Rabies, Prion diseases, and Herpes - McNally Flashcards
What family does the rabies virus belong to?
What genus?
Family: Rhabdovirus
Genus: Lyssavirus
[I think of a rabid“rhabbit” named Alyssa.]
What shape is the rabies virus?
Rod or bullet shaped (rhabdo means rod)
What are the three main layers of the rabies virus that encapsulate the viral genome?
From external to internal:
Viral envelope with glycoproteins
Membrane with M protein
Nucleocapsid layer
What genome type does the rabies virus have? Be specific.
Antisense, single-stranded RNA
What are the five genes of the rabies genome?
Which part of the virus does each encode for?
G, M, NS, L, and N
- G: Glycoproteins of the envelope
- M: M protein of the membrane
- N: Nucleocapsid protein which coats the RNA
- **NS & L: **Make up the viral (RNA dependent) RNA polymerase
The envelope (G) of the rabies virus can bind host cells via several host receptors. Name three and what cell types they are found on.
Muscle cells: Nicotinic ACh receptor
Neurons: Ganglioside and CD56
Following endocytosis, how does the rabies virus get its genome into the cytosol?
Viral envelope fuses with host endosomal membrane (again mediated by glycoprotein G) at low pH, releasing the viral nucleoprotein.
Once its nucleoprotein is within the cytosol, describe how the rabies virus replicates itself.
- First, the viral RNAP produces mRNAs from the (-)RNA.
- The host’s ribosomes produce viral proteins from the viral mRNA.
- Eventually, the viral RNAP switches from making mRNA (for protein) to making full-length (+)RNA.
- The (+)RNA is used as a template to produce full-length (-)RNA copies of the viral genome
- The proteins and genome then assemble. G protein inserts into the host membrane. The other proteins coalesce to assemble new virions, which bud off the cell and acquire an envelope in the process.
What is unique about the budding of nascent rabies virions from host cells?
Budding of rhabdoviruses typically kill the host cell, but not the rabies virus.
What protein of the rabies virus is immunogenic and allows for vaccine production?
G protein (makes sense - it’s on the outside of the virion)
[Note: As you might expect, the natural timeline of antibody production is not protective against the virus, necessitating the vaccine.]
- If a patient presents with an animal bite from an animal they did not see (it was dark, they fled without getting a good look at it, etc.), and you detemined they had rabies, how could you determine the type of animal the rabies came from?
- How many serotypes of the virus are there?
- mAbs or genome sequencing would reveal small genetic variations of the virus that differ between animal host species.
- Despite these small genetic differences, there is only one true serotype of the rabies virus
By what means is the rabies virus typically spread?
Saliva of the infected animal, via a wound or skin abrasion.
There has been one case of aerosol infection in cave explorers and rare reports of infection via cornea or even organ transplants.
Describe the incubation period of the rabies virus.
Where is the virus?
How long is the incubation period?
Why is the incubation period important clinically?
Virus replicated in muscle or connective tissue around the site of injury.
The incubation period is typically 3-8 weeks long, but can be as short as one week or as long as a year. The disease is almost always lethal once it reaches the CNS. Thus, intervention during the incubation period is critical!
How does the rabies virus reach the CNS? How quickly can the virus “move”?
The virus enters peripheral nerves at the muscle and is carried through axons to the CNS. The brain is rapidly infected. Movement is 8-20mm/day.
Once the rabies virus has replicated throughout the CNS, what other sites can it disseminate to?
- Eyes (recall: infection possible via cornea transplants)
- Salivary glands (duh)
- Innervated skin (e.g. hair follicles)
What factors influence the length of the rabies virus incubation period?
- Shorter with larger viral dose
- Shorter with bite location that is closer to the brain (head or neck)
Describe the timing and features of the prodrome of rabies infection.
- Early after infection of brain
- Lasts 2-10 days.
- Virus typically already disseminated to other sites (can be detected in skin biopsies or saliva)
- Pt is usually antibody negative at this point
- Sxs include nervousness, headache, anxiety, pain at bite site, fever, nausea. Progresses to myoclonus, slurred speech, and “tingling”.
Describe the features and timing of the acute neurological phase of rabies infection.
What two forms can the disease progression take? Describe each.
- High virus titer in brain and elsewhere.
- Antibody present in serum and CNS.
- Death is rapid (2-3 days without supportive care, 3-10 days with)
Forms:
- Furious or fulminant rabies (classic): hallucinations, seizures, hydrophobia. Fury gives way to paralysis, then coma or sudden cardiac or respiratory arrest
- **Paralytic **or dumb rabies: ~20% of cases. Ascending flaccid paralysis. Eventual fatal paralysis of respiratory muscles.
Describe what hydrophobia actually presents as in rabies patients.
- Violent spasms of respiratory muscles triggered by drinking water
- Can also be triggered by the sight, sound, or even mention of water.
How does the pathology of rabies appear histologically?
Little pathology despite the devastating effects.
Negri bodies (foci of virus production) can be seen in some cases.
Diagnoses currently is via antibody tests.
There were five documented cases of clinical rabies survival prior to the succesful use of the Milwaukee Protocol. Why is the Milwaukee case so important then?
It was the first case of survival where NO immunotherapy intervention was initiated; aka the patient’s immune system eradicated the virus on its own. In the other five cases, all the patients were either vaccinated or received post-exposure immunotherapy.
