Family: Filoviridae

Jens H. Kuhn​, Gaya K. Amarasinghe, Christopher F. Basler, Sina Bavari, Alexander Bukreyev​, Kartik Chandran, Ian Crozier​, Olga Dolnik, John M. Dye​, Pierre B. H. Formenty, Anthony Griffiths, Roger Hewson, Gary P. Kobinger​, Eric M. Leroy, Elke Mühlberger, Sergey V. Netesov (Нетёсов Сергей Викторович)​, Gustavo Palacios, Bernadett Pályi​, Janusz T. Pawęska, Sophie J. Smither, Ayato Takada (高田礼人)​, Jonathan S. Towner and Victoria Wahl

Corresponding author: Jens H. Kuhn (kuhnjens@mail.nih.gov)
Edited by: Stuart G. Siddell and Peter J. Walker
Posted: March 2019, updated October 2020
PDF: ICTV_Filoviridae.pdf

Summary 

Members of the family Filoviridae produce variously shaped, often filamentous, enveloped virions containing linear negative-sense non-segmented RNA genomes of 15–19 kb (Table 1. Filoviridae). The family includes six genera. Several filoviruses (e.g., Ebola virus, Marburg virus) are pathogenic for humans and highly virulent. Bats are natural hosts for some filoviruses (e.g., Marburg virus, Ravn virus), whereas others infect fish (e.g., Huángjiāo virus, Xīlǎng virus). 

Table 1. Filoviridae.  Characteristics of members of the family Filoviridae

Viruses assigned to the six genera form a monophyletic clade based on phylogenetic analysis of RNA-directed RNA polymerase (RdRP) sequences (Wolf et al., 2018). Genomes of viruses from all six genera have a similar genomic architecture. 

Mammalian Host

Genus Cuevavirus. This genus includes one species for one virus (Lloviu virus [LLOV]), discovered in dead miniopterid bats (likely incidental hosts). Cuevaviruses have only been reported from Europe. Cuevaviruses are notable for genomes expressing the ribonucleoprotein (RNP) complex-associated protein (VP24) and the large protein (L) from a bicistronic mRNA rather than from individual transcripts (dianloviruses, ebolaviruses, marburgviruses) (Negredo et al., 2011). 

Genus Dianlovirus. This genus includes one species for one virus (Měnglà virus [MLAV]), discovered in pteropodid bats. Dianloviruses have only been reported from China. The organization of dianlovirus genomes is highly reminiscent of marburgvirus genomes, but they contain four rather than only one gene overlap (Yang et al., 2019). 

Genus Ebolavirus. This genus includes six species for six viruses. One of these viruses, Bombali virus (BOMV), has been detected in molossid bats (Goldstein et al., 2018). Two additional viruses, Ebola virus (EBOV) and Reston virus (RESTV), are suspected to be harbored by bats as natural hosts. Five ebolaviruses (Bundibugyo virus [BDBV], EBOV, RESTV, Sudan virus [SUDV], and Taï Forest virus [TAFV]) are pathogenic for nonhuman primates. BDBV, EBOV, and SUDV are highly lethal human pathogens. Based on reports, TAFV has caused only a single case of severe but non-lethal human disease, and RESTV has, as far as is known, only caused one inapparent human infection. RESTV has also been found in domestic pigs. RESTV appears to be endemic in South-eastern Asia; all other ebolaviruses circulate in Africa (Kuhn et al., 2020). Ebolaviruses are notable for expressing 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). 

Genus Marburgvirus. This genus includes one species for two viruses found in pteropodid bats. Both viruses (Marburg virus [MARV] and Ravn virus [RAVV]) are highly lethal human pathogens that are endemic in Africa (Kuhn et al., 2020). 

Piscine Host

Genus Striavirus. This genus includes one species for one virus (Xīlǎng virus [XILV]), discovered in captured frogfish (family Antennariidae) from the East China Sea. Striaviruses are notable for genomes that contain nine gene overlaps, encode at least three proteins without obvious homologs in other filovirus genera, and do not encode VP24 (Shi et al., 2018, Hume and Mühlberger 2019).  

Genus Thamnovirus. This genus includes one species for one virus (Huángjiāo virus [HUJV]), discovered in captured filefish (family Monacanthidae) from the East China Sea. Thamnoviruses are notable for genomes that encode at least one protein without obvious homologs in other filovirus genera and do not encode matrix protein (VP40) or VP24 (Shi et al., 2018, Hume and Mühlberger 2019). 

Virion 

Morphology

Virion morphology (Figure 1. Filoviridae) has only been studied for ebolaviruses and marburgviruses and is described in the respective genus pages. 

Figure 1. Filoviridae.  A) Scanning electron micrograph of Marburg virus particles (red) budding from an infected grivet (Chlorocebus aethiops (Linnaeus, 1758)) Vero E6 cell. B) Transmission electron micrograph of Marburg virus particles (red) found both as extracellular particles and budding particles from 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

Physicochemical and physical properties have only been described for individual ebolaviruses and marburgviruses and are described in the respective genus pages. 

Nucleic acid

Filovirus genomes are linear non-segmented RNA molecules of negative polarity. The genomes vary from about 15 kb (thamnoviruses) to about 19 kb (cuevaviruses, ebolaviruses, and marburgviruses) (Negredo et al., 2011, Shi et al., 2018, Feldmann et al., 1992, Sanchez et al., 1993).  

Proteins

Filoviruses express 6 to 10 proteins. RNP complexes are composed of a genomic RNA molecule and several types of structural proteins, one of them being the large protein (L) (Ortín and Martín-Benito 2015). 

Lipids

The filovirion 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). Some filovirus proteins may be acylated (Funke et al., 1995, Ito et al., 2001).  

Carbohydrates

Carbohydrate composition has only been described for individual ebolaviruses and marburgviruses and is described in the respective genus pages. 

Genome organization and replication

Filovirus genomes are organized like most mononegavirus genomes, with the general gene order 3′‑N‑P‑M‑(G)‑L‑5′ (alternative terminology for filoviruses: 3′-NP-VP35-VP40-(GP)-L-5′), but differ in that they contain additional genes (Figure 2. Filoviridae) (Negredo et al., 2011, Shi et al., 2018, Feldmann et al., 1992, Sanchez et al., 1993). The extragenic sequences at the extreme 3′-end (leader) and 5′-end (trailer) of filovirus genomes are conserved, and short sections of these end sequences are complementary. Genes of non-fish filoviruses are flanked by conserved transcriptional initiation and termination (polyadenylation) sites typically containing the highly conserved pentamer 3′-UAAUU-5′. Genes may be separated by non-conserved intergenic sequences or overlaps. Most genes possess relatively long 3′- and 5′-noncoding regions (Kuhn et al., 2020, Hume and Mühlberger 2019, Brauburger et al., 2015). 

Figure 2. Filoviridae.  Schematic representation of the filovirus genome organization. Genomes are drawn to scale. Courtesy of Jiro Wada, NIH/NIAID/DCR/IRF-Frederick, Fort Detrick, MD, USA.

The replication strategies of filoviruses (Figure 3. Filoviridae) have only been studied in depth using EBOV and MARV and are discussed in the respective subchapters. 

Figure 3. Filoviridae.  Replication cycle of filoviruses (possibly excluding striaviruses and thamnoviruses). Virions attach to cell-surface attachment factors (orange Ys) and are taken into the cell via endocytosis (Davey et al., 2017). The filovirion glycoproteins (yellow clubs) bind to endosomal NPC intracellular cholesterol transporter 1 (NPC1, white zigzag) and catalyze the fusion of viral and cellular membranes to release the filovirus RNP complex (green helix) (Carette et al., 2011, Côté et al., 2011, Ng et al., 2014). The polymerase complex (consisting of VP35 [purple dots] and L [blue ovals]) transcribes filovirus mRNAs, which are translated into filovirus proteins, and replicates filovirus genomic RNA via antigenomic intermediates (Brauburger et al., 2015).  Genomic RNA and antigenomic RNA occur only as ribonucleoprotein complexes, which serve as templates for replication and/or transcription. Assembly of filoviral proteins and progeny genomes occurs in the cytoplasm and results in budding and release of virions at the plasma membrane (Kolesnikova et al., 2017). Courtesy of Jiro Wada, NIH/NIAID/DCR/IRF-Frederick, Fort Detrick, MD, USA.

Biology

Filoviruses appear to be endemic in Western Africa (BOMV, EBOV, MARV, TAFV), Middle Africa (BDBV, EBOV, MARV), Eastern Africa (BDBV, SUDV, MARV, RAVV), Southern Africa (MARV), Eastern Asia (HUJV, MLAV, RESTV, XILV), South-eastern Asia (RESTV), and Eastern and Southern Europe (LLOV). Naturally infected hosts of filoviruses are bats (BOMV, LLOV, MARV, RAVV, likely also ebolaviruses), likely actinopterygian fish (HUJV, XILV), and domestic pigs (RESTV) (Negredo et al., 2011, Yang et al., 2019, Goldstein et al., 2018, Shi et al., 2018, Amman et al., 2017, Kemenesi et al., 2018). 

Antigenicity 

Due to the absence of replicating cuevavirus, striavirus, and thamnovirus isolates, pan-filovirus antigenicity studies have not been done.  

Genus demarcation criteria 

PAirwise Sequence Comparison (PASC) using coding-complete filovirus genomes is the primary tool for filovirus genus demarcation. Genomic sequences of filoviruses of different genera differ from each other by ≥55% (Bào et al., 2017). Genomic features, such as number and location of gene overlaps, number of open reading frames (ORFs) and/or genes, filovirus host and geographic distribution, and filovirus pathogenicity for different organisms are also taken into account for genus assignment. 

Derivation of names 

Filoviridae: from Latin filum, “thread,” referring to the morphology of filovirus particles. 

Relationships within the family

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

Figure 4. Filoviridae. Phylogenetic relationships of filoviruses. Maximum-likelihood tree (midpoint-rooted) inferred by using coding-complete or complete filovirus genomes demonstrates the six distinct clades (genera) of the family. Sequences were aligned using Clustal-Omega version 1.2.1 (http://www.clustal.org/omega/) and were manually curated in Geneious version R9 (http://www.geneious.com). Trees were inferred in FastTree version 2.1 (Price et al., 2010) using a General Time Reversible (GTR) model with 20 Gamma‑rate categories, 5,000 bootstrap replicates, and exhaustive search parameters (-slow) and pseudocounts (-pseudo). Numbers near nodes on the trees indicate bootstrap values in decimal form. Tree branches are scaled to nucleotide substitutions per site. Tips of branches indicate GenBank accession numbers. Analysis courtesy of Nicholas Di Paola, USAMRIID, Fort Detrick, MD, USA. This phylogenetic tree and corresponding sequence alignment are available to download from the Resources page.

Relationships with other taxa

Filoviruses are closely related to paramyxoviruses (Mononegavirales: Paramyxoviridae), pneumoviruses (Mononegavirales: Pneumoviridae), and sunviruses (Mononegavirales: Sunviridae) (Wolf et al., 2018). 

Related, unclassified viruses 

Unclassified filoviruses (additional unclassified filoviruses that are probable members of existing genera are listed under individual genus descriptions). 

Virus names and virus abbreviations, are not official ICTV designations.