rabies and lyssavirus Flashcards
1
Q
stages of rabies
A
- Early ○ Bite ○ No symptoms (20-90 days) - Symptoms begin ○ Kills ~ 100% once symptoms begin ○ Sensation at original bite site ○ Flu0like symptoms - Clinical (furious (80%), paralytic (20%)) ○ Fever, mouth salivates, convulsions ○ Hydrophobia (unique to rabies) § Fear of water § Can't even drink water ○ Hallucinations ○ Hypersexual behaviour ○ Moments of clarity Coma, death
2
Q
Vaccine and treatment
A
- Vaccine developed by Louis Pasteur and Pierre Roux
○ Weaken a virulent rabies virus by aging and drying spinal cords of rabies-infected rabbits
○ Tested on 9 year old rabies patient- Vaccines improved (inactivated)
○ Recombinant vaccines (g protein) - At risk individuals
- Can be applied post-exposure (before symptoms)
Rabies immunoglobulin, 5 vaccine treatment
- Vaccines improved (inactivated)
3
Q
Still a problem
A
- > 55,000 deaths a year
- Under reported, under-served, poorly resourced regions, rural
- Vaccine expensive; multiple courses
- Zoonotic - almost all warm-blooded animals can be infected
- > 99% human cases come from dogs
- Almost impossible to completely eliminated due to so many wild-life reservoirs
- Control: vaccination of dogs, pets
○ Wild-life oral baiting (herd immunity)
Humans are a dead-end host (no human to human transmission)
4
Q
is rabies caused exclusively by the rabies virus
A
no, other viruses can cause rabies. e.g. Lyssavirus
5
Q
Does Australia have rabies
A
- Australian Bar Lyssavirus virus (ABLV)
- Very similar to rabies virus
- Zoonotic - flying foxes, bats
- Treatment
○ Same for rabies, rabies immunoglobulin and rabies vaccine protects against lyssavirus - Prevention
Avoid handling bats
6
Q
Rabies infection of the host
A
- Animal bite or scratch (virus in saliva)
- Infects muscle (replicates), transmitted to peripheral nerves, then central nervous system
- Virus particles transport in along neuronal axons (retrograde = towards cell body) in vesicles using microtubules
- When at neuronal cell body, released from vesicle, replicate, assemble new virus particles, then infect next neuron
- Travels up spinal cord, leading to brain, causes encephalitis
Spreads to other organs (e.g. salivary glands)
7
Q
In the neuron
A
- Virus endocytosed into the neuron from muscle
- Gets a ride on the microtubules to cell body
- Once in cell body gets released out of endosome and can start replicating
- Transports to the trans-synaptic spread
Goes to the next neuron
8
Q
rabies process efficacy
A
Slow process (depending on where bitten) - allows time to vaccinate
- If bitten on foot has to travel a lot further than if bitten on the face
Very little sign of damage to neurons (how does it kill?)
- Very stealthy - very little cytopathic effect
- Inhibits apoptosis
Immunosuppressive strategies (immune evasion)
9
Q
Lyssaviruses: the stats
A
- RNA ○ mutate quickly (no-proofreading), small genome, must make its own RNA polymerase - Single strand and negative-sense ○ Must bring RNA polymerase - One (monopartite) ○ One molecule, non segmented - Order - mononegaviruses ○ Rabies (rhabdoviridae) ○ Ebola (Filoviridae) ○ Nipah (Paramyxoviridae) Envelope - YES
10
Q
Rabies virion/ particle
A
- Enveloped
- Helical (wrapped up by M protein)
- All 5 proteins in particle (N, P, M, G, L)
- N binds and covers (encapsulates) RNA genome (nucleoprotein) forming a ribonucleoprotein
○ RNA + protein
G on surface (spikes)
11
Q
Lyssavirus Genome
A
- ~11-12 kbp long (average RNA virus long)
- 5 genes as said above
- L brings RNA-dependant RNA polymerase to make mRNA
- Then can make viral proteins (N, P, M, G, L)
mRNA made by host ribosome (host makes proteins)
12
Q
Attachment and entry
A
- The particle itself has the glycoprotein
○ Binds to the receptor of the host cell- Induces endocytosis
- Clathrin-coated pits form allowing virus into cell but enclosed in endosome
- Endosome hooks onto microtubules
- Transported to cell body
○ As the endosomes head towards the cell body the inside of the virus becomes more acidic
○ Inducing a conformational change
○ The glycoprotein fuses in, brings the membrane from the virus and the membrane from the virus together so they can merge
○ Then release out the nucleocapsid
Contains L protein, M protein and P protein
13
Q
Synthesis
A
- Nucleocapsid is a ribonucleoprotein complex
○ RNA strand + N, P and L proteins- Nucleocapsid released into cytoplasm
- Transcription - make viral mRNA
- Translation - make viral proteins
- Replication - -ve RNA genome -> +ve RNA antigenome
Used as a template to make more -ve RNA genome
14
Q
Transcription
A
- We need the RNA encapsidated by N protein
- We need the P protein to act as the intermediate
○ Binding to L protein and N protein
○ Brings them together
○ So polymerase can start - The P&L complex starts at 3’ end
- Transcribing across using a stop start mechanism
○ There’s a signal sequence in the RNA telling the complex to disengage and re-engage and make next gene - Sometimes the PL complex falls off as it moves across the genome
○ Therefore we will always have more of the first proteins (N>P>M>G>L)
Called the transcriptional gradient - as sometimes the complex fails to re-engage
- We need the P protein to act as the intermediate
15
Q
Translation
A
- Uses host ribosomes
Has transcriptional gradient of course
