Rabies & Prions Flashcards
1
Q
How is the “Rabies” virus classified?
A
“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
Q
Rabies Virion Morphology
- Shape:
- What is under the membrane?
- Genome type:
- Proteins associated w/ genome:
A
-
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
Q
How does rhabdovirus replicate?
(long card….)
A
Prototype for (-) sense RNA viruses
-
envelope (G) can bind cell via several receptors:
- nicotinic acetylcholine receptor in muscle, ganglioside
- CD56 in neurons
- virus is endocytosed and envelope fuses at low pH w/ endosomal membranes to release nucleoprotein
- 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”
- Viral proteins are made from the mRNAs
- 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
- With protein and genomes present, viruses then assemble
- 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
Q
- How many serotypes exist for rhabdovirus?
- Which viral protein elicits neutralizing antibodies?
A
-
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
Q
entry is usually through a _____ or ____ ________ via a bite and introduction infected saliva
- How else can rhabdovirus be transmitted?
A
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
Q
- Where does rhabdovirus replicate during the incubation period?
- How long is the incubation period?
A
- virus replicates in muscle or connective tissue during “incubation” period
- Length: can be months
7
Q
Describe how rhabdovirus gets from the muscle to the brain and disseminates:
A
- 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
Q
Rhabdovirus: Incubation period
- Symptoms:
- Time depends on:
- Are there antibodies present?
A
- *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
Q
Rhabdovirus: Prodrome
- When does it occur?
- Symptoms?
- How long does it last?
- Location and Serology?
A
-
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
Q
What is seen in the acute neurological phase of rabies?
A
- 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
Q
What is the difference between the 2 forms of the acute neurological phase of rabies?
A
-
“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
-
paralytic or “dumb” rabies
- ~20% of cases
- ascending flaccid paralysis, leading to fatal paralysis of respiratory muscles
12
Q
How is rabies initally diagnosed and how is it confirmed?
A
-
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
Q
What special microscopic marker can also be observed in rabies (50% of cases)?
A
Negri bodies
14
Q
What is the cornerstone to prevention of rabies?
A
Immunization of domestic animals
15
Q
What is the treatment for infected humans?
A
- 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
