear before the more severe neurological symptoms set in.
Briefly discuss the diagnosis of rabies.
📝 done through history and clinical presentation
📝 there is no reliable test before the onset of symptoms
📝 once symptoms begin, the virus may be found in samples of saliva, brain tissue, skin and urine. Techniques such as serology, PCT and microscopy may be used to confirm diagnosis.
Discuss the management of rabies.
📝Clean bite site with soap and water then disinfect with antiseptic.
📝Administer post-exposure prophylaxis. PEP is 100% effective if given before onset of symptoms. It is usually given in two forms: Rabies Vaccine and Human Rabies Immunoglobulin.
📝 Antibiotic treatment and tetanus prophylaxis.
📝 If symptomatic, give supportive care. [Don’t let them dehydrate/starve to death.]
📝Nearly always fatal.
Discuss rabies vaccines.
📝 Rabies vaccines are inactivated vaccines.
📝 They elicit antibodies in 7 - 10 days.
📝 A pre-exposure regimen is recommended for people at higher risk of rabies exposure, such as veterinarians. It involves a series of three doses given on days 0, 7 and 21 or 28.
📝 Post-exposure prophylaxis is given to people who have been exposed to the virus. There is a 5 dose regimen [0, 3, 7, 21, 28], 3 dose regimen [0, 7, 21] and a two-site intradermal method: day 0, 3, 7 and 28 (lower dose of 0.1ml).
Discuss prevention measures against rabies.
📝 Vaccination of humans at risk of infection
📝 Vaccination of dogs/pets
📝 PEP
📝 Public health education
📝 Surveillance
📝 Avoid contact with animals that are sick or showing unusual behavior.
