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Molecular Virology and Microbiology

Houston, Texas

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Department of Molecular Virology and Microbiology
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Ebola Virus

The Agent

1976 photograph of two nurses standing in front of Ebola case #3, who was treated, and later died at Ngaliema Hospital, in Kinshasa, Zaire

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 percent to 90 percent, 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.

Electron microscope image of Ebola virus taken in 1976 showing its filamentous structure

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 percent in Zaire and 53 percent 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 July of 2009, the discovery of the Reston subtype in domestic pigs in the Philippines was reported. Genetic analysis suggests that the virus has been widely circulating in swine for many years, possibly even before the 1989 outbreak in the United States. The virus has been detected in farmers who have had contact with infected pigs, but they have not shown any signs of illness.

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 percent. 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.

String-like Ebola virus particles are shedding from an infected cell in this electron micrograph.

Credit: NIAID

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.

A new concern is the recent discovery of the Reston subtype of Ebola virus in pigs. This form of Ebola virus had previously been detected only in monkeys and humans, and it becomes a concern when a virus is found in a new host especially one that people have close contact with. Pigs are particularly worrisome because they are ideal hosts in which viruses can mix and mutate. Although the Reston subtype has not caused illness in humans to date, it is possible that the virus could become more dangerous after passage through pigs.

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, while in the Department of Molecular Virology and Microbiology at Baylor College of Medicine, worked 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 have since switched to a different tactic, known as a negative genetic screen, in an attempt to identify the cellular receptor that Ebola utilizes to gain entry into cells. Through this work, they hope to achieve a better understanding of Ebola virus cell binding and entry, with an eye towards therapeutic intervention.

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