Ebola viruses

The ebolaviruses are filoviruses that cause Ebola virus disease, a severe and frequently fatal illness dominated by profound fluid loss, shock and multi-organ failure rather than by the dramatic bleeding the older name, Ebola haemorrhagic fever, implies. It belongs to the genus Orthoebolavirus, one of the two filovirus genera that infect humans alongside the marburgviruses. The genus contains six species, of which four cause human disease (Ebola, Sudan, Bundibugyo and Taï Forest viruses), while Reston virus is non-pathogenic in people and Bombali virus is known only from bats.

The name derives from the Ebola River near Yambuku, the northern Zairean village at the centre of the first recognised outbreak in 1976. For decades the virus caused sporadic, terrifying but geographically contained outbreaks in Central Africa. That changed with the 2013 to 2016 West African epidemic, which produced roughly 28,600 cases and 11,300 deaths, showed that Ebola could sustain itself in dense urban populations, and drove the licensing of the first vaccines and treatments.

Ebola disease remains a live public-health emergency. At the time of writing a Bundibugyo virus outbreak in the Democratic Republic of the Congo and Uganda has been declared a Public Health Emergency of International Concern, a reminder that the licensed countermeasures are specific to the Zaire species and leave the others largely uncovered.

Discovery and historical significance

Ebola virus was discovered in 1976 during two nearly simultaneous outbreaks: one at the Yambuku mission hospital in northern Zaire, the other at Nzara in southern Sudan. Investigators including Peter Piot and the team around Karl Johnson at the United States Centers for Disease Control isolated a new filamentous virus resembling Marburg, identified nine years earlier, but antigenically distinct. The two 1976 outbreaks, initially assumed to share a source, were later shown to be caused by two different viruses, now called Ebola virus and Sudan virus. Reuse of unsterilised needles at Yambuku amplified the outbreak and gave an early, stark lesson in health-care transmission.

Subsequent decades defined the genus. Reston virus was recognised in 1989 in macaques imported to a primate facility in Reston, Virginia, and proved able to infect people without causing illness. Taï Forest virus caused a single non-fatal human infection in an ethologist who performed a chimpanzee necropsy in Côte d’Ivoire in 1994. Bundibugyo virus emerged in Uganda in 2007. In 2018, Bombali virus was identified in insectivorous bats in Sierra Leone, the first ebolavirus characterised entirely from its animal host before any human case.

The defining event was the West African epidemic of 2013 to 2016. Beginning in Guinea and spreading through Sierra Leone and Liberia, it dwarfed every previous outbreak combined, reached several continents through travel, and transformed Ebola from a rare curiosity into a global-health priority. It also generated the clinical cohorts and field-trial infrastructure that produced the ring-vaccination trial of the rVSV vaccine and, in the subsequent Democratic Republic of the Congo outbreaks, the randomised trial of monoclonal-antibody therapy.

Classification, structure, and genome

Classification

Ebola virus belongs to the family Filoviridae, order Mononegavirales, and to the genus Orthoebolavirus (renamed from Ebolavirus under the 2023 revision that also introduced binomial species names). The sister genus Orthomarburgvirus contains Marburg and Ravn viruses. The genus Orthoebolavirus holds six species, distinguished by genome sequence, geography, host range and pathogenicity.

Ebolavirus species and their medical importance

Species (ICTV)	Virus (abbreviation)	First recognised	Geographic focus	Human disease	Representative case fatality
Orthoebolavirus zairense	Ebola virus (EBOV)	1976, Yambuku (then Zaire)	Central and West Africa	Severe, epidemic	~40% to ~90%
Orthoebolavirus sudanense	Sudan virus (SUDV)	1976, Nzara (South Sudan)	East and Central Africa	Severe, epidemic	~40% to ~70%
Orthoebolavirus bundibugyoense	Bundibugyo virus (BDBV)	2007, Bundibugyo (Uganda)	Uganda and neighbouring DRC	Severe, epidemic	~25% to ~40%
Orthoebolavirus taiense	Taï Forest virus (TAFV)	1994, Taï Forest (Côte d’Ivoire)	West Africa	Single non-fatal case	Not established
Orthoebolavirus restonense	Reston virus (RESTV)	1989, from Philippine macaques	Southeast Asia	None (silent seroconversion)	Nil in humans
Orthoebolavirus bombaliense	Bombali virus (BOMV)	2018, Sierra Leone (bats)	African bats	None known	Not established

The single term “Ebola virus” properly denotes the species Orthoebolavirus zairense, the type species and the cause of most large outbreaks. In everyday speech “Ebola” is used loosely for the whole group, but the species distinction matters clinically because the licensed vaccines and antibody treatments protect only against Zaire ebolavirus.

Virion structure

Filoviruses are among the most distinctive-looking of all viruses: long, thread-like enveloped filaments of uniform 80 nanometre diameter but highly variable length, frequently bent into U-shapes, 6-shapes or rings. Within the envelope lies a helical ribonucleocapsid: the RNA genome wrapped in nucleoprotein and associated with VP35, VP30, VP24 and the large (L) polymerase. VP40, the matrix protein, forms the layer beneath the envelope and is the main structural organiser of the particle. The envelope carries trimers of the surface glycoprotein, GP1,2, whose heavily glycosylated mucin-like domain shields the underlying protein from neutralising antibody.

Genome organisation

The genome is a single molecule of negative-sense, non-segmented RNA of about 19 kilobases, the largest of any negative-strand RNA virus. Seven genes are arranged in the fixed order 3’-NP-VP35-VP40-GP-VP30-VP24-L-5’. Because transcription proceeds from the 3’ end and the polymerase progressively falls off between genes, genes nearest the 3’ end (NP) are transcribed most abundantly and those nearest the 5’ end (L) least, giving a built-in gradient of protein expression.

The glycoprotein gene is the genus’s most striking feature. Its primary product is not the surface spike but a secreted glycoprotein (sGP), an immune decoy released in large amounts. The full-length structural glycoprotein GP1,2 is made only when the polymerase stutters at a run of seven uridine residues and inserts an extra adenosine, shifting the reading frame; a third frame yields a smaller secreted form. GP1,2 is then cleaved by the cellular protease furin into the receptor-binding GP1 and the fusion subunit GP2. Marburg virus, by contrast, encodes a single glycoprotein and makes no sGP, one of several biological differences between the two genera.

Replication cycle

Ebola virus follows the canonical arc of a non-segmented negative-strand RNA virus (attachment, entry, uncoating, gene expression and genome replication, assembly and release), with an unusual endosomal entry step.

Attachment is promiscuous: rather than a single specific receptor, the glycoprotein exploits host lectins such as DC-SIGN, phosphatidylserine on the virion surface, and the phosphatidylserine receptors TIM-1 and the TAM-family kinase Axl. This breadth helps explain the wide cell tropism. The bound virion is then internalised by macropinocytosis, a bulk-uptake process, rather than by classical receptor-mediated endocytosis.

Inside the acidifying endosome, host cathepsin proteases (B and L) trim the glycoprotein, removing the glycan cap and mucin-like domain to expose the receptor-binding head. Only then can GP1 bind its true receptor, the lysosomal cholesterol transporter Niemann-Pick C1 (NPC1). This intracellular receptor is essential: cells and animals lacking functional NPC1 are resistant to infection, which makes the GP1 to NPC1 interaction a prime antiviral target. Receptor engagement triggers GP2-mediated fusion of the viral and endosomal membranes, releasing the nucleocapsid into the cytoplasm.

All subsequent steps occur in the cytoplasm. The L polymerase, with its cofactor VP35 and the transcription activator VP30, first transcribes the genes into messenger RNAs and then, once nucleoprotein is abundant, switches to replicating full-length antigenome and genome copies. Newly made nucleocapsids are transported to the plasma membrane, where VP40 drives budding by recruiting the host ESCRT machinery, pinching off progeny filaments that carry the glycoprotein spikes. VP40 is sufficient on its own to form and release empty particles, underscoring its central structural role.

Pathogenesis

Ebola virus is a pathogen of the innate immune system before it is anything else. Its first targets are the mononuclear phagocytes and dendritic cells that patrol the site of entry. Infected macrophages release a flood of pro-inflammatory cytokines and tissue factor, while infected dendritic cells fail to mature and so cannot prime an effective adaptive response. These cells also disseminate the virus through the lymphatics and blood to the liver, spleen, adrenal glands and endothelium.

Central to this is the virus’s suppression of interferon, the body’s front-line antiviral alarm. VP35 masks double-stranded RNA and blocks the sensor RIG-I, preventing interferon from being made, while VP24 blocks the nuclear import of STAT1, preventing cells from responding to whatever interferon is produced. (Marburg virus achieves the same end by different means, using VP40 to disable the JAK-STAT pathway, a mechanistic divergence between the genera.) The result is unchecked early replication.

The coagulopathy that gives the disease its old name is a consequence of this inflammatory storm rather than a primary bleeding defect. Tissue factor released from infected and activated macrophages triggers disseminated intravascular coagulation (DIC), consuming clotting factors and platelets, so that when bleeding occurs it reflects consumptive coagulopathy and thrombocytopenia. Even so, overt haemorrhage is present in a minority of patients and is rarely the cause of death.

Lymphopenia is a paradoxical hallmark: although lymphocytes are not themselves infected, huge numbers of them die by bystander apoptosis, stripping the host of the T cells needed to clear the virus. Damage to the adrenal cortex impairs the blood-pressure response and worsens shock. The clinical picture that emerges, of vasodilatation, capillary leak, fluid loss and organ failure, is closer to severe sepsis than to a classical bleeding diathesis. Survival tracks closely with the ability to mount an antibody response: survivors develop IgM and IgG against the virus, whereas those who die often fail to seroconvert.

Epidemiology

Ebola disease is a zoonosis of sub-Saharan Africa. Each species has a characteristic geography: Zaire ebolavirus in Central and, since 2013, West Africa; Sudan virus in Uganda and South Sudan; Bundibugyo virus in the Uganda to Democratic Republic of the Congo border region; Taï Forest virus in West Africa. Reston virus circulates in the Philippines and China in pigs and macaques without causing human illness.

The natural reservoir is not settled. Marburg virus has a confirmed reservoir in the Egyptian rousette fruit bat, but for the ebolaviruses the reservoir remains unproven: viral RNA and antibodies have been found in several fruit-bat species, and outbreaks are epidemiologically linked to bats and to contact with infected great apes and forest antelope, yet no infectious ebolavirus has been reproducibly isolated from a wild bat. Spillover to humans is genuinely rare, which is why outbreaks are sporadic and often begin with a single index case.

Human-to-human spread then occurs by direct contact with blood or body fluids (blood, vomitus, stool, saliva, sweat, breast milk, semen and tears) or with contaminated surfaces. Patients are not infectious during the incubation period and become progressively more infectious as viral load rises, so the sickest patients and freshly deceased bodies are the most dangerous sources. Transmission is powerfully amplified in two settings: health-care facilities without adequate protective equipment, and traditional funerals involving washing and touching the body. The West African epidemic showed that once these amplifiers combine with an urban population, an outbreak can grow explosively; the basic reproduction number in that setting was estimated at around 1.5 to 2.

Case fatality varies by species and, critically, by the standard of care. Zaire ebolavirus has historically killed from around 40% to as high as 90% of those infected, Sudan virus somewhat less, and Bundibugyo virus less again. These figures fall substantially where early, intensive supportive care and specific therapy are available.

Natural history

After an incubation period of 2 to 21 days, most commonly 6 to 10 days, illness begins abruptly. The exposure route and dose influence the interval only modestly. The untreated course then moves through recognisable phases. A non-specific febrile prodrome of fever, profound fatigue, muscle pain and headache lasts a few days and is clinically indistinguishable from malaria or many other tropical fevers.

Around the fifth day of illness a gastrointestinal phase supervenes, with vomiting and copious watery diarrhoea that can reach several litres a day, producing rapid volume depletion. In patients who deteriorate, the second week brings hypovolaemic and distributive shock, metabolic acidosis, and multi-organ dysfunction affecting the kidneys, liver and, ultimately, the brain. Death, when it occurs, is usually between days 7 and 12 and results from shock and organ failure.

Patients who survive typically begin to improve from around day 10 as an antibody response takes hold and viral load falls. Convalescence is slow and often complicated by a post-Ebola syndrome of arthralgia, ocular disease, hearing loss and fatigue. Because the virus can persist in immune-privileged sites after clearance from blood, a small number of survivors experience late relapse or become a source of renewed transmission months later.

Clinical presentations and complications

The early illness is a non-specific febrile syndrome. Fever, intense asthenia, myalgia, arthralgia and headache predominate, and in an endemic setting the overwhelming diagnostic difficulty is that this picture is far more often malaria, typhoid or another common infection than Ebola. A history of contact with a sick or deceased person, with a known chain of transmission, or with bats or bushmeat is what raises suspicion.

The peak of illness is dominated by the gastrointestinal phase. Vomiting and high-volume secretory diarrhoea cause the fluid and electrolyte losses that drive the disease: hypovolaemia, hypotension, hypokalaemia and hyponatraemia, with third-spacing and facial oedema. This is why modern management frames Ebola as a disease of fluid resuscitation more than of haemorrhage control. Conjunctival injection, hiccups, a maculopapular rash and abdominal pain are common.

Haemorrhagic manifestations, when present, are usually a late and ominous sign: oozing from venepuncture sites, petechiae, epistaxis, gastrointestinal bleeding and mucosal haemorrhage. They occur in a minority of patients and reflect coagulopathy and thrombocytopenia rather than a discrete bleeding organ. Progression to severe disease brings acute kidney injury, marked transaminase elevation from hepatic involvement, and central-nervous-system features ranging from encephalopathy to seizures, sometimes with virus detectable in cerebrospinal fluid. Across outbreaks, the admission viral load is the most consistent predictor of death, with kidney injury and neurological signs marking a poor prognosis.

Survivors face a distinct set of complications. Persistent arthralgia, myalgia, headache, ocular problems and hearing loss make up the post-Ebola syndrome. Uveitis can appear weeks after recovery and is associated with virus persisting in the aqueous humour of the eye even when blood is clear. Rarely, virus persisting in the central nervous system causes a late relapse with meningoencephalitis, and virus persisting in the male genital tract can be transmitted sexually months after recovery.

Diagnosis

Because early Ebola disease cannot be distinguished clinically from common febrile illnesses, diagnosis rests on laboratory confirmation coupled with an epidemiological case definition. Reverse transcription polymerase chain reaction (RT-PCR) detecting viral RNA in blood is the diagnostic standard, becoming positive at or shortly after the onset of symptoms and rising with disease severity. A negative test very early in a symptomatic contact may need repeating after 48 to 72 hours, because viraemia can lag the first symptoms.

Antigen-detection rapid diagnostic tests, which need no cold chain or instrumentation, support triage and field screening, though they are less sensitive than RT-PCR. Serology has a secondary role: IgM antibodies appear in the second week and IgG somewhat later, useful for retrospective diagnosis and survivor studies but not for the acute decision to isolate and treat. Virus isolation in cell culture is definitive but is performed only in a small number of maximum-containment laboratories.

The laboratory hazard shapes everything. Live Ebola virus is a biosafety level 4 (BSL-4) agent, so isolation and any procedure that could generate infectious aerosol are confined to maximum-containment facilities. Routine diagnostic work is done on inactivated samples or within closed molecular platforms, and even basic clinical-pathology testing on a suspected case demands strict biosafety precautions.

Management

The transformation in Ebola care over the last decade has two parts, and the first matters more than the second. Aggressive supportive care is the foundation of treatment: early and generous repletion of fluid and electrolytes to match gastrointestinal losses, correction of hypokalaemia and hypovolaemia, and support of failing organs. Rigorous supportive care alone lowers mortality substantially, and it is available even where specific drugs are not.

Specific therapy has arrived, but only for one species. The PALM randomised controlled trial, conducted during the 2018 to 2020 Democratic Republic of the Congo outbreak, tested four agents against Zaire ebolavirus and established the superiority of two monoclonal-antibody products. Mortality was 35.1% with the single antibody ansuvimab (mAb114) and 33.5% with the triple-antibody combination REGN-EB3, against roughly 50% with the earlier agent ZMapp, with the greatest benefit in patients treated early and with a low viral load. Both are now licensed.

Ebola disease therapeutics

Agent	Type	Target	Status
Inmazeb (atoltivimab, maftivimab, odesivimab; REGN-EB3)	Triple monoclonal antibody	Zaire glycoprotein	Licensed 2020 (Zaire only)
Ebanga (ansuvimab; mAb114)	Single monoclonal antibody	Zaire glycoprotein	Licensed 2020 (Zaire only)
Remdesivir	Nucleotide-analogue antiviral	Viral polymerase	Investigational; under trial in current outbreaks
MBP134	Pan-ebolavirus monoclonal antibody pair	Conserved glycoprotein epitopes	Investigational; prioritised for Sudan and Bundibugyo disease

The species gap is the central clinical problem. Neither licensed antibody protects against Sudan or Bundibugyo virus, because both target the Zaire glycoprotein. For the current Bundibugyo outbreak, the World Health Organization has prioritised the broadly reactive antibody pair MBP134, the antibody maftivimab and the antiviral remdesivir for clinical trials in confirmed cases, and combination antibody-plus-remdesivir regimens are being evaluated. Until such trials report, care for the non-Zaire species is supportive with investigational agents used under trial protocols.

Prevention and public health

Vaccination

Two vaccines are licensed, and both protect only against Zaire ebolavirus. Ervebo (rVSV-ZEBOV) is a single-dose, live recombinant vesicular stomatitis virus carrying the Zaire glycoprotein; it was prequalified by the World Health Organization in 2019 after a ring-vaccination trial showed high protective efficacy, and it is used reactively around cases and to protect health and frontline workers. The second is a two-dose prophylactic regimen, Zabdeno (Ad26.ZEBOV) followed 56 days later by Mvabea (MVA-BN-Filo), prequalified in 2021 and suited to pre-emptive protection of at-risk populations rather than to rapid outbreak use.

There is no licensed vaccine against Sudan, Bundibugyo or Marburg. Candidate vaccines against Sudan and Marburg (including adenovirus-vectored and recombinant vesicular stomatitis virus platforms) have advanced into clinical trials and have been deployed experimentally during recent outbreaks, but none has yet been licensed, which is why the current Bundibugyo emergency has no vaccine of proven efficacy against the causative species.

Infection prevention and control

Because there is no environmental or vector route, transmission is interrupted by breaking body-fluid contact. Care of a suspected or confirmed case demands full personal protective equipment, single-room isolation, and rigorous decontamination, with particular attention to procedures that generate splashes or aerosols. Safe and dignified burial, which removes the highly infectious corpse from traditional washing rituals, is one of the most effective single interventions. Laboratory samples are handled as maximum-hazard material.

Post-exposure prophylaxis

Ring vaccination with Ervebo functions as a form of reactive prophylaxis, immunising the contacts and contacts-of-contacts around a Zaire ebolavirus case to build a protective barrier; the vaccine’s rapid onset of immunity underpins this use. For high-risk percutaneous or mucosal exposures, monoclonal-antibody therapy and vaccination have been used pre-emptively under expert guidance, though the evidence base for post-exposure drug prophylaxis is limited.

Surveillance and notification

Ebola disease is subject to the International Health Regulations and is reportable as a matter of international concern. Rapid case detection, laboratory confirmation, contact tracing with 21-day follow-up matched to the incubation period, and coordinated outbreak response are the core public-health tools. The current Bundibugyo outbreak has been declared a Public Health Emergency of International Concern, triggering enhanced international surveillance and response.

Outbreak response

Control combines case finding and isolation in dedicated treatment units, contact tracing, ring vaccination where a species-matched vaccine exists, safe burial, community engagement to counter mistrust, and cross-border coordination. The scale of the West African epidemic showed that late or fragmented responses allow exponential growth, whereas early case isolation and vaccination can contain an outbreak within a few transmission chains.

South African context

South Africa has never had an indigenous Ebola outbreak, and the ebolaviruses are not endemic to the country, but it carries a recognised importation risk through travel and its role as a regional medical-referral hub. The country’s single documented Ebola importation occurred in 1996, when a physician infected while treating patients in Gabon travelled to Johannesburg, where a nurse who cared for him contracted the virus and died, a stark illustration of health-care transmission from an unrecognised case.

Ebola disease is a Category 1 Notifiable Medical Condition, requiring immediate reporting on clinical suspicion, and definitive testing is centralised at the National Institute for Communicable Diseases, which houses the country’s specialised high-containment diagnostic capability. Suspected cases are managed along a defined pathway of isolation, senior consultation and specialised laboratory referral rather than routine testing; the operational detail of case definitions, specimen packaging, notification and the domestic response is set out in the national viral haemorrhagic fever guidance. Preparedness has been reinforced during the current regional Bundibugyo emergency, for which no vaccine of proven efficacy against the causative species is available.

References and recommended reading

• Kuhn JH, Amarasinghe GK, Perry DL. Filoviridae. In: Fields Virology, 7th edition. Philadelphia: Wolters Kluwer; 2023. The primary reference for filovirus classification, structure, replication and pathogenesis used throughout this profile.
• Bray M, Chertow DS. Viral Hemorrhagic Fevers. In: Richman DD, Whitley RJ, Hayden FG (eds.), Clinical Virology, 4th edition. Washington: ASM Press; 2016. Source for the clinical course, the primacy of fluid loss over haemorrhage, and outbreak epidemiology.
• Burrell CJ, Howard CR, Murphy FA. Fenner and White’s Medical Virology, 5th edition. London: Academic Press; 2017. The concise foundational account of filovirus virology and transmission.
• Mulangu S, Dodd LE, Davey RT Jr, et al. A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics. N Engl J Med. 2019;381(24):2293-2303. The PALM trial; the source for the survival benefit of ansuvimab and REGN-EB3.
• Florez-Alvarez L, de Souza EE, Botosso VF, et al. Hemorrhagic fever viruses: pathogenesis, therapeutics, and emerging and re-emerging potential. Front Microbiol. 2022;13:1040093. Current review of filovirus pathophysiology and the vaccine and antibody landscape.
• World Health Organization. Ebola disease caused by Bundibugyo virus, Democratic Republic of the Congo and Uganda (Disease Outbreak News and PHEIC determination). Geneva: WHO; 2026. Source for the current outbreak status and prioritised investigational countermeasures.