Rabies Flashcards
Go over the rabies taxonomy.
Order: Mononegavirales
Family: Rhabdoviridae
Genus: Lyssavirus
Go over the rabies structure.
Unique bullet-shaped appearance
Surface covered with glycoprotein (G) spikes (trimers)
Matrix (M) protein inside links nucleocapsid with envelope
Nucleocapsid = viral RNA bound to the N protein (nucleocapsid also termed ribonucleoprotein)
Viral RNA dependent RNA polymerase (RdRp) proteins L and P bound to nucleocapsid
Go through the lifecycle of rabies virus.
- Attachment— glycoprotein G binds to nicotinic acetylcholine receptors (can also use alternate receptors)
- Entry/Uncoating—low pH dependent fusion with endosomal membranes
- Acidic interior of the endosome allows the viral
nucleocapsid (N + RNA) to escape into the cytoplasm - M protein dissociates from the nucleocapsid
- Acidic interior of the endosome allows the viral
- Transcription of Viral Genes
- L (RNA dependent RNA polymerase) begins to transcribe the viral genome
- Viral Protein Synthesis
- viral mRNAs translated by host cell ribosomes
- Genome replication
Full-length + ssRNA copies (antigenomes) made from – strands genomes
- Anti-genomes (+) RNA serve as templates for progeny
(-ssRNA) genomes which will be packaged into the viral particle - Virus Assembly/Exit
- As soon as -ssRNAs, N, M, P, L proteins have accumulated within infected cells, assembly occurs
- The mature infectious particle buds through host cell plasma membrane
Go through rabies pathogenesis
Entry through break in skin
Virus replicates in the muscle cells surrounding the wound
Virus attaches to nicotinic acid receptors of the peripheral nerve cells of the neuromuscular junction
Virus journeys within axons of nerves
It may take weeks before the virus reaches the spinal cord motor neurons of the CNS
This is why post-exposure vaccination is possible
Antibodies prevent the spread of the virus to the CNS, stopping the disease
What are the clinical signs and symptoms of rabies?
2 forms of human rabies
- Furious (encephalitic)
- Paralytic (or dumb)
With either form, incubation period varies
4 days to 6 years (rare)
Average 18-21 days post-exposure
Death occurs on average 18 days after onset of symptoms
What are the phases of rabies?
Prodromal Phase -> Acute Neurologiical -> Coma/Death
Furious rabies and paralytic rabies are different types of symptoms that can be experienced during the acute neurologic stage
What are the differences in secondary symptoms for furious rabies and paralytic rabies?
Furous Rabies:
- Agitation
- Hallucinations
- Bizarre behavior
- Biting
Paralytic Rabies:
- Weakness and ascending paralysis are only symptoms
How is rabies diagnosed in humans?
Several routine antemortem tests available in the U.S.
Virus isolation
- RT-PCR to detect viral RNA most sensitive antemortem test
Human Postmortem direct fluorescent antibody (dFA) tests
- Performed on brain of victim
- Brain tissue sections stained w/ antibodies linked to a fluorescent marker
- Any rabies present will be a fluorescent signal
- Gold standard for rabies diagnosis
What are the classical pathological sign of rabies in the brain?
Classical pathological lesions called Negri Bodies
If post exposure prophylaxis doesn’t occur what are the chances of survival?
Without post-exposure prophylaxis, rabies almost always fatal after secondary symptoms develop (virus in brain)
How many strains of rabies are there?
6 strains of rabies present in wild animals
- each strain of rabies has preference for type of animal it infects
- doesn’t mean it can’t cause infection in other species of animal
What animals are reservoirs for rabies in the U.S.?
Three terrestrial wild animals in the U.S. That are reservoirs for rabies
- Racoon: East Coast
- Skunk: Midwest
- Fox: Southwest
Where do most human cases of rabies originate from?
Bat bites
From the Taming Rabies Paper:
Who made the first rabies vaccine?
Louis Pasteur
From the Taming Rabies Paper:
What was the goal set by the WHO?
Reduce number of rabies deaths by 2030
Strategy: vaccinate dogs; vaccinate ppl who are at high risk
