Ebola virus (/ɛˈboʊlə/; EBOV, formerly designated Zaire ebolavirus) is one of five known viruses within the genus Ebolavirus. Four of the five known ebola viruses, including EBOV, cause a severe and often fatal hemorrhagic fever in humans and other mammals, known as Ebola virus disease (EVD). Ebola virus has caused the majority of human deaths from EVD, and is the cause of the 2013–2015 Ebola virus epidemic in West Africa, which has resulted in at least 27,678 suspected cases and 11,276 confirmed deaths.
Ebola virus and its genus were both originally named for Zaire (now the Democratic Republic of Congo), the country where it was first described, and was at first suspected to be a new "strain" of the closely related Marburg virus.The virus was renamed "Ebola virus" in 2010 to avoid confusion. Ebola virus is the single member of the species Zaire ebolavirus, which is the type species for the genus Ebolavirus, family Filoviridae, order Mononegavirales. The natural reservoir of Ebola virus is believed to be bats, particularly fruit bats, and it is primarily transmitted between humans and from animals to humans through body fluids.
The EBOV genome is a single-stranded RNA approximately 19,000 nucleotides long. It encodes seven structural proteins: nucleoprotein (NP), polymerase cofactor (VP35), (VP40), GP, transcription activator (VP30), VP24, and RNA-dependent RNA polymerase (L).
Because of its high mortality rate (up to 83-90%),[9][10] EBOV is also listed as a select agent, World Health Organization Risk Group 4 Pathogen (requiring Biosafety Level 4-equivalent containment), a U.S. National Institutes of Health/National Institute of Allergy and Infectious Diseases Category A Priority Pathogen, U.S. CDC Centers for Disease Control and Prevention Category A Bioterrorism Agent, and listed as a Biological Agent for Export Control by the Australia Group
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EBOV carries a negative-sense RNA genome in virions that are cylindrical/tubular, and contain viral envelope, matrix, and nucleocapsid components. The overall cylinders are generally approximately 80 nm in diameter, and have a virally encoded glycoprotein (GP) projecting as 7-10 nm long spikes from its lipid bilayer surface.The cylinders are of variable length, typically 800 nm, but sometimes up to 1000 nm long. The outer viral envelope of the virion is derived by budding from domains of host cell membrane into which the GP spikes have been inserted during their biosynthesis.[citation needed] Individual GP molecules appear with spacings of about 10 nm.[citation needed] Viral proteins VP40 and VP24 are located between the envelope and the nucleocapsid (see following), in the matrix space. At the center of the virion structure is the nucleocapsid, which is composed of a series of viral proteins attached to an 18–19 kb linear, negative-sense RNA without 3′-polyadenylation or 5′-capping (see following);[citation needed] the RNA is helically wound and complexed with the NP, VP35, VP30, and L proteins;[13][better source needed] this helix has a diameter of 80 nm and contains a central channel of 20–30 nm in diameter.
The overall shape of the virions after purification and visualization (e.g., by ultracentrifugation and electron microscopy, respectively) varies considerably; simple cylinders are far less prevalent than structures showing reversed direction, branches, and loops (e.g., U-, shepherd's crook-, 9- or eye bolt-shapes, or other or circular/coiled appearances), the origin of which may be in the laboratory techniques applied.The characteristic "threadlike" structure is, however, a more general morphologic characteristic of filoviruses (alongside their GP-decorated viral envelope, RNA nucleocapsid, etc.)
Each virion contains one molecule of linear, single-stranded, negative-sense RNA, 18,959 to 18,961 nucleotides in length. The 3′ terminus is not polyadenylated and the 5′ end is not capped. This viral genome codes for seven structural proteins and one non-structural protein. The gene order is 3′ – leader – NP – VP35 – VP40 – GP/sGP – VP30 – VP24 – L – trailer – 5′; with the leader and trailer being non-transcribed regions, which carry important signals to control transcription, replication, and packaging of the viral genomes into new virions. Sections of the NP, VP35 and the L genes from filoviruses have been identified as endogenous in the genomes of several groups of small mammals.
It was found that 472 nucleotides from the 3' end and 731 nucleotides from the 5' end are sufficient for replication of a viral "minigenome", though not sufficient for infection. The minigenome's genetic material by itself is not infectious, because viral proteins, among them the RNA-dependent RNA polymerase, are necessary to transcribe the viral genome into mRNAs because it is a negative sense RNA virus, as well as for replication of the viral genome.
Recent advances in genomic technologies have been applied to the analysis of blood samples from those infected in the 2014 outbreak. A massively parallel viral sequencing of genetic material collected from 78 patients with confirmed Ebola virus disease, representing more than 70% of cases diagnosed in Sierra Leone from late May to mid-June, 2014 was carried out. This work provided near–real-time insights into the transmission dynamics and genetic evolution, shedding light on the origins of the virus causing the 2014 outbreak in West Africa, and whether the 2014 outbreak is still being fed by new contacts with its natural reservoir (no such evidence was found). As is typical of RNA-coded viruses, the Ebola virus was found to mutate rapidly, both within a person during the progression of disease and in the reservoir among the local human population The observed mutation rate of 2.0 x 10−3 substitutions per site per year is as fast as that of seasonal influenza. This is likely to represent incomplete purifying selection as the virus is repeatedly passed from human to human, and may pose challenges for the development of a vaccine to the virus
Ebola virus is one of the four ebolaviruses known to cause disease in humans. It has the highest case-fatality rate of these ebolaviruses, averaging 83 percent since the first outbreaks in 1976, although fatality rates up to 90 percent have been recorded in one outbreak (2002–03). There have also been more outbreaks of Ebola virus than of any other ebolavirus. The first outbreak occurred on 26 August 1976 in Yambuku. The first recorded case was Mabalo Lokela, a 44‑year-old schoolteacher. The symptoms resembled malaria, and subsequent patients received quinine. Transmission has been attributed to reuse of unsterilized needles and close personal contact, body fluids and places where the person has touched.
During the 1976 Ebola outbreak in Zaire, Ngoy Mushola travelled from Bumba to Yambuku, where he recorded the first clinical description of the disease in his daily log:
"The illness is characterized with a high temperature of about 39°C, hematemesis, diarrhea with blood, retrosternal abdominal pain, prostration with "heavy" articulations, and rapid evolution death after a mean of three days."
Since the first recorded clinical description of the disease during 1976 in Zaire, the recent Ebola outbreak that started in March 2014, in addition, has reached epidemic proportions and has killed more than 8000 persons as of January 2015. This outbreak has been centered in West Africa, an area that had not previously been affected by the disease. The toll has been particularly grave in three countries: Guinea, Liberia, and Sierra Leone. A few cases have also been reported in countries outside of West Africa, all related to international travelers who were exposed in the most affected regions and later showed symptoms of Ebola fever after reaching their destinations.
The severity of the disease in humans varies widely, from rapid fatality to mild illness or even asymptomatic response. Studies of outbreaks in the late twentieth century failed to find a correlation between the disease severity and the genetic nature of the virus. Hence the variability in the severity of illness was suspected to correlate with genetic differences in the victims. This has been difficult to study in animal models that respond to the virus with hemorrhagic fever in a similar manner as humans, because typical mouse models do not so respond, and the required large numbers of appropriate test subjects are not easily available. In late October 2014, a publication reported a study of the response to a mouse-adapted strain of Zaire ebolavirus presented by a genetically diverse population of mice that was bred to have a range of responses to the virus that includes fatality from hemorrhagic fever. It was found that the wide range of these rodents' responses to this single virus genotype mimics that of humans to the wild virus, suggesting that genetic differences among the victims is key. The much more detailed study of the response that is possible in an animal model is expected to result in the identification of genes that control the response to the virus.
Ebola virus was first identified as a possible new "strain" of Marburg virus in 1976. At the same time, a third team introduced the name "Ebola virus", derived from the Ebola River where the 1976 outbreak occurred.The International Committee on Taxonomy of Viruses (ICTV) identifies Ebola virus as species Zaire ebolavirus, which is included into the genus Ebolavirus, family Filoviridae, order Mononegavirales. The name "Ebola virus" is derived from the Ebola River—a river that was at first thought to be in close proximity to the area in Democratic Republic of Congo, previously called Zaire, where the 1976 Zaire Ebola virus outbreak occurred—and the taxonomic suffix virus.
In 2000, the virus name was changed to Zaire Ebola virus, and in 2002 to species Zaire ebolavirus. However, most scientific articles continued to refer to "Ebola virus" or used the terms Ebola virus and Zaire ebolavirus in parallel. Consequently, in 2010, a group of researchers recommended that the name "Ebola virus" be adopted for a subclassification within the species Zaire ebolavirus, with the corresponding abbreviation EBOV.[1] Previous abbreviations for the virus were EBOV-Z (for Ebola virus Zaire) and ZEBOV (for Zaire Ebola virus or Zaire ebolavirus). In 2011, the ICTV explicitly rejected a proposal (2010.010bV) to recognize this name, as ICTV does not designate names for subtypes, variants, strains, or other subspecies level groupings.At present, ICTV does not officially recognize "Ebola virus" as a taxonomic rank, and rather continues to use and recommend only the species designation Zaire ebolavirus.
The prototype Ebola virus, variant Mayinga (EBOV/May), was named for Mayinga N'Seka, a nurse who died during the 1976 Zaire outbreak.
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