Ebola virus

Zaire ebolavirus, more commonly known as simply Ebola virus (EBOV), is one of six known species within the genus Ebolavirus. Four of the six known ebolaviruses, 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 2013–2016 Ebola virus epidemic in West Africa, which resulted in at least 28,646 suspected cases and 11,323 confirmed deaths. 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. Zaire ebolavirus, more commonly known as simply Ebola virus (EBOV), is one of six known species within the genus Ebolavirus. Four of the six known ebolaviruses, 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 2013–2016 Ebola virus epidemic in West Africa, which resulted in at least 28,646 suspected cases and 11,323 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 members of the species are called Zaire ebolaviruses. 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%), EBOV is also listed as a select agent, World Health Organization Risk Group 4 Pathogen (requiring Biosafety Level 4-equivalent containment), a US National Institutes of Health/National Institute of Allergy and Infectious Diseases Category A Priority Pathogen, US CDC Centers for Disease Control and Prevention Category A Bioterrorism Agent, and a Biological Agent for Export Control by the Australia Group. 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. Individual GP molecules appear with spacings of about 10 nm. 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); the RNA is helically wound and complexed with the NP, VP35, VP30, and L proteins; this helix has a diameter of 80 nm. 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. Virus sequencing 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, provided evidence that the 2014 outbreak was no longer being fed by new contacts with its natural reservoir. Using third-generation sequencing technology, investigators were able to sequence samples as quickly as 48 hours. Like other RNA viruses, Ebola virus mutates 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.