The 2014 West African Ebola virus outbreak made for a tragic loss of life and caused widespread social disruption. The epidemic started in late December of 2013 in Guinea presumably due to the ingestion of fruit bat meat, which has consistently proven to be a reservoir for the Ebola virus.1 From there, the virus spread to neighboring countries and cases were seen as far as the U.S., Spain, the U.K., and Italy, sparking panic in the Western world.2 The epidemic was the worst Ebola outbreak in recorded history and challenged the finest laboratory researchers and public health workers.3 An effective epidemic response has the potential to save many lives and in the case of the 2014 Ebola outbreak, we witnessed a successful response plan lying delicately at the intersection of science, culture, and health. On a macro scale, an epidemic response plan must address the spread of the disease as well as the mobilization of healthcare workers and other logistics. On a micro scale, researchers must delve into the molecular world and uncover distinguishing qualities of these microorganisms in the hopes of creating drug therapies and other treatments.

The first reported case of the Ebola virus in humans was in the late 1970’s in Zaire, which is now known as the Democratic Republic of Congo (DRC).4 This epidemic claimed close to 300 lives in the DRC, whereas the 2014 outbreak claimed around 11,000 lives with about a 40% fatality rate after infection.3,5 As the death count grew, so did the world’s interest in the virus. Subsequently, research to combat the virus accelerated dramatically. It was discovered that there are 5 different species of the Ebola virus: the Zaire, Sudan, Cote D’Ivoire, Bundibugyo, and Reston Ebola viruses,5 with Zaire being the strain responsible for the 2014 epidemic.2

Epidemic response on a social, or macro, level is a complicated process that is greatly limited by time, geography, and culture. It wasn’t until about six months after the initial infection in Guinea during the 2014 outbreak that many global health organizations, such as the WHO, UN, Partners in Health, Doctors Without Borders, and Red Cross among many others, became heavily involved in the Ebola outbreak.6 Some of the first courses of action involved setting up isolation facilities, deployment of trained healthcare workers to high-risk locations, distribution of medical supplies, and coordinated inter-governmental communication.7

 

The origin of pathogenesis begins with one’s exposure to the virus. Specifically, this means viral entry into the body via mucosal surfaces, skin abrasions, or perinatal transmission.5 It is believed that the means of infection is through direct contact with the bodily fluids of humans or animals with the virus.5 The virus causes many of the same symptoms as the flu, such as muscle pains, fever, and general fatigue.5 It can also cause particularly bad hemorrhaging, or internal bleeding, which drastically decreases a victim’s chances of survival.5

Ebola virus is a part of the Filoveridae family.8 This is the taxonomic categorization of a number of related viruses with filamentous structure, an infectious capacity, and a genome in the form of single stranded RNA.8 Electron microscopy imaging has shown the Ebola virus to exist in a “U” or “6” shape.8 Structurally, the virus consists of a glycoprotein coated viral envelope housing a viral matrix.9 This matrix insulates a layer of nucleocapsid proteins in which the genome resides.9

The epidemic prompted a quick response on the public health front but it also sparked a massive surge in Ebola virus research on a molecular level. In order to have a more robust defense against the virus, there would need to be an effective means of intervention via vaccines or other therapeutics. Depending solely on a social and organizational response to the outbreak would have been dangerous seeing how deadly and contagious the disease was. Experiments suggest that the virus has many cell invasion schemes (depending on the cell type) – one of the reasons why it has become so deadly.10 Two of these proposed invasion mechanisms are receptor-mediated endocytosis and cell entry via lipid raft microdomains on the plasma membranes of healthy cells.10  Understanding the mechanisms behind viral attachment to the plasma membrane as well as viral release from a cell is crucial for effective development of therapeutics. This is because without fusion or release of viral particles from host cells they have virtually no way of further propagation.

Researchers have taken significant interest in looking at these lipid rafts as a means to create a vaccine or a lipid raft antigen delivering system. Lipid rafts are characterized as a combination of different glycoproteins, protein receptors, and specialized lipids that serve as hubs for signal reception, protein trafficking, and general bilayer structure.10 One of the main proteins that the Ebola virus genome encodes for is a functional glycoprotein (GP).8 The Ebola glycoproteins are amply spread around the viral envelope and are absolutely essential for the virus’s ability to interact with cell membranes.8 One experiment in particular showed that Ebola glycoproteins localized to lipid rafts of infected human monocytes.8 The infected monocytes were lysed and analyzed via an immunoblotting experiment  with the primary antibody anti-EBOVGP mAb showing GP/lipid raft interaction.8 In addition, tests were run to see whether the virus also exited the cell using these lipid rafts. Ganglioside M1 (GM1) is prevalent in lipid rafts and often involved in cellular trafficking. Cells were infected with non-GM1 containing viral particles and after incubation there were viral particles in the supernatant containing GM1 in their envelopes. This suggests incorporation of the distinguishing lipid as newly made viral particles exit the cell and take part of the host cell’s lipid membrane. With this information in hand, we can conclude that there is a potential avenue of drug development in targeting these GP and lipid raft fusion sites.

       Some researchers have also chosen to explore the possibility of using Ebola virus-like particles as a means of treatment.8 These particles have a similar viral structure to the Ebola virus but lack the full deadly genome of the virus. Not only do they have a similar structure, but they display a very similar array of GP’s and other viral envelope proteins. In addition, these Ebola virus-like particles can recognize the lipid raft binding domains and because of this, they could potentially serve as an effective means of recruiting or delivering antigens to the sites of Ebola virus/cell fusion.8 With a dense localization of specific antigens at the Ebola virus/cell binding domains, it is possible that one could induce a significant lack of fusion or a large recruitment of immune cells to the site. The possibility of mobilizing an immune system response directly to the sites of Ebola virus/cell fusion has been especially exciting for researchers and it is an idea still being explored. Not only are these virus-like particles a potential means of treatment but they can serve as a useful model of the Ebola virus without the deadly capacity. This discovery has allowed for safer and more accessible research. Just recently (March, 2016), there was an article published demonstrating the dependence of a fusion loop on the Ebola virus glycoprotein for successful fusion into host cells.11 They used virus-like particles for their experiments and the findings have provided another probable avenue of therapy by directing a focus on a specific region of the glycoprotein itself – the fusion loop.11

The Ebola epidemic of 2014 left a momentous mark on modern day global health.  It served to show us the health disparities around the world as well as the need to react quickly and efficiently to a disease of such lethal magnitude. From the macro social level down to the molecular level, it is of extreme importance that an effective epidemic response takes all factors into account. Research on potential therapies has given us a much better picture of how the virus functions and in what ways treatments will be most effective. The lipid raft domains of host cells and viral glycoprotein attachment sites have proved to play crucial roles in the proliferation of the virus. The urgency for action on the public health level has subsided, but we are still left with a continuous stream of research that will inevitably supplement our ability to combat future viral epidemics.  Ultimately, these findings further us along a road of bettering our response to diseases, such as Ebola, in order to treat the afflicted and save lives.


REFERENCES

  1. Bausch DG, Schwarz L (2014) Outbreak of Ebola Virus Disease in Guinea: Where Ecology Meets Economy. (2014, July 31). Retrieved October 08, 2016, from http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003056
  1. 2014 Ebola Outbreak in West Africa – Outbreak Distribution Map. (2016, March 17). Retrieved October 08, 2016, from http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/distribution-map.html
  1. Outbreaks Chronology: Ebola Virus Disease. (2015, July 18). Retrieved October 08, 2016, from http://www.cdc.gov/vhf/ebola/outbreaks/history/chronology.html
  1. Peters, C. J., & Peters, J. W. (1999). Outbreaks Chronology: Ebola Virus Disease. Retrieved October 08, 2016, from http://www.cdc.gov/vhf/ebola/outbreaks/history/chronology.html
  1. Martínez, M. J., Salim, A. M., Hurtado, J. C., & Kilgore, P. E. (2015, September 12). Ebola Virus Infection: Overview and Update on Prevention and Treatment. Retrieved October 09, 2016, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4675769/
  1. Berry, E. L. (2014, December 23). Ebola Virus 2014: Timeline of the World’s Largest Outbreak. Retrieved October 09, 2016, from http://www.medscape.com/viewarticle/836512
  1. Dahl, B. A., Kinzer, M. H., Raghunathan, P. L., Christie, A., DeCock, K. M., Mahoney, F., Bennett, S., Hersey, S.,  Morgan, O. (2016, July 8). CDC’s Response to the 2014–2016 Ebola Epidemic — Guinea, Liberia, and Sierra Leone. Retrieved October 09, 2016, from http://www.cdc.gov/mmwr/volumes/65/su/su6503a3.htm

 

  1. Bavari, S., Bosio, C. M., Wiegand, E., Ruthel, G., Will, A. B., Geisbert, T. W., … Aman, J. M. (2002). Lipid raft Microdomains. JEM, 195(5), . Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193767/
  1. Huang, Y. (2002, September ). The Assembly of Ebola Virus Nucleocapsid Requires Virion-Associated Proteins 35 and 24 and Posttranslational Modification of Nucleoprotein. Retrieved October 23, 2016, from Molecular Cell, http://www.cell.com/molecular-cell/fulltext/S1097-2765(02)00588-9
  1. Aleksandrowicz, P., Marzi, A., Biedenkopf, N., Beimforde, N., Becker, S., Hoenen, T., … Schnittler, H.-J. (2011). Ebola virus enters host cells by Macropinocytosis and Clathrin-Mediated Endocytosis.Journal of Infectious Diseases, 204(suppl 3), 957–967. doi:10.1093/infdis/jir326
  1. Lee, Jinwoo, Sonia M. Gregory, Elizabeth Nelson, Judith M. White, and Lukas Tamm. “The Roles of Histidines and Charged Residues as Potential Triggers of a Conformational Change in the Fusion Loop of Ebola Virus Glycoprotein.” PLOS ONE:. Plos, 29 Mar. 2016. Web. 07 Nov. 2016.

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