Ebola Virus
The Agent 
Courtesy: CDC
Dr. Lyle Conrad
Ebola viruses cause a severe illness known as Ebola hemorrhagic fever that can be lethal to humans and nonhuman primates. Although hemorrhagic fever can be brought on by several types of viruses, Ebola produces one of the most deadly forms of viral hemorrhagic fevers. Many of the symptoms of hemorrhagic fever – fever, headache, aches, weakness, vomiting, and diarrhea – are common in other types of viral infections, but with severe cases of hemorrhagic fever there can be damage to blood vessels and extensive internal and external bleeding (hemorrhage). Mortality rates for Ebola hemorrhagic fever are high, ranging from 50% to 90%, with death usually occurring from shock rather than blood loss. The virus is transmitted through direct contact with blood or other body fluids of infected persons or animals, and even close contact with a deceased Ebola-infected body.
Ebola viruses belong to a family of viruses termed Filoviridae, which are characterized by a long filamentous structure. There are four subtypes of Ebola viruses: Zaire, Sudan, Côte d’Ivoire, and Reston, each named after the location in which they were first identified. The first three subtypes are found in Central Africa and cause severe hemorrhagic fever. The Reston subtype is found in the Western Pacific and although it is highly pathogenic in nonhuman primates, it is not known to cause illness in humans.
Courtesy: CDC/
Frederick A. Murphy
Ebola was first recognized in 1976 as the cause of outbreaks of disease in the Democratic Republic of the Congo (then known as Zaire) and in Sudan. Some 300 people in each country became infected. The mortality rate was 88% in Zaire and 53% in Sudan (the Zaire subtype is the most deadly). Although the circumstances of the original human infections are not known, the disease spread through close direct contact and as a result of unsafe and unsanitary hospital practices, such as the use of contaminated needles and the lack of sufficient containment measures. Smaller outbreaks occurred again in 1977 and 1979 in the same regions. Sporadic outbreaks of the Zaire and Sudan Ebola subtypes have erupted over the succeeding years in the Democratic Republic of the Congo, Gabon, Uganda, and Sudan. Ebola virus most recently resurfaced in September of 2007 in the Democratic Republic of the Congo. In total, there have been over 1800 cases of human Ebola infections and nearly 1300 deaths.
The Reston subtype of Ebola virus was first identified in 1989 in the United States in monkeys housed in a quarantine facility in Reston, Virginia. At least four humans became infected, but none became ill. Additional outbreaks of the Reston subtype occurred between 1989 and 1996 in Texas, Pennsylvania, and Italy. No humans suffered illness in any of these cases. The source of all the Reston subtype outbreaks was traced to a single facility in the Philippines that exported the monkeys.
In late 2007, a fifth strain of Ebola virus emerged in western Uganda. The new species of the virus appears to be relatively mild, but officials at the World Health Organization are concerned about it because symptoms include vomiting, which is different from the other strains.
Where does the Ebola virus go in between outbreaks? As for other viruses, the survival of Ebola depends upon a host organism(s). Humans are not the host organism - or natural reservoir - of Ebola viruses. Humans become infected when they come into contact with an infected host, although once humans become infected they can transmit Ebola to other people. The identification of the natural reservoir of a virus is of great interest to scientists, because this knowledge gives information as to the geographic range and ecological areas where humans may come in contact with animals or insects that may be the source of the disease; this may allow scientists to more readily contain outbreaks.
In 2005 it was reported that fruit bats may serve as the natural reservoir of Ebola. Researchers trapped small animals found near Ebola-infected gorilla and chimpanzee carcasses over a period of time between 2001 and 2003. They found evidence that three species of captured fruit bats showed evidence of symptomless infection – that is the bats had Ebola-specific genetic sequences in their bodies or evidence of an immune response to Ebola even though they did not exhibit signs of the disease. Fruit bats live in regions of Africa that include areas where Ebola outbreaks have occurred and are eaten by people in central Africa. These animals may play a key role in transmitting Ebola to great apes and humans. Bats have been implicated as a reservoir of other viruses that cause deadly diseases including SARS and Marburg, a virus related to Ebola that also causes hemorrhagic fever.
The Problem
Ebola virus is a class A bioterrorism agent, known to cause highly lethal hemorrhagic fever. The mortality rate can be as high as 90%. Because the Ebola virus is so hazardous, it is classified as a biosafety level 4 agent - the level assigned to the most dangerous agents known. Research using Ebola viruses requires facilities with the utmost levels of containment, strict controls on access, and highly trained personnel.
There is no cure for Ebola hemorrhagic fever, no established drug therapy to treat Ebola infection, and no vaccine that can protect humans against Ebola. Scientists lack sufficient diagnostic tools to rapidly identify Ebola infections. Scientists also need a more thorough understanding about how the virus is transmitted and how it causes disease.
In addition to being classified as a potential bioterrorism agent, the risk of continued natural outbreaks or the further emergence of Ebola remains a concern. As the human population grows and increased human contact with bats or Ebola-infected non-human primates occurs, it is likely that additional natural outbreaks of Ebola will occur.
Ebola is a threat not only to humans but also to our closest living relatives - the great apes. The western lowland gorilla populations have been decimated by Ebola to such an extent that they are now considered "critically endangered". About a third of the gorillas in protected areas have died from Ebola in the past 15 years. Scientists are concerned that their numbers may not be able to recover and fear that they could become extinct in as soon as a decade. Gorillas are threatened further by poaching, civil unrest, and habitat destruction.
The Research
One of the key steps in any virus infection occurs very early in an infection cycle. That is the step where a virus binds to and enters a cell in a susceptible host organism. Because viruses are too small to reproduce on their own, they must invade a host cell in order to multiply and produce more copies of themselves that can then go on to infect other organisms and continue the infection cycle.
Many viruses require a specific protein or other type of molecule on the surface of the host cell - called a receptor - which allows the virus to pass into a cell of a host organism. If an organism or cell type does not possess this particular receptor, the virus is unable to infect that organism or cell type. Knowing what this receptor is for any particular virus is a crucial piece of information for scientists, because it tells them which organisms or cell types are susceptible to infection by a certain virus. Furthermore, this knowledge can be used to design therapies that may be able to prevent a virus from entering into a cell and initiating an infection.
Precisely how the Ebola virus enters cells is unknown at present. It is known that in humans, the Ebola virus appears to infect many different cell types. Ebola is also thought to have a broad host range, since it is capable of infecting diverse mammalian species, including primates, rodents, and bats.
Dr. Richard Sutton and members of his laboratory in the Department of Molecular Virology and Microbiology (MVM) at Baylor College of Medicine (BCM) are working to identify the elusive Ebola virus receptor. Based on evidence from other scientists that suggested that members of a group of proteins named the Tyro3 family might mediate entry of Ebola virus into cells, Dr. Sutton’s group tested what would happen if they reduced the levels of the Tyro3 proteins in cells. They reasoned that if these proteins were necessary for entry into cells, reduction of their levels should diminish infection by Ebola. However, they observed little effect on Ebola virus infection when they reduced levels of expression of all three Tyro3 family genes. They therefore concluded that it is unlikely that this family of proteins is the sought-after entry factor for Ebola virus.
They are currently pursuing a different tactic, known as a negative genetic screen, to identify the cellular receptor that Ebola utilizes to gain entry into cells. The basic rationale behind this approach is that if a cell is manipulated so that it no longer makes the Ebola receptor, then this cell will become resistant to infection by Ebola virus. Then the protein that is no longer made in Ebola resistant cells is identified and analyzed and after rigorous testing, the identity of the Ebola receptor may be discovered.
To date, Dr. Sutton and his group have infected susceptible cells with specially designed vectors that individually disrupt the expression of a large number of host cell genes. They then sought cells that were resistant to entry by an Ebola protein. After many repetitions of this technique, they obtained clones of cells that resist entry by the Ebola protein. The investigators are now in the process of analyzing these cell clones to determine which genes are not being expressed. These genes would be candidates for a receptor for Ebola virus. In the end, they hope to achieve a better understanding of Ebola virus cell binding and entry, with an eye towards therapeutic intervention.
For more information:
http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola.htm
http://www.who.int/csr/disease/ebola/en/
http://www.nlm.nih.gov/medlineplus/ency/article/001339.htmLearn more about: