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Members of the family Filoviridae produce variously shaped, often filamentous, enveloped virions containing linear non-segmented, negative-sense RNA genomes of 15–19 kb. The family currently includes five 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.
Marburg virus [DQ217792], species Marburg marburgvirus, genus Marburgvirus
Enveloped, variously shaped, typically with a single nucleocapsid
Approximately 15–19 kb of linear, negative-sense, non-segmented RNA
Antigenomic RNA is a replication intermediate. Both the genome and the antigenome form ribonucleoprotein complexes, which serve as templates
From multiple 5′-capped and 3′-polyadenylated mRNAs
Primates (ebolaviruses, marburgviruses), bats (marburgviruses, likely also cuevaviruses, ebolaviruses), domestic pigs (Reston virus), and probably fish (striaviruses, thamnoviruses) become naturally infected
Phylum Negarnaviricota, subphylum Haploviricotina, class Monjiviricetes, order Mononegavirales. The family includes five genera (Cuevavirus, Ebolavirus, Marburgvirus, Striavirus, and Thamnovirus) and a total of nine species
Viruses assigned to each of the 5 genera form a monophyletic clade based on phylogenetic analysis of RNA-dependent RNA polymerase (L) sequences (Wolf et al., 2018). Genomes of viruses from all 5 genera have a similar genome architecture.
Genus Cuevavirus. This genus currently includes one species for one virus (Lloviu virus [LLOV]) discovered in dead miniopterid bats (likely incidental hosts). Cuevaviruses are notable for genomes expressing the ribonucleoprotein (RNP) complex-associated protein (VP24) and the RNA-dependent RNA polymerase (L) from a bicistronic mRNA rather than from individual transcripts (ebolaviruses, marburgviruses) (Negredo et al., 2011).
Genus Ebolavirus. This genus currently includes five species for five viruses. Two of these viruses, Ebola virus (EBOV) and Reston virus (RESTV) are suspected to be harbored by bats as natural hosts. RESTV has also been found in pigs. Three ebolaviruses (Bundibugyo virus [BDBV], EBOV, and Sudan virus [SUDV]) are highly lethal human pathogens. Taï Forest virus (TAFV) has caused a single case of severe but non-lethal human disease, whereas RESTV has, thus far, only caused inapparent human infections (Kuhn 2018). 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. The genus currently includes one species for two viruses found in pteropodid bats. Both viruses (Marburg virus [MARV] and Ravn virus [RAVV]) are highly lethal human pathogens (Kuhn 2018).
Genus Striavirus. This genus includes one species for one virus (Xīlǎng virus [XILV]) discovered in captured frogfish (family Antennariidae) (likely naturally infected host). Striaviruses are notable for genomes that do not encode surface glycoproteins (GP1,2) homologous to those encoded by cuevaviruses, ebolaviruses, and marburgviruses (Shi et al., 2018).
Genus Thamnovirus. This genus includes one species for one virus (Huángjiāo virus [HUJV]) discovered in captured filefish (family Monacanthidae) (likely naturally infected host). Thamnoviruses are notable for genomes that do not encode GP1,2, matrix protein (VP40), and transcriptional activator (VP30) proteins homologous to those encoded by cuevaviruses, ebolaviruses, and marburgviruses (Shi et al., 2018).
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, IRF-Frederick, Fort Detrick, MD, USA.
Physicochemical and physical properties have only been described for individual ebolaviruses and marburgviruses and are described in the respective genus pages.
Filovirus genomes are linear, non-segmented RNA molecules of negative polarity. The genomes vary from ≈15 kb (thamnoviruses) to ≈19 kb (cuevaviruses, ebolaviruses, marburgviruses) (Negredo et al., 2011, Shi et al., 2018, Sanchez et al., 1993, Feldmann et al., 1992).
Filoviruses express six to ten proteins. RNP complexes are composed of a genomic RNA molecule and several types of structural proteins, one of them being the RNA-dependent RNA polymerase (L) (Ortín and Martín-Benito 2015).
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).
Carbohydrate composition has only been described for individual ebolaviruses and marburgviruses and is described in the respective genus pages.
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, Sanchez et al., 1993, Feldmann et al., 1992). The extragenic sequences at the extreme 3′- (leader) and 5′- (trailer) ends 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 overlap. Most genes possess relatively long 3′- and 5′-noncoding regions (Brauburger et al., 2015, Kuhn 2008).
Figure 2.Filoviridae. Schematic representation of the filovirus genome organization. Genomes are drawn to scale. Courtesy of Jiro Wada, 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 Niemann-Pick disease, type C1 (NPC1, white zigzag) 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 semicircles]) transcribes filovirus mRNAs that 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 of progeny virions at the plasma membrane (Kolesnikova et al., 2017). Courtesy of Jiro Wada, IRF-Frederick, Fort Detrick, MD, USA.
Due to the absence of replicating cuevavirus, striavirus, and thamnovirus isolates, pan-filovirus antigenicity studies have not been done.
Filoviruses appear to be endemic in Western Africa (EBOV, MARV, TAFV), Middle Africa (BDBV, EBOV, MARV), Eastern Africa (BDBV, SUDV, MARV, RAVV), Southern Africa (MARV), Eastern Asia (HUJV, RESTV, XILV), South-eastern Asia (RESTV), and Eastern and Southern Europe (LLOV). Naturally infected hosts of filoviruses are bats (MARV, RAVV; likely also ebolaviruses; possibly also LLOV), likely actinopterygian fish (HUJV, XILV), and domestic pigs (RESTV) (Shi et al., 2018, Kemenesi et al., 2018, Amman et al., 2017).
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 ORFs and/or genes, filovirus host and geographic distribution, and filovirus pathogenicity for different organisms are also taken into account for genus assignment.
Filoviridae: derived from Latin filum, “thread,” referring to the morphology of filovirus particles.
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 analyzing filovirus L amino acid 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 Dr. Nicholas Di Paola, PhD, USAMRIID, Fort Detrick, MD, USA.
Filoviruses are closely related to paramyxoviruses (Mononegavirales: Paramyxoviridae), pneumoviruses (Mononegavirales: Pneumoviridae), and sunviruses (Mononegavirales: Sunviridae) (Wolf et al., 2018).
Table 2.Filoviridae. Unclassified filoviruses (additional unclassified filoviruses that are probable members of existing genera are listed under individual genus descriptions).
(Yang et al., 2017)
(He et al., 2015)
(Yang et al., 2017, Yang et al., 2019)
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