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Biology 103
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The Ebola Virus: Candidate for Genetic Mutation?

Jennifer L. Wilson

The Ebola virus has been a controversial topic since its discovery in 1976, having achieved considerable fame in the 1990's through the media and such works of fiction as the novel The Hot Zone and the film Outbreak. However little information regarding the virus' virulence and transmission methods is known by the general public, thus making it one of the most globally feared viruses. It has been speculated that one of the virus' strains--Ebola Reston--has "airborne" qualities, therefore making it transmittable via, well, air. While many scientists challenge this view and maintain that none of Ebola's four identified strains can be transmitted in such means, it provokes the question: how does a virus that kills its host so quickly ensure its progression and evolution?

The Facts: Origins, Transmission, and Symptoms

The Ebola virus, named after the river in Zaire where it was initially discovered, is a virulent filovirus that is known to affect humans and primates (though some argue that also affects plant life as well). Existing strains, as of 1998, include: "Ebola Zaire--discovered in Zaire in 1976, the first known occurrence of the Ebola virus; Ebola Sudan--initially discovered in the western Sudan in 1976, this type of Ebola virus resurfaced again in 1979 in Sudan; Ebola Reston--the variation of the Ebola virus discovered in African monkeys imported to the United not believed to cause health problems in humans; and Ebola Tai--the most recently discovered type discovered in 1995 on the Ivory Coast of West Africa in the Tai Forest." (1) All of these strains have similar structures (string-like in shape), but possess different gene sequences, and thus distinctive properties.

The virus is most commonly spread via personal contact. "Often, infection (in previous outbreaks) have occurred among hospital care workers or family members who were caring for an ill or dead person infected with Ebola. Blood and bodily fluids [have high concentrations of the virus], thus transmission has occurred as a result of hypodermic needles being reused in the treatment of patients. Reusing needles is not an uncommon practice in developing countries, such as Zaire, Gabon, and Sudan, where the healthcare system is significantly underfinanced." (2) Close contact with infected persons who are not symptomatic is not likely to result in transmission of the virus, though some scientists have argued that studies show that the virus may be present on the skin as a result of bodily excretions (i.e. perspiration). Furthermore, the virus is known to reproduce rapidly in the event that even small quantities are exposed to easily infectable areas of the body (i.e. eyes, mouth, and nasal cavity). "Patients who have completely recovered from an illness caused by Ebola virus do not pose a serious risk for spreading the infection. However, the virus may be present in the genital secretions of such persons for a period (up to seven weeks) after their recovery, and therefore it is possible they can spread the virus through sexual contact." (3)

The period of contagion lasts until the victim is completely recovered, and there are no remnants of the virus in the blood. However, if the victim expires, his/her corpse is extremely infectious, and therefore must be cremated to avoid further transmission. The virus is known to exist the longest in the victim's reproductive organs, hence making semen infectious for up to seven weeks following recovery.

The virus specifically affects liver cells and reticuloendothelial cells. Affected blood capillaries leak fluids and plasma proteins, causing intravascular coagulation and a zero clotting factor. The water volume loss in the body produces clinical shock, thereby causing the organs of the body to fail. The incubation period is typically from two to twenty-one days, and, depending on the victim, symptoms occur fairly shortly after transmission. "All forms of viral hemorrhagic fever begin with fever and muscle aches. Depending on the particular virus, disease can progress until the patient becomes very ill with respiratory problems, severe bleeding, kidney problems, and shock. With Ebola, persons develop fever, chills, headaches, muscle aches, and loss of appetite. As the disease progresses, vomiting, bloody diarrhea, abdominal pain, sore throat, and chest pain can occur. The blood fails to clot and patients bleed from injection sites as well as into the gastrointestinal tract, skin, and internal organs." (4) This last phase of the infection is known as the "bleed-out" phase, as the victim will typically bleed from every orifice. The following is a chart that lists the symptoms as they apply to a particular stage of the infection.

Time Frame Symptoms that occur in most Ebola patients Symptoms that occur in some Ebola patients Within a few days of becoming infected with the virus: high fever, headache, muscle aches, stomach pain, fatigue, diarrhea sore throat, hiccups, rash, red and itchy eyes, vomiting blood, bloody diarrhea Within one week of becoming infected with the virus: chest pain, shock, and death blindness, bleeding (5)

Fatality is approximately ninety percent with Ebola Zaire, and sixty percent with Ebola Sudan. No fatality rate has yet been determined for Ebola Tai, as only one known human has been infected--a Swiss scientist who contracted it from a chimpanzee but recovered successfully. As aforementioned, Ebola Reston is believed to be only hazardous to primates, and therefore has no human fatality rate as of yet either.

There is currently no cure or vaccine for any of the Ebola strains. "One of the keys to try to find a cure or vaccine for Ebola is to discover its' natural host. Although extensive research has been done, scientists have no evidence of the natural host of Ebola. Many people are under the misconception that monkeys are the natural host for Ebola. This is highly unlikely since monkeys die of Ebola as quickly as humans." (6) Presently, scientists can only recommend that patients undergo plasma albumin replacement prior to clinical shock, as antisera have yet to be developed. "Although it is believed that death results directly from the damage to internal tissues, it is not known why some patients manage to survive the disease...Convalescence is slow, often taking five weeks or more, and is marked by weight loss and amnesia in the early stages of recovery." (7) Questions regarding immunity from the virus have yet to be answered, as there is no definitive proof of the fact that recovered victims have come into contact with the virus for a "second clinical infection". However, it is assumed that immunity, if it exists, is strain-specific. Nonetheless, scientists are almost certain that reoccurrence is not a factor, as the virus has not yet demonstrated a latency period in its victims.

Biological Basis: Cell Properties

"Ebola Zaire has been completely sequenced and Ebola Reston is nearly completed. The gene order of these viruses reaffirms their independence as a family." (8)Such individualism has made it difficult for scientists to treat Ebola as they would other filoviruses, such as Marburg; however a great deal is known about the genetic structure and viral properties.

The virus is composed of ribonucleic acid (RNA). Such a structure unfortunately makes it prone to undergoing rapid genetic changes via one of three mechanisms: "1) nucleotide substitutions resulting from purportedly high error rates during RNA synthesis; 2) reassortment of the RNA segments of multipartite genomic viruses; or 3) RNA-RNA recombination between non-segmented RNAs...The Ebola virus can use only the first and the third mechanisms as it has only one segment of RNA by capsid"(9) (the protective coating of proteins). Thus, scientists have asserted that, with regards to concerns about the virus being airborne, the genome (RNA) would have to mutate to the point where the protein capsids are immune to adverse air qualities (i.e. dryness). Furthermore, the genome would have to mutate in a way that allows the virus to be transmittable via respiratory function. Scientists insist that the chances of the virus mutating to this degree are small, despite speculations about the airborne transmission of Ebola Reston.

Replication of the virus takes approximately eight hours, and can occur several times before the onset of symptoms. "Hundreds to thousands of new virus particles are then released during periods of hours to a few days, before the cell dies." (10) Such a property induces arguments with regards to the virus' lack of a latency period, and gives rise to my query:

How Does the Virus Ensure Its Evolution?

"Previous outbreaks of Ebola appear to have continued only as long as a steady supply of victims came in contact with body fluids from the infected...Ebola's virulence serve[s] to limit its spread: it's victims die so quickly that they don't have a chance to spread infection very far." (11) Hence, it can be asserted that Ebola has failed to secure any long-term vectors, as primates, who die of the disease just as quickly as humans, are merely short-term vectors. So why does Ebola kill its host so soon after initial infection?

First of all, one must consider the means of transmission. Any virus that is transmittable via bodily fluids is clearly a candidate for progression in the absence of awareness education and proper medical facilities (i.e. HIV). However one must focus on the final phase of the infection, which results in a complete liquefaction of the organs, or "bleed-out". The transmission rate in such a situation immediately goes from medium to high provided that other potential victims are nearby. Thus, one may assume that this final phase of infection is the primary means for the virus to ensure its progression, regardless of the fact that it destroys its host, in most cases.

Secondly, one must consider epidemiological factors. For a major epidemic of the virus, conditions include: " Presence of the animal or insect vectors, whatever they may be, in proximity to a human population; 1) exposure of even a single infected human to others, by traveling from a remote setting, to a population center after exposure to a vector and/or reservoir in that remote setting; 2) deficient sanitation and hygiene among the population (lack of clean water supplies, sewage disposal & treatment, etc.) which increases the chance of bodily fluid contact (e.g., contact with fresh sewage containing wastes from Ebola victims); 3) decreased immune response in members of the population, whether from malnutrition or other disease burdens, especially AIDS; 4) social customs which increase bodily fluid contact between people (e.g., burial customs, multiple-partner sex); 5) inadequate public health infrastructure (hospitals, staff, equipment - e.g., enough syringes to prevent their re-use, isolation facilities, barrier supplies); 6) lack of awareness of the disease and its symptoms among the population; 7) access to transportation systems; 8) poor communications infrastructure, resulting in delays in medical response and public notification & education; 9) the mutation of Ebola so that a strain that is dangerous to humans becomes airborne." (12) While the last condition is currently not an issue, it is also the most grave of the conditions, and would allow an epidemic of the Ebola virus to reoccur in vast proportions. Furthermore, it may be assumed that airborne transmission is the best possible trait for the virus, as a mutation of this degree would ensure its continued evolution and progression.

And lastly, one must consider the behavioral science, if you will, involved in a virus' interactions with its victim. "If any virus has only one possible host species, then it might enjoy only limited success by a strategy of killing its hosts in short order (thereby losing opportunities for transmission to new hosts). Each infectious agent must achieve its own peculiar balance between aggressively replicating and spreading through a host's tissues, and permitting infected hosts to survive long enough for transmission. Many different combinations of infectivity and pathogenicity can make an infectious agent successful. Keep in mind Ebola, like many viruses, is not limited to a single host species... [One may] guess that the dramatic pathology of Ebola infections in humans is due to its poor adaptation to using humans as hosts. If humans are incidental to the natural history of Ebola (that is, if Ebola has evolved in a stable relationship with some other host), then this virus' limited success in human populations is not a problem for the virus. While infections are devastating for infected people, the virus should not suffer because of its poor adaptation (e.g. limited transmissibility) to the human host. In its natural host, presumably, Ebola life goes on happily. A virus can't do something just because it would be beneficial, it can only do what it has evolved the capability to do (in a specific host)." (13) Hence, the virulence of Ebola with respect to the human and primate populations is presumably a result of its ability to successfully evolve unaffected in its original host, assuming one exists.

Concluding Remarks

A virus seeks out a host that is capable of transmitting it to as many additional hosts as possible. If any host in the chain of transmission expires within a short period of time, then the progression of the virus is arrested. Hence, the infectious qualities of the virus in question are limited by the virus' degree of virulence--its ability to claim multiple victims and produce fatal symptoms. Thus, considering that the former characteristic of virulence is the most limiting factor for the Ebola virus, is its evolution guaranteed? Is the Ebola virus a candidate for genetic mutation, and what is the rationale behind a pathogen that lacks a prolonged latency period?

The answers to the above questions are not yet determinable with regards to the Ebola virus, for it is still a relatively new virus. While the genome has been sequenced, a number of questions still remain unanswered. While scientists have yet to discover all of the mysteries behind viral behavior, it may be assumed that Ebola has ensured its progression and subsequent evolution through its ability to be transmitted via short-term vectors.

WWW sources

1)Healthlink USA , links to medical web sites

2)Healthlink USA , links to medical web sites

3)Healthlink USA , links to medical web sites

4)Healthlink USA , links to medical web sites

5)Center for Disease Control, Center for Disease Conrtrol web site

6)Healthlink USA , links to medical web sites

7)Healthlink USA , links to medical web sites

8)Healthlink USA , links to medical web sites

9)Healthlink USA , links to medical web sites

10)Healthlink USA , links to medical web sites

11)Healthlink USA , links to medical web sites

12)Healthlink USA , links to medical web sites

13)University of Cape Town, University's microbiology web page

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