Taxonomic Structure of the Order
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Order |
Mononegavirales |
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Family |
Bornaviridae |
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Genus |
Bornavirus |
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Family |
Filoviridae |
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Genus |
“Marburg-like viruses” |
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Genus |
“Ebola-like viruses” |
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Family |
Paramyxoviridae |
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Subfamily |
Paramyxovirinae |
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Genus |
Morbillivirus |
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Genus |
Respirovirus |
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Genus |
Rubulavirus |
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Subfamily |
Pneumovirinae |
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Genus |
Pneumovirus |
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Genus |
Metapneumovirus |
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Genus |
Rhabdoviridae |
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Genus |
Vesiculovirus |
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Genus |
Lyssavirus |
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Genus |
Ephemerovirus |
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Genus |
Novirhabdovirus |
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Genus |
Cytorhabdovirus |
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Genus |
Nucleorhabdovirus |
The order comprises four families of enveloped viruses possessing linear non-segmented, negative sense, ssRNA genomes. The families Filoviridae, Paramyxoviridae and Rhabdoviridae have features in common, which taken together with the apparent absence of genetic recombination, suggest a phylogenetic relationship. The common features include the negative strandedness of the monopartite genome, a similar gene order (3-non-translated region - core protein genes - envelope protein genes - a polymerase gene - 5-non-translated region), helical nucleocapsids, initiation of transcription by a virion associated RNA-dependent RNA polymerase from a single 3-promoter. The genomes of these three members of the order exhibit complementarity of the 3- and 5-termini, and 93-99% of the genome is protein-encoding. The ribonucleoprotein cores, but not the deproteinised RNA, are infectious. Maturation is by budding, predominately from the plasma membrane, rarely from internal membranes (rabies virus), or the inner nuclear membrane (several plant viruses). The family Bornaviridae exhibits a unique pattern of mRNA processing and has been included in the order on the basis of the negative strandedness of the monopartite ssRNA genome, similarity in genetic organization (Fig. 1), complementarity of the non-coding 5- and 3-termini, and homology of the transcription start and stop signal consensus sequences. The bornaviruses are distinctive because replication and transcription occurs in the nucleus and the polymerase contains a putative nuclear localization signal. Regions of conserved amino acid sequence homology are present in the L (polymerase) proteins, with the highest homology in the putative catalytic domain. The closest relationship of the L protein of Borna disease virus appears to be with the L protein of Sonchus yellow net virus, a member of the genus Nucleorhabdovirus. With the exception of the bornaviruses and the plant viruses classified in the genus Nucleorhabdovirus, all other members of the Order Mononegavirales multiply in the cytoplasm.
The virions are large enveloped structures with a prominent fringe of peplomers, 5-10 nm long and spaced 7-10 nm apart, in all except the family Bornaviridae. The morphologies are variable, but in general distinguish the families: 90 nm diameter spherical particles with a 50 nm diameter electron-dense core and without peplomers in the family Bornaviridae; simple, branched, U-shaped, 6-shaped or circular filaments of uniform diameter (about 80 nm) extending up to 14,000 nm are characteristic of viruses classified in the family Filoviridae, although purified virions are bacilliform and of uniform length (e.g., 790 nm in the case of Marburg virus); filamentous, pleomorphic or spherical structures of variable diameter are characteristic of viruses belonging to the family Paramyxoviridae; and regular bullet-shaped or bacilliform particles are characteristic of the member viruses of the family Rhabdoviridae. The ribonucleoprotein core has a diameter of 13-20 nm, which in viruses belonging to the families Filoviridae and Rhabdoviridae is organized into a helical nucleocapsid of about 50 nm diameter.
Physicochemical and Physical Properties
Virion Mr is 300-1,000 106. S20W is 550-1,045S (plant rhabdoviruses have larger S20W values). Virion buoyant density in CsCl 1.18-1.22 g/cm3. Virus infectivity is rapidly inactivated by heat treatment at 56°C, or following UV- or X-irradiation, or exposure to lipid solvents.
Virions contain one molecule of linear, non-infectious, negative sense, ssRNA, 8.9-19 kb in size, Mr of 3-5 106 which comprises about 0.5-2.0% of the particle weight. The viral RNA lacks a capped 5-terminus, or a covalently associated protein. The 3-terminus of viral RNA lacks a poly(A) tract. The 5- and 3-terminal regions exhibit inverse complementarity, and there are conserved motives in the terminal regions of all four families. Full-length positive sense (anti-genomic) RNAs are found in infected cells. The genome comprises a linear sequence of genes, with limited overlaps in some viruses, and with short terminal non-coding regions. There are conserved motifs in the transcription start and end signals in all families. The intergenic regions range from two to several hundred nucleotides. Exceptionally, genetic information may be encoded in all three reading frames in the P genes of respiroviruses and morbilliviruses. Splicing of some mRNA and overlapping start/stop signals are characteristic of bornaviruses.
There are a limited number of proteins in relation to the large particle size. The 5-7 structural proteins comprise envelope glycoprotein(s), a matrix protein, a major RNA-binding protein, other nucleocapsid-associated protein(s), and a large molecular weight polymerase protein, plus in some viruses several non-structural proteins which may be phosphorylated. The matrix protein is non-glycosylated in all except the bornaviruses. The matrix protein of Borna disease virus is N-glycosylated and expressed on the surface of virions. Enzymatic activities associated with the virions may include transcriptase, polyadenylate transferase, mRNA transferase, and neuraminidase.
Virions are composed of about 15-25% lipids, their composition reflecting that of the host cell membrane where virions bud. Generally, phospholipids represent about 55-60%, and sterols and glycolipids about 35-40% of the total lipids. Glycoproteins may have a covalently associated fatty acid proximal to the lipid envelope.
Virions are composed of about 3% carbohydrate by weight. The carbohydrates are present as N- and O-linked glycan chains on surface proteins and on glycolipids. When made in mammalian cells the oligosaccharide chains are generally of the complex type, in insect cells they are of the non-complex types.
Genome Organisation and Replication
In the families Filoviridae, Paramyxoviridae and Rhabdoviridae, discrete mRNAs are transcribed by sequential interrupted synthesis. Transcription is polar with stepwise attenuation. Generally genes do not overlap. The site of multiplication is the cytoplasm, with the exception of viruses classified in the genus Nucleorhabdovirus. in the family Bornaviridae, the site of multiplication is the nucleus. Transcription of bornavirus genomes is complex with splicing of mRNA and overlapping stop/start signals. The P genes of respiroviruses and morbilliviruses are exceptional in that all three ORFs may be utilised via alternative non-AUG start codons, and mRNA editing occurs by insertion of non-templated nucleotides to change the reading frame for the expression of P gene products. Replication occurs by synthesis of a complete positive sense anti-genomic RNA. Genomic and anti-genomic RNAs are present as nucleocapsids. The mRNAs of bornaviruses are capped, but synthesis is not inhibited by alpha-amanitin suggesting that a cap-snatching mechansism is not involved. In the filoviruses, paramyxoviruses and rhabdoviruses maturation of the independently assembled helical nucleocapsid occurs by budding through host membranes with investment by a host-derived lipid envelope containing transmembrane proteins. The process of assembly and maturation of bornaviruses is not known at present.
Membrane glycoproteins are involved in antibody-mediated neutralisation. Virus serotypes are defined by the surface antigens. Filoviruses are an exception in that they are not neutralised in vitro. In bornaviruses, antibodies to both the glycosylated matrix protein, which may function as an attachment protein, and the gp94 envelope protein neutralise infectivity.
The host ranges vary from restricted to unrestricted. Filoviruses have only been isolated from primates. Paramyxoviruses occur only in vertebrates and no vectors are known. Rhabdoviruses infect invertebrates, vertebrates and plants. Some rhabdoviruses multiply in both invertebrates and vertebrates, some in invertebrates and plants, but none in all three. In human hosts the pathogenic potential tends to be characteristic of the family: i.e., haemorrhagic fever (Filoviridae); respiratory and neurological diseases (Paramyxoviridae); mild febrile to fatal neurological diseases (Rhabdoviridae). Bornaviruses have been isolated from horses, cattle, sheep, rabbits, rats, cats, ostriches, and man. The pathology associated with virus infection is variable. Infection of animals is associated with conditions ranging from behavioural disturbances to severe nonpurulent encephalomyelitis, and there is some evidence of association of bornavirus infection with neuropsychiatric illness in man. Cytopathology varies from none (bornaviruses and filoviruses) to rapidly lytic (rhabdoviruses and paramyxoviruses); syncytium formation is common in paramyxoviruses.
Phylogenetic Relationships within the Order
Phylogenetic relationships between the families Filoviridae, Paramyxoviridae and Rhabdoviridae are illustrated in Figure 2.
None reported.
Borna: from Borna, a town in Saxony.
Cyto: from Greek, kytos, “cell”.
Ebola: from the river Ebola, in Sudan and Zaire.
Ephemero: from Greek, ephemeros, “short-lived”.
Filo: from Latin, filo, “thread-like”.
Lyssa: from Greek, lyssa,“rage, fury, canine madness”.
Marburg: from the city of Marburg, in Germany.
Meta: from Greek, meta, “after”.
Mono: from Greek, monos, “single”.
Morbilli: from Latin morbillus, diminutive of morbus, “disease”.
Nega: from negative sense RNA.
Novi: sigla for the non (no-) virion (vi-) protein gene characterisitic of the genus.
Nucleo: from Latin Nux, nucis, “nut”.
Paramyxo: from Greek para, “by the side of”, and myxa, “mucus”.
Pneumo: from Greek, pneuma, “breath”.
Respiro: from Latin, respirare, “to breathe”.
Rhabdo: from Greek, rhabdos, “rod”.
Rubula: from Latin, ruber, “red”; Rubula inflans - old name for mumps.
Vesiculo: from Latin, vesicula, diminutive of vesica, “bladder, blister”.
Virales: from Latin virales, “viruses”.
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