Just Why Is Ebola virus so Deadly?

Ebolavirus, particularly the species Zaire ebolavirus, is the causative agent of Ebola virus disease, which is characterised by is extremely high mortality. There have been a number of outbreaks in recorded history, but none more severe than the one currently going on in Western Africa, which is threatening to reach epidemic proportions. But just why is the virus so feared, why is it so deadly?

Taxonomy


All five species included in the genus Ebola virus are members of the Filoviridae family. This name denotes the fact that all members of this family produce virions that are filamentous in nature. Though generally tubular, these viruses can take on slightly different morphologies, including loops, a U, a 6, a circle or branched; though it is unclear whether laboratory techniques such as centrifugation are the cause of these observed morphologies.  Further up the taxnonomical tree, Ebola viruses belong to the order Mononegavirales, which also includes the viruses that cause Measles and Rabies. The members of this order can be quite different to each other, but are grouped together due to the fact they all contain negative sense, single-stranded RNA.

The Genome


Each virion contains a single molecule of single-stranded, negative sense RNA. Just like DNA, this form of RNA cannot be directly translated into viral proteins. Instead, the virus carries with it its own RNA-dependent RNA polymerase, which converts the negative-sense genome into a positive-sense one. This form RNA is the same as that which is produced by our own cells the process of protein synthesis. As such, from this point the virus can use host enzymes to continue its life cycle.

genome

The viral genome (shown above) codes for seven proteins: NP (nucleoprotein), VP35 and VP30 (both of which aid the RNA polymerase), GP (surface glycoproteins), VP24 and L (the RNA polymerase). Interestingly, the RNA polymerase will only transcribe one gene at a time before attenuating and falling off. Therefore, each gene is produced independently of the others – transcription produces polycystronic RNA. Therefore, since the RNA polymerase travels in a 3′ -> 5′ direction, more NP is produced than VP35/VP40, of which more is produced than GP and so on. This is thought to occur as a way of allowing the virus to control its life cycle, as a certain cumulative concentration of the final gene, VP24, is believed to stop the replication process and trigger the process of creating progeny virions.

The Virulence Factors


 

Every pathogen produces virulence factors, molecules that allow them continue their life cycle in the host more efficiently. This can include colonisation of the niche of their host that they inhabit, escape from and inhibition of the host immune system, entry into and exit out of cells and sapping nutrition from the host. It is the presence of these virulence factors that contribute to how deadly a virus is. Ebola virus contains 4 main virulence factors, which can be grouped into 3 classifications:

virulence1

It is clear to see that Ebola’s main virulence factors all focus on reducing the impact of the host immune system. VP24 and VP35 prevent the action of Type I and III interferons, which are produced in all cells upon the detection of a virus. Though it is unclear to what extent the apoptosis of bystander lymphocytes occurs, but what is known is that it severely dents the level and quality of the immune response to virally infected cells. The increased production of TRAIL and circulatory Fas indicates both the intrinsic and extrinsic paths of apoptosis are triggered, meaning the process is extremely efficient. Glycoproteins play a dual role in acting as virulence factors. They both act as decoys to prevent circulating antibodies from performing their functions on virally infected cells and they replace the normal glycoproteins on the surface of the cell. This means that it is harder for ther normal cells, such as those of the immune system, to recognise the infected cell.

As is often the case with the most infamous of viruses, Ebola has over time created the near-perfect characteristics to infect and survive in human populations; be that the way it enters cells, carries out its life cycle once it has entered them and how it protects itself from the immune system. The one thing it is yet to perfect is the extent of disease that it causes. The most proficient pathogens are those that have the infectivity and survival characteristics of Ebola but do not cause widespread death of infected individuals, because when the host dies, the pathogen dies. However, with the current 2014 outbreak, there are concerns that this balance has been evolutionarily addressed, as this outbreak has both by far the most infected people and one of the lowest mortalities associated with it.

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