A virus whose very reputation has solidified itself as a pathogen of fear, Ebola is one of the most notorious, pathogenic, and fatal. It is a filovirus, a family of viruses that “can cause severe hemorrhagic fever in people and nonhuman primates (such as monkeys and gorillas) and may spread in other animals, such as bats.” (Filoviruses (Filoviridae) | Viral Hemorrhagic Fevers (VHFs), 2021). First described in 1976 after an outbreak near the Ebola River, for which the virus is named in what is now the Democratic Republic of Congo, the most recent outbreak was only “declared over on June 19, 2021” (History of Ebola Virus Disease (EVD) Outbreaks, n.d.). Scientists, medical experts, and government officials work tirelessly to predict and plan for the next outbreak, but its zoonotic nature makes that task nearly impossible. One thing is for certain: there will be another. In the meantime, all that can be done is to prepare and learn.
The Ebola Virus, exists as “heterogenous, filamentous, enveloped virus particles containing a negative-sense, single-stranded RNA genome packaged within a helical nucleocapsid” (Bharat et al., 2012) While individual particles have a fairly consistent diameter of 80nm, they have a widely variable “length of 600-1,400nm” (Aleksandrowicz et al., 2011) The nonsegmented negative-strand RNA based genome of ebola contains just seven genes with a total length of about 19 kb. Each of these genes is either “separated by intergenic regions (IRs) of variable length” or they overlap. For clarification purposes, “the” Ebola virus is not just one virus. It’s a genus of viruses. While some are more common than others, other known species within the genus are the “Zaire ebolavirus), Sudan virus (species Sudan ebolavirus), Taï Forest virus (species Taï Forest ebolavirus, formerly Côte d’Ivoire ebolavirus), Bundibugyo virus (species Bundibugyo ebolavirus), Reston virus (species Reston ebolavirus), and Bombali virus (species Bombali ebolavirus)” (What Is Ebola Virus Disease? | Ebola (Ebola Virus Disease), n.d.)
But what does this mean? How exactly does Ebola spread from and infect person to person, and what is it so deadly? Most people think about cells as little bubbles. This isn’t far from the truth, but unlike bubbles, the outside of a cell actually allows for things to cross from the outside in, or inside out. After all, a cell’s got to “eat”. The Ebola virus takes advantage of this basic biological need by using its own glycoproteins to bind to the cells surface thereby triggering a response allowing itself to be “eaten” through a “non-specific engulfing process called macropinocytosis” (Ebola Virus: How It Infects People, and How Scientists Are Working to Cure It – Science in the News, 2014), which happens with a wave-like motion of the cell membrane. Once inside, a biological con with dire consequences begins.
Virtually all cells, especially our cells, have the ability to make more of themselves, or replicate. Viruses do not. Virtually all cells possess a functional ability to make their own proteins through an RNA based-process called transcription and translation. Most viruses function by hijacking that very system to instead make more of themselves. After entering the cell, the virus’ RNA, or ribonucleic acid, is uncoated thereby allowing itself to be read and rewritten over and over again, as the new viral particles travel to the host cells membrane to “bud off”, stealing portions of the host cells membrane to incase its own RNA before traveling off into the organismal abyss to infect more cells. A closer look at this process reveals an intriguing biological process. Remember that the RNA genome of ebola contains just 7 genes that either overlap or are separated by intergenic regions of variable length. The viral polymerase accesses the host cells genome at the “3′ promoter region and successively transcribes the viral genes following a stop-start mechanism at each gene boundary, which results in the production of discrete mRNAs from each gene”. (Brauburger et al., 2016) This and ebola’s own glycoproteins disrupt the host cell’s ability to bind and scaffold with neighboring cells which begins a downward domino effect later on.
After entering the body, Ebola initiates and repeats that process of replication at very specific cells such as the “liver cells, cells in the immune system, and endothelial cells, which line the inside of blood vessels.” (Ebola Virus: How It Infects People, and How Scientists Are Working to Cure It – Science in the News, 2014). One of the main symptoms that Ebola is known for is a hemorrhagic fever. By infecting the lining of blood vessels and disrupting adhesion, the scaffolded extra-cellular matric begins to break down like the walls of an old dam, leading to internal bleeding.
The liver is the body’s detoxifying center. Infection of that means that the body’s ability to detoxify is now compromised. Immune cells travel throughout the body, so by infecting immune cells, Ebola is able to rapidly spread throughout the body, leading to the quick onset of severe symptoms that is characteristic of the virus. The breakdown of these vital body systems, as well as the onset of water and electrolyte draining symptoms such as diarrhea and vomiting eventually lead to shock, organ failure, and death.
To further understand the nature of the virus, we have to understand where it comes from. Outbreaks all have the same origin in a sense. An outbreak cannot occur without the infection spreading from person to person, and it can’t spread person to person without a person first being infected. This moment, when Ebola first infects a person, is called a spillover event. Contact with an infected nonhuman primate or fruitbat, or the ingestion of bushmeat are common sources. But these sources are also reservoirs, places where the virus hides away in between outbreaks. This zoonotic nature of the virus is part of what makes it so difficult to control, predict, or eradicate. Once the first person is infected, and once symptoms have emerged, they themselves can spread the virus.
Spread occurs through direct contact. That means through broken skin or through the mucous membranes of the nose, eyes, or mouth. This may be through blood or other body fluids such as “urine, saliva, sweat, feces, vomit, breast milk, amniotic fluid, and semen of a person who is sick with or has died from Ebola virus disease (EVD)” (Transmission | Ebola Hemorrhagic Fever, n.d.), objects contaminated by infected bodily fluids, or even the semen of a man who has previously recovered from EVD. Symptoms begin appearing anywhere between 2 and 21 days after contact. Such a range is yet another challenging aspect of this virus. However, the average time between contact and onset of symptoms is 8 to 10 days. First come the so-called “dry” symptoms. Fever, fatigue, and generalized aches and pains. As time goes on, the so-called “wet” symptoms such as vomiting and diarrhea rear their head. The problem is, many of these early symptoms closely mirror those of other common infections “including influenza (flu), malaria, or typhoid fever.” (Signs and Symptoms | Ebola Hemorrhagic Fever, n.d.)
Once infected, there is little that can be done for treatment. According to the Center for Disease Control, there are two U.S. Food and Drug Administration (FDA) treatments that have been approved for use with both adults and children. The first is called Inmazeb and was approved in October of 2020. It is a combination of three monoclonal antibodies, a type of treatment that has gained public notoriety throughout the COVID-19 pandemic. The second was approved just 2 months later and is called Ebanga, this one a single monoclonal. Monoclonal antibodies lab produced or manufactured proteins “that act like natural antibodies to stop a germ such as a virus from replicating after it has infected a person.” (Treatment | Ebola (Ebola Virus Disease), n.d.). These proteins function by seeking out those aforementioned surface glycoproteins, thereby blocking the virus from its mode of cell entry. If these are not available or are no longer an option, the focus becomes providing supportive care.
Of course, prevention is always the best practice. Ebola has been the targeted focus of vaccine development for decades. There are now two regulatorily approved vaccines against the Ebola virus “rVSV-ZEBOV, a single-dose vaccine, made by Merck; and the two-dose Ad26.ZEBOV/MVA-BN-Filo, made by Janssen Vaccines and Prevention.” (Bausch, 2021, 580) Unfortunately, the locations where outbreaks tend to occur tend to also be volatile conflict and civil unrest epicenters which complicates effective and safe vaccine rollout campaigns. Additionally, the relative rarity of the disease, despite the immense impact of outbreaks that have occurred, poses another challenge: how do you effectively target vaccination efforts in a range of roughly 1 billion people for a disease that has only ever infected about 40,000? Of course, economic cost-benefit analyses come into play as well, but that’s far more a conversation of equity and justice than it is biology. Besides, the “economic burden of the West Africa outbreak is estimated to be over US$50 billion.” (Bausch, 2021, 581)
Violent symptomology aside, perhaps one of the largest reputation builders of ebola is its mortality rate. With an average case fatality rate of about 50%, historic “fatality rates have varied from 25% to 90%”. (Ebola Virus Disease, n.d.) The reasons why vary from biological to socioeconomic and/or geopolitical. Nevertheless, the ebola virus is a harbinger of doom. The CDC reports that during the 2014 Ebola outbreak, the affected area saw 28,652 cases and a minimum of 15,261 deaths. The countries of Guinea, Liberia, and Sierra Leone each had a minimum of 500 cases each. Effective contact tracing, education, isolation of the sick, and safe and sanitary burial of the dead are essential to controlling and minimizing an outbreak. Unfortunately, a lack of effective medical infrastructure, poor government response, and communication, customary burial and mourning practices, superstition, conspiracy, and a lack of education on what exactly ebola is and how to prevent it within the local inflicted populations are just a sample of the reasons Ebola outbreaks get as bad as they do.
References
Bausch, D. G. (2021, April 5). The need for a new strategy for Ebola vaccination. Nature Medicine, 27, 580-581. https://doi.org/10.1038/s41591-021-01313-w
Bharat, T. A. M., Noda, T., Riches, J. D., Kraehling, V., Kolesnikova, L., Becker, S., Kawaoka, Y., & Briggs, J. A. G. (2012, March). Structural dissection of Ebola virus and its assembly determinants using cryo-electron tomography. Proceedings of the National Academy of Sciences of the United States of America, 109(11), 4275-4280. https://doi.org/10.1073/pnas.1120453109
Brauburger, K., Boehmann, Y., Krahling, V., & Muhlburger, E. (2016, January 28). Transcriptional Regulation in Ebola Virus: Effects of Gene Border Structure and Regulatory Elements on Gene Expression and Polymerase Scanning Behavior. Journal of Virology, 90(4). https://doi.org/10.1128/JVI.02341-15
Ebola Virus Disease. (n.d.). WHO | Regional Office for Africa. Retrieved November 29, 2021, from https://www.afro.who.int/health-topics/ebola-virus-disease
Ebola Virus: How it infects people, and how scientists are working to cure it – Science in the News. (2014, October 14). Science in the News (Harvard University). Retrieved November 29, 2021, from https://sitn.hms.harvard.edu/flash/2014/ebola-virus-how-it-infects-people-and-how-scientists-are-working-to-cure-it/
Filoviruses (Filoviridae) | Viral Hemorrhagic Fevers (VHFs). (2021, September 2). CDC. Retrieved November 29, 2021, from https://www.cdc.gov/vhf/virus-families/filoviridae.html
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Signs and Symptoms | Ebola Hemorrhagic Fever. (n.d.). CDC. Retrieved November 29, 2021, from https://www.cdc.gov/vhf/ebola/symptoms/index.html
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Treatment | Ebola (Ebola Virus Disease). (n.d.). CDC. Retrieved November 29, 2021, from https://www.cdc.gov/vhf/ebola/treatment/index.html
Aleksandrowicz P, Marzi A, Biedenkopf N, Beimforde N, Becker S, Hoenen T, Feldmann H, Schnittler HJ. Ebola virus enters host cells by macropinocytosis and clathrin-mediated endocytosis. J Infect Dis. 2011 Nov;204 Suppl 3(Suppl 3):S957-67. doi: 10.1093/infdis/jir326. PMID: 21987776; PMCID: PMC3189988.
