The Ebola Virus

The Ebola Virus is the common name for several strains of virus, three of which are known to cause hemorrhagic fever in humans, which is characterized by massive bleeding and destruction of internal tissues. Named for the Ebola River in Zaire, Africa, where the virus was first identified, the Ebola virus belongs to the family Filoviridae. Three strains of Ebola virus that are often fatal to humans have been identified. Named for the areas in which the first recognized outbreaks took place, these strains are referred to as Ebola/Zaire (EBOZ), Ebola/Sudan (EBOS), and Ebola/Tai Forest (EBOT). A fourth Ebola strain, called Ebola/Reston(EBOR), has not been found to cause disease in humans. As outbreaks of Ebola hemorrhagic fever continue to occur, other strains may be identified. The viruses are long rods, 800 to 1000 nanometers (nm) long (1 nm equals one-billionth of a meter, or 4 x 10-8 in), but particles as long as 14,000 nm have been seen. Each virus consists of a coiled strand of ribonucleic acid (RNA) contained in an envelope derived from the host cell membrane that is covered with 7 nm spikes placed 10 nm apart visible on the surface of the virion (Figure 1). When magnified several thousand times by an electron microscope, these viruses have the appearance of long filaments or threads but the particles are pleomorphic, meaning they can exist in many shapes. Their basic structure is long and filamentious, essentially bacilliform, but the viruses often takes on a "U" shape (Figure 2). They contain a unique single-stranded molecule of noninfectious (negative sense ) RNA. The virus is composed of 7 polypeptides, a nucleoprotein, a glycoprotein, a polymerase and 4 other undesignated proteins. Proteins are produced from polyadenylated monocistronic mRNA a species transcribed from vi genomes. As the infection progresses the cytoplasm of the infected cell develops "prominent inclusion bodies" which contains the viral nucelocapsid, which will become highly structured. The virus then assembles, and buds off the host cell, attaining its lipoprotein coat from the infected cell's outer membrane. The replication in and destruction of the host cell is rapid and produces a large number of viruses budding from the cell membrane. Symptoms Cases of Ebola have occurred in isolated instances and in outbreaks in sub-Saharan Africa. A significant problem in diagnosing the disease is that the viruses often strike in remote areas of developing countries, where access to laboratories for specimen analysis is limited. Of all the Ebola strains, Ebola/Zaire is the most dramatic and deadly. The Ebola virus causes hemorrhagic fever, which is characterized by such symptoms as severe headache, weakness, and muscle aches, followed by vomiting, abdominal pain, diarrhea, inflammation of the throat (pharyngitis), inflammation of the mucous membranes in the eye (conjunctivitis), and bleeding from body openings. The virus spreads through the blood and is replicated in many organs. The histopathologic change is focal necrosis in these organs, including the liver, lymphatic organs, kidneys, ovaries and testes. The central lesions appear to be those affecting the vascular endothelium and the platelets. The resulting manifestations are bleeding, especially in the muc usually seven to ten days. The mortality rates in the known outbreaks have been 60 percent with Ebola/Sudan virus and 77 to 88 percent with Ebola/Zaire virus. 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. There are no proven therapeutic drugs to treat Ebola hemorrhagic fever, and treatment currently consists of preventing shock and providing supportive care. Medical care is complicated by the need to protect medical and nursing personnel. Convalescence is slow, often taking five weeks or more, and is marked by weight loss and amnesia in the early stages of recovery. Currently, there is little hope of developing a vaccine against the Ebola virus. Near the end of one outbreak in Zaire during 1995, blood from convalescent patients was transfused into severely ill victims in an attempt to transfer antibodies and T-lymphocytes (one type of white blood cell) that might neutralize the Ebola virus and destroy infected cells. This procedure met with some success, but carefully controlled trials must be conducted to confirm the safety and effectiveness of this method. Evolution Besides morphological and biochemical similarities, all nonsegmented negative-strand RNA viruses share several features in their mechanisms of transcription and replication: similar genome organization, complementarity of the genome extremities, homologous sequences in the 3' untranslated region, conserved transcriptional signals, interruption of genes by intergenic sequences, possession of a virion-associated polymerase, helical nucleocapsid as the functional template for synthesis of replicative and messenger RNA, replication by synthesis of a full-length antigenome, transcription of messenger RNAs by sequential interrupted synthesis from a single promotor, transcription and replication in the cytoplasm, and maturation by envelopment of independently assembled nucleocapsids at membrane sites containing inserted viral proteins. These data suggest that all nonsegmented negative-strand RNA viruses are derived from a common progenitor and support the classification of the families Filoviridae, Paramyxoviridae and Rhabdoviridae in the order Mononegavirales . In addition, comparative amino acid sequence analyses of nucleoproteins and polymerase proteins suggest that filoviruses are more closely related to paramyxoviruses than to rhabdoviruses. History of Ebola Outbreaks Ebola virus was identified for the first time in 1976, when two epidemics of hemorrhagic fever occurred, one in Zaire, the other 600 km distant in Sudan. The combined outbreaks accounted for more than 550 cases and 430 deaths. A third strain of the Ebola virus was identified in 1989 in a quarantine facility in Reston, Virginia, where hundreds of imported Philippine monkeys died. The Ebola/Reston virus seems not to cause disease in humans-although four laboratory technicians were infected with the virus, none of them became ill. Another large epidemic of Ebola hemorrhagic fever occurred in Zaire, this time in and around the city of Kikwit during the summer of 1995, infecting 315 people and killing 242. The strains of Ebola virus isolated in Zaire in 1976 and 1995, 19 years and 500 km apart, are virtually identical. A single nonfatal case of Ebola hemorrhagic fever occurred in late 1994 in Cte d'Ivoire. A Swiss zoologist who performed an autopsy on a chimpanzee was infected by the virus, which was subsequently identified as the fourth strain, Ebola/Tai Forest, named for the Tai Forest in the Cte d'Ivoire. Since the first episode there have been additional cases and fatalities