Marburg and Ebola Flashcards
What are Marburg and Ebola?
- filoviruses
- ss negative sense RNA genomes
- enveloped
Describe the general genome structure of Ebola + Marburg viruses
- 7 genes
- NP nuclear capsid
- VP35, VP40
- GP glycoprotein
- VP30, VP24
- Large gene - RNA dependent RNA polymerase
What are the roles of the VP30, 40, 24 and 35?
VP30 - minor nucleoprotein
VP40 - matrix protein
VP24 + 25 interfere with innate immune responses
(VP24 is also required to assemble virus particles in vitro)
Describe typical infection with Ebola virus
- sudden onset of fever, headache etc
- deteriorates into nausea, vomiting tinittus blindness
- hiccups due to bleeding around the lungs
- haemorrhagic symptoms - spontaneous leakage of blood from the vessels
- causes patients to bleed uncontrollably so intravenous treatment cant be given
What causes death from Ebola and Marburg viruses?
- extreme blood loss, shock and death
- 1-2 weeks after symptoms start
- fatality rates vary from 30% in Marburg to up to 90% in ebola zaire
How do Ebola and Marburg virus spread?
- close contact
- droplets, sputum, blood and semen
- this limits the viruses ability to cause global pandemics as it is easier to control the spread than respiratory disease
Where is Ebola theorised to have come from?
- natrual host it co-exists with
- most likely bats
- other animals such as monkeys, rats also die of disease so can’t be them
What is special about the Ebola reston strain?
- from Asia rather than Africa
- killed monkeys but was asymptomatic in humans
- seroconversion in those exposed to infected monkeys shows it was entering humans
- many gene changes such as in the glycoprotein
What is sGP of Ebola?
- a second form of the glycoprotein that doesnt attach to the virus but is excreted and present in the blood
- subverts the immune response by misdirecting Ab responses to non-neutralising sGP
How are sGP and GP expressed in Ebola virus?
- encoded in a single transcript
- no RNA pol editing in 70% of cases allows sGP to be transcribed
- 25% of the time, the polymerase adds an extra A, changing the reading frame and allowing GP to be transcribed instead
What is thought to be the cause of haemorrhagic symptoms in Ebola virus?
- GP is cleaved by intracellular proteases into GP1 and GP2
- GP1 is involved in attachment and 2 acts as a membrane anchor that acts to increase vascular permeability
- evidence to show that attachment of GP to endothelial cells triggers cell death by vascular permeability
- acts as the pathogenic determinant - reston could do this in monkeys but not in humans
How does Ebola virus challenge the innate immune response?
- VP24 and 35 most important
- can block signalling for example prevent STAT proteins from entering the nucleus to trigger INF responsive genes
- can stop IFITMs from inhibiting virus entry
- GP2 interacts with tetherin to stop it from inhibiting virus exit
How does the immune response appear to differ in the few that overcome Ebola virus and in those that die?
- survivors have a good humoral and cell mediated response and build immunity to subsequent infection
- neutralising Abs and other signs of an immune response are hard to find in those that die of infection
What parts of the immune response seems important in survival of Ebola infection?
- early and effective antibody response
- effective inflammatory response in early stages
- appropriate cell mediated response
What are most vaccines against Ebola focused on?
- antibody response to GP
- humanised neutralising antibody cocktails also focus on this target
