Virology - Ebola Flashcards
Outline the 2015 ebola epidemic.
- ~11, 000 deaths
- Most affected areas were Liberia, Sierra Leone, Guinea, and Nigera
Outline ebolavirus.
- Family Filoviridae: filamentous or thread-like viruses
- First identified in 1976
- Genus ebolavirus is divided into five species: Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SEBOV), Cote d’Ivoire ebolavirus (CIEBOV), Reston ebolavirus (REBOV), and Bundibugyo ebolavirus (BEBOV).
- Non-segmented, -ve sense RNA genome
- Filamentous morphology, ‘needle’ shape
- 80nm diameter, 800-14,000 nm length
- Helical, central core (ribonucleoprotein (RNP))
- Zoonotic virus, most likely reservoir is bats, although the species is unknown. Transfer to humans is likely through ingesting infected bushmeat.
Outline the ebolavirus outbreaks.
- Three initial African outbreaks (1970s)
- 1976: Sudan (E.sudan)
- 1976: Democratic Republic of the Congo (E.zaire)
- 1979: Sudan (E.sudan)
Most recent outbreaks:
- 2014 outbreak, West Africa
- Big outbreak in 2015, West Africa
Outline the proteins of ebolavirus.
- Nuclear protein (NP)
- Virion protein (VP) 35
- VP40
- Glycoprotein (GP)
- VP30
- VP24
- Polymerase protein (L)
RNP complex consists of NP, VP35, VP 30, L, and viral RNA
Surface consists of a cell-derived lipid envelope containing membrane-anchored glycoprotein (GP 1,2), which projects 10nm from the surface
Outline the replication of ebolavirus.
Most cell types, with the exception of lymphoid cells, can be infected by filoviruses.
- Binding and entry: mediated by the spike glycoprotein, GP<strong>1,2</strong>.<strong> </strong>GP1 is thought to interact with attachment factors and/or virus receptors, while GP2 modulates membrane fusion.
- Penetration: thought to be taken up by macropinocytosis in a glycoprotein-dependent manner into an endosome.
- Uncoating: the endosome is thought to degrade GP1 with a pH drop and proteases, leaving GP2 to fuse with the endosome membrane.
- Replication: transcription and translation are assumed to follow common mechanisms. Polymerase complex L and VP35 produce mRNA. Antigenomic RNA is produced which acts as a template for the -ve sense RNA.
- Assembly: requires VP40.
- The final virion then buds from the cell.
How is ebola transmitted?
Ebolavirus is present in high quantity in the blood, bodily fluids, and excreta of symptomatic patients. Therefore it can be spread through human-to-human contact through broken, or unprotected mucous membranes, direct/indirect contact with their bodily fluids, and through meat of an infected animal. People working in contaminated regions have to wear full body suits and masks.
- Unsterilised needles
- Airborne transmission (limited evidence in humans)
- Burial rituals of infected individual
- Handling of diseased primates
- Incubation of 2-21 days
- Not contagious in early stages, get progessively more hazardous with time
What are the symptoms of ebola?
Following an incubation period of 2-21 days there is a sudden onset of relatively non-specific symptoms including:
- fever/chills
- malaise
- myalgia (muscle pain)
- headache
- nausea
- vomitting
- sore throat
- diarrhoea
- abdominal and/or chest pain
In fatal cases, disease progression may include other signs, which is where the name ‘haemorrhagic fever’ arises:
- haemorrhage
- bruising
- bleeding from mucous membranes
- haematuria
- Vomitting
Case fatality depends on the species: ZEBOV (60-90%), MARV (25-90%), SEBOV (50-60%), BEBOV (25%), CIEBOV (0%), and REBOV (0%). Non-fatal cases resolve in 6-11 days.
Outline the pathogenesis of ebolavirus.
- Initial target for replication is the macrophages/monocytes (results in systemic chemiokines, cytokines and other mediators being released) and dendritic cells (impairs function, can’t release pro-inflammatory molecules or IFN).
- Increased vascular permeability, disseminated intravascular coagulation (DIC) and impaired immune response.
- Infection cannot be controlled due to IFN suppression.
- Move from initial cells to lymph nodes, liver and spleen (primary sites).
- Move to adrenal cortex, and stay in liver, where extensive virus replication and necrosis occurs (secondary sites).
- Widespread necrosis of parenchyme cells.
- Poorly maintained fluid distribution (liver and kidney) lead to systemic oedema disseminated intravascular dissemination (DIC).
How is ebola diagnosed?
- As outbreaks occur sporadically, diagnosis is usually done based on clinical symptoms. Single cases can be misdiagnosed based on diseases with similar symptoms, e.g. malaria.
- When possible, international reference laboratories should be involved in sample collection, storage, and transport, especially in non-endemic countries.
- Currently the most frequently used method to identify filovirus infections is RT-PCR on blood samples. Nucleic acid can be detected in blood as early as 3 days post-onset of symptoms. Rapid and specific.
- Viral antigen detection is performed using ELISA-based methods. Typically this is performed to confirm results from RT-PCR.
Outline how ebola is treated.
- There is currently no vaccine, but over 15 are in development and clinical trials (In North America, Russia, Europe, and China)
- These include the two most advanced – VSB-EBOV and ChAd3-ZEBOV.
- Only supportive care, which is directed towards the maintenance of effective blood volume and electrolyte balance.
- Hypovolemia and sepsis physiology (IV fluid resuscitation, haemodynamic support)
- Electrolyte repletion
- Symptomatic management of fever and GI symptoms, avoid NSAIDs
- Multisystem organ failure may require:
- Oxygenation and medical intervention
- Correction of severe coagulopathy
- Renal replacement therapy
These facilities however are not available to a lot of the people who need them in the epidemic regions.
Name the main proteins in ebola.
