Genus: Ebolavirus

Genus: Ebolavirus

Distinguishing features

Three ebolaviruses (Bundibugyo virus [BDBV], Ebola virus [EBOV], and Sudan virus [SUDV]) are highly lethal human pathogens. Taï Forest virus (TAFV) has caused a single recorded case of severe but nonlethal human disease. Reston virus (RESTV) has, as far as is known, only caused one inapparent human infection. The pathogenicity of Bombali virus (BOMV) for humans is unclear (Kuhn et al., 2020). Ebolaviruses are notable for encoding three distinct proteins from their glycoprotein (GP) genes, a strategy they share with cuevaviruses (Negredo et al., 2011, Sanchez et al., 1996, Volchkov et al., 1995).



Virions are filamentous in shape, but can also be branched, circular, U-shaped, or 6‑shaped. Spherical forms are rare to absent (Figure 1.Ebolavirus). Virions vary greatly in length (>20 μm) but have a diameter of 96–98 nm. Peak infectivity has been associated with particles of about 805 nm in length (Beniac et al., 2012, Ellis et al., 1979a, Ellis et al., 1979b, Geisbert and Jahrling 1995, Ryabchikova and Price 2004).

Virions are composed of a central core formed by a helical ribonucleoprotein (RNP) complex, surrounded by matrix layer and a lipid envelope derived from the host cell plasma membrane. Polyploidy has been observed. Spikes about 7 nm in diameter and spaced at intervals of about 10 nm are seen as globular structures on the surface of virions (Beniac et al., 2012, Geisbert and Jahrling 1995, Ryabchikova and Price 2004, Sugita et al., 2018).

Figure 1.Ebolavirus. A) Scanning electron micrograph of Ebola virus particles (blue) budding from an infected grivet (Chlorocebus aethiops (Linnaeus, 1758)) Vero E6 cell. B) Transmission electron micrograph of Ebola virus particles (blue) found both as extracellular particles and budding particles from infected Vero E6 cells. Images are colorized for clarity. Courtesy of John G. Bernbaum and Jiro Wada, NIH/NIAID/DCR/IRF-Frederick, Fort Detrick, MD, USA.

Physicochemical and physical properties

EBOV particles have a molecular mass of about 3.82×105 kD. The buoyant density of EBOV particles in potassium tartrate is about 1.14 g/ml. The sedimentation coefficient (S20,w) of uniform filamentous particles is 1,300–1,400 S, but higher for longer particles. The nucleocapsid has a buoyant density in cesium chloride (CsCl) of about 1.32 g cm−3 (Kiley et al., 1980). 

Nucleic acid

Ebolavirus genomes are linear non-segmented RNA molecules of negative polarity. The genomes are about 18.9 kb. Genomic RNAs are not polyadenylated at their 3′-ends, and there is no evidence for 5′-end terminal cap structures or covalently linked proteins. The Mr of genomic RNA is about 4.2×106 and represents about 1.1% of the total virion mass (Kiley et al., 1980, Boehmann et al., 2005, Elliott et al., 1985, Regnery et al., 1980).


Ebolaviruses express seven structural proteins, all of which are homologous to those of cuevaviruses, dianloviruses, and marburgviruses (Table 1.Ebolavirus). The second most abundant structural protein in virions is the nucleoprotein (NP), which encapsidates the ebolavirus genome. The least abundant protein is the large protein (L), which mediates ebolavirus genome replication and transcription (Sanchez et al., 1993, Kiley et al., 1980). The ebolavirus RNP complex consists of NP, RNP complex‑associated protein (VP24), polymerase cofactor (VP35), transcriptional activator (VP30), and L. The RNP complexes associate with the matrix protein (VP40), which line the inner side of the virion membrane, and the glycoprotein (GP1,2), which forms globular spikes on the outside of the virion membrane (Beniac et al., 2012, Sugita et al., 2018, Kirchdoerfer et al., 2017, Mühlberger et al., 1999, Banadyga et al., 2017). Similar to cuevaviruses, but unlike dianloviruses and marburgviruses, ebolaviruses express their structural glycoprotein (GP1,2) via co‑transcriptional editing and also express three soluble glycoproteins from the GP gene (sGP, ssGP, and Δ-peptide) (Sanchez et al., 1996, Volchkov et al., 1995, Volchkova et al., 1999, Mehedi et al., 2011).

Table 1.Ebolavirus. Location and functions of ebolavirus structural proteins.

Protein (abbreviation)

Encoding gene




Nucleoprotein (NP)

1 (NP)

RNP complex component; second‑most abundant protein in infected cells and in virons; consists of two distinct functional modules; homo‑oligomerizes to form helical polymers; binds to genomic and antigenomic RNA, VP35, VP40, VP30, and VP24; phosphorylated, O‑glycosylated, and possibly sialylated, interacts with PP2A

Nucleocapsid and cellular inclusion body formation; encapsidation of ebolavirus genome and antigenome; genome replication and transcription

(Sugita et al., 2018, Mühlberger et al., 1999, Su et al., 2018, Watanabe et al., 2006, Peyrol et al., 2013, Groseth et al., 2009, Hoenen et al., 2012, Ebihara et al., 2006, Huang et al., 2002, Kirchdoerfer et al., 2015, Kruse et al., 2018)

Polymerase cofactor (VP35)

2 (VP35)

RNP complex component; homo‑oligomer; phosphorylated; binds to double‑stranded RNA, NP, VP30, and L

Replicase-transcriptase cofactor; inhibits innate immune response by interfering with IRF3, IRF7, IFIH1, DDX58, and RNAi pathways; inhibits stress granule formation

(Mühlberger et al., 1999, Kirchdoerfer et al., 2015, Basler et al., 2003, Basler et al., 2000, Cárdenas et al., 2006, Haasnoot et al., 2007, Kimberlin et al., 2010, Leung et al., 2010, Reid et al., 2005, Nelson et al., 2016, Biedenkopf et al., 2013)

Matrix protein (VP40)

3 (VP40)

Most abundant protein in infected cells and in virons; consists of two distinct functional modules; homo‑oligomerizes to form dimers and circular hexamers and octamers; SUMOylated; binds single‑stranded RNA, tubulin alpha, VP35; hydrophobic; membrane‑associated; contains three late‑budding motifs; binds to NEDD4 and TSG101; binds to tubulin alpha and is ubiquitinylated

Matrix component; regulation of genome transcription and replication; regulation of virion morphogenesis and egress

(Bornholdt et al., 2013, Harty et al., 2000, Licata et al., 2003, Noda et al., 2002, Baz-Martínez et al., 2016, Clifton et al., 2015, Dessen et al., 2000, Hoenen et al., 2010, Panchal et al., 2003, Pavadai et al., 2018, Timmins et al., 2003)

Secreted glycoprotein (sGP)

4 (GP)

Mostly nonstructural; secreted as a parallel homo‑dimer in high amounts from infected cells; N‑glycosylated, C‑mannosylated

Unknown. Hypothesized to be an antibody-decoy and an anti‑inflammatory agent

(Falzarano et al., 2007, Volchkova et al., 1998, Barrientos et al., 2004, Falzarano et al., 2006, de La Vega et al., 2015)

Glycoprotein (GP1,2)

4 (GP)

Type I transmembrane and class I fusion protein; cleaved to GP1 and GP2 subunits that heterodimerize; mature protein is a trimer of GP1,2 heterodimers; inserts into membranes; heavily N- and O‑glycosylated, sialylated, acylated, phosphorylated. ADAM17 converts GP1,2 into a soluble form (GP1,2Δ)

Virion adsorption to ebolavirus‑susceptible cells via cellular attachment factors; determines ebolavirus cell and tissue tropism; induction of virus‑cell membrane fusion subsequent to endolysosomal binding to NPC1; inhibits innate immune response by interfering with BST2. GP1,2Δ triggers immune activation and increased vascular permeability

(Ito et al., 2001, Carette et al., 2011, Côté et al., 2011, Chandran et al., 2005, Schornberg et al., 2006, Lee et al., 2008, Collar et al., 2017, Ritchie et al., 2010, Beniac and Booth 2017, Jeffers et al., 2002, Kaletsky et al., 2009, Malashkevich et al., 1999, Tran et al., 2014, Volchkov et al., 1998a, Volchkov et al., 1998b, Wang et al., 2016, Jouvenet et al., 2009, Dolnik et al., 2004, Takada et al., 1997, Escudero-Pérez et al., 2014)

Secondary secreted glycoprotein (ssGP)

4 (GP)

Predominantly nonstructural; secreted as a N‑glycosylated monomer


(Mehedi et al., 2011, Volchkova et al., 1998)


4 (GP)

Nonstructural; secreted; largely unstructured; O‑glycosylated and sialylated

Hypothesized to suppress filovirus superinfection and/or act as a viroporin

(Radoshitzky et al., 2011, Volchkova et al., 1999, He et al., 2017, Pokhrel et al., 2019)

Transcriptional activator (VP30)

5 (VP30)

RNP complex component; hexameric zinc finger protein; binds single-stranded RNA, NP, VP35 and L; phosphorylated; interacts with SRPK1 and SRPK2

Transcription initiation, reinitiaition, and antitermination; regulation of genome transcription and replication

(Mühlberger et al., 1999, Groseth et al., 2009, Biedenkopf et al., 2013, Biedenkopf et al., 2016a, Biedenkopf et al., 2016, John et al., 2007, Modrof et al., 2003, Modrof et al., 2002, Xu et al., 2017, Weik et al., 2002, Takamatsu et al., 2020)

RNP complex-associated protein (VP24)

6 (VP24)

RNP complex component; homo‑tetramerizes; hydrophobic and membrane‑associated

Regulation of genome transcription and replication; regulation of virion morphogenesis and egress; inhibits phosphorylation of MAPK and prevents karyopherin shuttling from cytoplasm into the nucleus; inhibits host cell signaling downstream of IFNA1/B1/G

(Banadyga et al., 2017, Ebihara et al., 2006, Halfmann et al., 2011, Han et al., 2003, Hoenen et al., 2006, Mateo et al., 2011, Reid et al., 2007, Schwarz et al., 2017, Watanabe et al., 2007, Xu et al., 2014, Zhang et al., 2012, Wan et al., 2017)

Large protein (L)

7 (L)

RNP complex component; homo‑dimerizes; binds to genomic and antigenomic RNA, VP35, and VP30; mRNA capping enzyme

Genome replication and mRNA transcription; co‑transcriptional editing

(Sanchez et al., 1996, Volchkov et al., 1995, Mühlberger et al., 1999, Groseth et al., 2009, Trunschke et al., 2013, Ferron et al., 2002, Tchesnokov et al., 2018, Shabman et al., 2013)

ADAM17, ADAM metallopeptidase domain 17; DDX58, DExD/H-box helicase 58; IFIH1, interferon induced with helicase C domain 1; IFNA1, interferon alpha 1; IFNB1, interferon beta 1; IFNG, interferon gamma; IRF, interferon regulatory factor; MAPK, mitogen-activated protein kinase; NPC1, NPC intracellular cholesterol transporter 1; NEDD4, E3 ubiquitin protein ligase; PP2A, protein phosphatase 2; RNP, ribonucleoprotein; SRPK, SRSF protein kinase; SUMO, small ubiquitin-like modifier; TSG101, tumor susceptibility 101; VP, virus protein 


The viral envelope is derived from host cell membranes and is considered to have a lipid composition similar to that of the host cell plasma membrane (Bavari et al., 2002, Feizpour et al., 2015). Ebolavirus glycoproteins are acylated (Ito et al., 2001). 


The glycoproteins of ebolaviruses are highly glycosylated with N-linked high mannose, hybrid, and bi-, tri-, and tetra‑antennary complex glycans with and without fucose and sialic acid and with O‑linked glycans of the neutral mucin type. Glycans constitute >50% of the GP1,2 total mass. In contrast to marburgvirus GP1,2, ebolavirus GP1,2, may be strongly sialylated (Collar et al., 2017, Ritchie et al., 2010). Ebolavirus NP is O-glycosylated and possibly sialylated (Watanabe et al., 2006, Huang et al., 2002). sGP is N-glycosylated and C-mannosylated (Falzarano et al., 2007, Falzarano et al., 2006). ssGP is N-glycosylated (Mehedi et al., 2011). Δ-peptide is O‑glycosylated and sialylated (Volchkova et al., 1999).

Genome organization and replication

The ebolavirus genome has the gene order 3′-NP-VP35-VP40-GP-VP30-VP24-L-5′ (Figure 2.Ebolavirus). The extragenic sequences at the extreme 3′-end (leader) and 5′-end (trailer) of the genome are conserved and partially complementary. Genes are flanked by conserved transcriptional initiation and termination (polyadenylation) sites. Most genes are separated by non‑conserved intergenic sequences, but some genes overlap. Most of these overlaps are extremely short and limited to a highly conserved pentamer. In addition, most genes possess relatively long 3′- and 5′-noncoding regions (Sanchez et al., 1993, Ikegami et al., 2001, Sanchez and Rollin 2005, Towner et al., 2008). Similar to cuevaviruses, but contrary to dianloviruses and marburgviruses, the GP genes of ebolaviruses possess three overlapping open reading frames (ORFs) that can be joined through co-transcriptional polymerase stuttering (Sanchez et al., 1996, Volchkov et al., 1995).

Figure 2.Ebolavirus. Schematic representation of the ebolavirus genome organization. Genomes are drawn to scale. Courtesy of Jiro Wada, IRF-Frederick, Fort Detrick, MD, USA.

The replication strategy of ebolaviruses is highly similar to that of cuevaviruses and reminiscent of that of dianloviruses and marburgviruses (Brauburger et al., 2015, Manhart et al., 2018). Ebolavirions enter host cells mainly by macropinocytosis (Aleksandrowicz et al., 2011, Nanbo et al., 2010, Saeed et al., 2010). Ebolavirus GP1,2 mediates cell surface attachment factor (e.g., C‑type lectins, integrins, hepatitis A virus cellular receptor 1 [HAVCR1]) binding and subsequent low-pH-dependent fusion into endosomes (Davey et al., 2017). Cathepsin L and/or B cleavage is required for GP1,2 binding to the endosomal receptor NPC intracellular cholesterol transporter 1 (NPC1), which is also used by cuevaviruses, dianloviruses, and marburgviruses (Carette et al., 2011, Côté et al., 2011, Ng et al., 2014, Chandran et al., 2005, Schornberg et al., 2006, Misasi et al., 2012). Uncoating is presumed to occur in a manner analogous to that of other mononegaviruses. Ebolavirus transcription and genome replication take place in the cytoplasm and, in general, follow the models for members of the families Paramyxoviridae and Pneumoviridae. Transcription starts at the conserved transcriptional initiation site, and polyadenylation occurs at a stretch of uridine residues within the transcriptional termination site. The 5′‑terminal non-coding sequences likely form hairpin-like structures in all (capped and polyadenylated) mRNAs. Replication involves the synthesis of full-length positive-sense genome copies (antigenomes) (Brauburger et al., 2015, Weik et al., 2002, Sanchez and Kiley 1987, Bray et al., 2000). During infection, massive amounts of nucleocapsids accumulate intracellularly and form intracytoplasmic inclusion bodies, which are the sites of ebolavirus transcription, replication, and nucleocapsid assembly (Hoenen et al., 2012). Mature nucleocapsids are transported based on actin polymerization for envelopment to the plasma membrane, where budding occurs in a VP40-mediated process (Bornholdt et al., 2013, Harty et al., 2000, Licata et al., 2003, Noda et al., 2002, Pavadai et al., 2018, Schudt et al., 2015, Takamatsu et al., 2018, Grikscheit et al., 2020) (Figure 3.Filoviridae).


Ebolaviruses appear to be endemic in Western Africa (BOMV, EBOV, TAFV), Middle Africa (BDBV, EBOV), Eastern Africa (BDBV, SUDV), and Eastern and South-eastern Asia (RESTV). BOMV infects little free-tailed bats (Chaerephon pumilus (Cretzschmar, 1826)) and Angolan free‑tailed bats (Mops condylurus A. Smith, 1933), but the natural hosts of most other ebolaviruses are unknown and spread of ebolaviruses is not associated with any vector. (Bats are suspected hosts for all ebolaviruses; RESTV also naturally infects domestic pigs [Sus scrofa domesticus Erxleben, 1777].) The route of initial human infection is unknown (Amman et al., 2017). The major route of human-to-human transmission of ebolaviruses requires direct contact with blood, bodily fluids, or injured skin. (Kuhn et al., 2020). In the laboratory, rodents (laboratory mice, domesticated guinea pigs, golden hamsters), nonhuman primates (common marmosets, crab-eating macaques, grivets, hamadryas baboons, rhesus monkeys), carnivores (domestic ferrets), and suids (domestic pigs) can be infected experimentally with various ebolaviruses, but lethal infection of rodents requires sequential adaptation (Kuhn et al., 2020, Siragam et al., 2018, St Claire et al., 2017, Marsh et al., 2011).


The antigenicity of ebolaviruses is primarily due to their glycoproteins. Numerous anti‑GP1,2 monoclonal antibodies have been described that are specific for a particular ebolavirus or cross‑reactive among ebolaviruses. Importantly, the ability of a monoclonal antibody to neutralize ebolavirus infection in vitro is not necessarily predictive of protective efficacy in vivo; conversely, antibodies that are non-neutralizing in vitro have shown to be protective in vivo. Ebolaviruses and other filoviruses have only limited antigenic relatedness, and individual ebolaviruses can be differentiated with certain antibodies (Lee et al., 2008, Bramble et al., 2018, Dias et al., 2011, Flyak et al., 2018, Saphire et al., 2018, West et al., 2018, Wec et al., 2017).

Derivation of names

Ebolavirus: from the Ebola (Legbala) River in Zaire/Democratic Republic of the Congo, where the first registered outbreak of Ebola virus disease occurred (Henry 2015).

Species demarcation criteria

PAirwise Sequence Comparison (PASC) using coding-complete ebolavirus genomes is the primary tool for ebolavirus species demarcation. Genomic sequences of ebolaviruses of different species differ from each other by ≥23% (Bào et al., 2017). Genomic features, such as number and location of gene overlaps, ebolavirus host and geographic distribution, and ebolavirus pathogenicity for different organisms are also taken into account for species assignment.

Phylogenetic relationships across the genus have been established from maximum‑likelihood trees generated using coding-complete or complete genome sequences (Figure 4.Filoviridae) or by phylogenetic analysis of RNA-directed RNA polymerase (RdRP) sequences (Wolf et al., 2018).

Member species

Exemplar isolate of the species
SpeciesVirus nameIsolateAccession numberRefSeq numberAvailable sequenceVirus Abbrev.
Bombali ebolavirusBombali virusBombali virus/M.condylurus-wt/SLE/2016/PREDICT_SLAB000156MF319185NC_039345Complete genomeBOMV
Bundibugyo ebolavirusBundibugyo virusBundibugyo virus/H.sapiens-tc/UGA/2007/Butalya-811250FJ217161NC_014373Complete genomeBDBV
Reston ebolavirusReston virusReston virus/M.fascicularis-tc/USA/1989/Philippines89-PennsylvaniaAF522874NC_004161Complete genomeRESTV
Sudan ebolavirusSudan virusSudan virus/H.sapiens-tc/UGA/2000/Gulu-808892AY729654NC_006432Complete genomeSUDV
Tai Forest ebolavirusTaï Forest virusTaï Forest virus/H.sapiens-tc/CIV/1994/Pauléoula-CIFJ217162NC_014372Complete coding genomeTAFV
Zaire ebolavirusEbola virusEbola virus/H.sapiens-tc/COD/1976/Yambuku-MayingaAF086833NC_002549Complete genomeEBOV

Virus names, the choice of exemplar isolates, and virus abbreviations, are not official ICTV designations.