Ebolavirus

Ebolavirus: will you survive the week? By: Meaghan O'Day Thursday Lab Period




 * Introduction **

 Ebolavirus, also known as EBOV, is a negative strand RNA virus that is found in the filoviridae family. It is one virus capable of causing Viral Hemorrhagic Fever (VHF), which displays symptoms of high fever and massive bleeding, and the virus kills 90% of the people it infects (MedicineNet). I was interested in studying the Ebolavirus because it is something that had caught my interest when mentioned in anatomy; I thought that further research would be appropriate in expanding my knowledge about the virus and to learn what disease was actually caused. After learning about the topic in anatomy I had also heard about an instance that sounded similar to Ebola, however I had never heard if this was actually the cause of the situation. From what I understand about the incidence, an individual left any area where they could have contact with those who were important to them and died within a week after experiencing extreme internal and external bleeding. Although I never heard the full medical side of the story, I was pretty sure the individual was infected with Ebola.


 * Symptoms **

 Symptoms of VHF resulting from an infection of Ebolavirus include early, mild symptoms and later, more extreme ones. The earlier symptoms occur within the first few days of infection and include sore throat, headache, muscle pain, severe weakness, fever, and diarrhea. The earlier symptoms could possibly be mistaken for a less severe situation such as a common cold, a common fever, or the flu. However, Ebola is definitely noticeable when the later symptoms take effect within a week of infection. The later, more severe symptoms include vomiting blood and profuse internal and external (nose, eyes, gum) bleeding. (Glausiusz, 24). A few other random symptoms have also been recorded such as dysphagia and hiccups (CDC, 373). Death is usually the final result from blood loss, shock, or dehydration.




 * Infection of Ebola **

 One is infected by Ebola after experiencing contact with bodily fluids of someone who has already been infected or from handling an animal carcass after death from Ebola. Via entering bodily fluids, Ebola enters the blood stream and floods it with a glycoprotein while a protein version of the glycoprotein remains attached to the virus. The glycoprotein in the blood then fastens onto a neutrophil white blood cell so that it can no longer combat invader cells or signal other fighter cells. (Glausiusz, 24). The glycoprotein is able to fasten to the white blood cell because Ebolavirus is in the shape of a spike protein. This structure is necessary for viral entry into human cells providing for the perfect ability for attachment and fusion with the host cells, followed by entry (Lee, 1).

 This picture represents the crystal structure of Ebolavirus glycoprotein. It has a three-lobed chalice-like structure. The structure allows for attachment to the host cells (GP1), fusion of the viral membrane with host cells (GP2), which is followed by entry and infection of the host cells. Scientists can use this structure to create vaccines and antibodies that would be effective in attacking Ebolavirus. “The structure identifies the probable cleavage site and illustrates how cleavage at this site uncaps the receptor-binding regions, freeing them for interaction with host-cell receptors,…reveals that most of GP is shielded by a thick cloak of carbohydrate and identifies the very few sites left exposed and available for antibody binding” (Lee, 2).

 After the glycoprotein attaches to the host cells, Ebolavirus can subvert the cell’s genetic machinery and close itself while damaging the endothelial cells, weakening the blood cells which become leaky, leading to extreme internal and external bleeding (Glausiusz, 24).




 * Death **

 Death from VHF results from blood loss, shock, or dehydration. The most common cause of death is victims bleeding to death, however shock may occur because of falling blood pressure levels as the circulatory system would be unable to pump blood to all vital organs. With the speed of symptoms after infection the immune system does not have enough time to call on an antibody response to the viral infection.




 * Vaccine **

 I found two studies that have taken place in an attempt to find a vaccine for Ebolavirus. The first study attempted to create a vaccine consisting of the gene that codes for the glycoprotein spliced into a plasmid. The vaccine was experimentally injected into guinea pigs. Results found that guinea pigs injected with the vaccine were able to develop an immune response in time to counter the Ebolavirus they had been infected with. This vaccine has yet to be tested on humans; the most desired spot for human testing is in sub-Saharan Africa, where Ebolavirus has been most prevalent (Glausiusz).

 The second study I found used “L-FCN/MBL variants that contained the MBL carbohydrate recognition domain and varying lengths of the L-FCN collagenous domain” (Michelow, 24729) in an attempt to develop molecule therapies aimed at viral elimination. MBL (Mannose-binding lectin) and L-FCN (L-ficolin) because of their functions as antibodies and ability to activate complements. MBL was particularly important in this experiment in that it “recognizes the conserved sugars that decorate the cell walls of many Gram-positive and Gram-negative bacteria as well as the surface glycoproteins of viruses like influenza virus, HIV, severe acute respiratory syndrome coronavirus, and Ebola virus” (Michelow, 24730). The goal of the experiment was to generate novel recombinant chimeric fusion proteins using human MBL, L-FCN, and other enhanced effector functions. The study found that L-FCN/MBL76 demonstrated a strong inhibition of wild type-like Ebola Zaire virus in the cell based infection model (Michelow, 24734).

<span style="font-family: 'Trebuchet MS',Helvetica,sans-serif;"> Finding a vaccine is important because Ebolavirus is a Centers for Disease Control and Prevention Category A agent, representing a substantial threat to public health as it causes rapid and fatal viral hemorrhagic fever.


 * <span style="font-family: 'Trebuchet MS',Helvetica,sans-serif;">History of Outbreaks of Ebolavirus **

<span style="font-family: 'Trebuchet MS',Helvetica,sans-serif;"> The first recorded Ebola outbreak occurred between the years 1976-1979 in the African regions of Sudan and Zaire. The outbreak in Sudan was caused by Ebola Sudan, with a mortality rate of 53%. The outbreak in Zaire occurred shortly after and was due to E. Zaire, with a mortality rate of 89%. The last outbreak during this time period occurred in Nzara, Sudan in 1979 (caused by E. Sudan from the previous outbreak) with a mortality rate of 65% (Pourrut, 1006). E. Sudan and E. Zaire were the first emerged Ebolaviruses recorded.



<span style="font-family: 'Trebuchet MS',Helvetica,sans-serif;"> The second period of Ebola outbreak occurred between 1994-1997. E. Ivory Coast, a new subtype, was identified during this resurgence. The first case within this period was the diagnosis of a female Swiss ethnologist who had autopsied a dead chimpanzee in the Tai National Park in Ivory Coast. This infection was followed by the most noticeable Ebola outbreak, which occurred in the town of Kikwit. Within a seven month period Ebola killed 256 of 315 victims, with a mortality rate of 81%. The outbreak in Kikwit was followed by three more: one in northeastern Gabon (mortality rate of 59%), the second in the villages of Mayibout I and II (mortality rate of 67.7%), and the third in Booué (mortality rate of 75%). The outbreak in Booué was significant because of its wide geographic range, traveling through Booué, Gabon, Libreville, Lastourville, and Johannesburg (Pourrut, 1007).

<span style="font-family: 'Trebuchet MS',Helvetica,sans-serif;"> The third recorded period of Ebola outbreak was between 2000-2004. A significant feature of this period was the infection of Ebolavirus in large animal species such as gorillas and chimpanzees (Pourrut, 1007). Outbreaks were recorded in Mekambo, Mendemba, Ntolo, Ilahounene, Ekata, Olloba, Makokou, Entsiami, Abolo, Ambomi, Kelle, Mbomo, Yembelengoye, and Mvoula (Pourrut, 1007-1008).


 * <span style="font-family: 'Trebuchet MS',Helvetica,sans-serif;">Conclusion **

<span style="font-family: 'Trebuchet MS',Helvetica,sans-serif;"> Action must be taken to counter the Ebolavirus. It represents a considerable threat to public health and could possibly be used in acts of terrorism. However, recurrence of Viral Hemorrhagic Fever related to Ebolavirus in affected regions of Africa has decreased because of the institution of protective interventions including “training of medical and relief personnel on the proper use of protective equipment, initiation of aggressive case-finding, and educational measures in the community” (CDC, 373). These are important steps to take in preventative measures against Ebolavirus.

<span style="font-family: 'Trebuchet MS',Helvetica,sans-serif;"> I found learning about the Ebolavirus fascinating. Its features are extremely complex, its abilities astounding, although deadly. I find it impossible to believe that a single virus could kill a human being of any strength within a week. Even though our immune system has the ability to fight off infections such as the common cold and the flu, the Ebolavirus is strong enough and fast enough to mask itself in our immune system and take down a human life.

<span style="color: #0000ff; font-family: 'Trebuchet MS',Helvetica,sans-serif;">Literature Cited

<span style="color: #0000ff; font-family: 'Trebuchet MS',Helvetica,sans-serif;">Glausiusz, Josie. Ebola’s Lethal Secrets. Discover, 24 (1998).

<span style="color: #0000ff; font-family: 'Trebuchet MS',Helvetica,sans-serif;">CDC. Update: Outbreak of Ebola Viral Hemorrhagic Fever – Zaire, 1995. Published online in JAMA 274, 373-374 (1995).

<span style="color: #0000ff; font-family: 'Trebuchet MS',Helvetica,sans-serif;">Lee, J.E., et al. Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor. Published online in Nature 454, 177 (2008).

<span style="color: #0000ff; font-family: 'Trebuchet MS',Helvetica,sans-serif;">Michelow, Ian C., et al. A Novel L-ficolin/Mannose-binding Lectin Chimeric Molecule with Enhanced Activity against Ebola Virus. Published online in The Journal of Biological Chemistry 285, 24729-24739 (2010).

<span style="color: #0000ff; font-family: 'Trebuchet MS',Helvetica,sans-serif;">Pourrut, Xavier, et al. The natural history of Ebola virus in Africa. Published online in Science Direct Microbes and Infection 7, 1005-1014 (2005).