Filoviridae

The family Filoviridae is the taxonomic home of several related viruses that form filamentous virions. Two members of the family that are commonly known are Ebola virus and Marburg virus. Both viruses, and some of their lesser known relatives, cause severe disease in humans and nonhuman primates in the form of viral hemorrhagic fevers.^[1] All accepted members of the family (all ebolaviruses and marburgviruses) are Select Agents,^[2] World Health Organization Risk Group 4 Pathogens (requiring Biosafety Level 4-equivalent containment),^[3] National Institutes of Health/National Institute of Allergy and Infectious Diseases Category A Priority Pathogens,^[4] Centers for Disease Control and Prevention Category A Bioterrorism Agents,^[5] and listed as Biological Agents for Export Control by the Australia Group.^[6] It is expected that "cuevaviruses", proposed to be additional members of the family,^[7] will be classified in a similar way in the near future.

Use of term

The family Filoviridae is a virological taxon (i.e. a man-made concept) that was created in 1982^[1] and emended in 1991,^[8] 1995,^[9] 2000,^[10] 2005,^[11] 2010^[7] and 2011.^[12] The family currently includes the three virus genera "Cuevavirus", Ebolavirus, and Marburgvirus and is included in the order Mononegavirales.^[7] The members of the family (i.e. the actual physical entities) are called filoviruses or filovirids.^[7] The name Filoviridae is derived from the Latin noun filum (alluding to the filamentous morphology of filovirions) and the taxonomic suffix -viridae (which denotes a virus family).^[1]

Note

Filoviridae is pronounced ˌfiːloʊ’viːrɨdɛ (IPA) or fee-loh-vee-ri-deh in English phonetic notation.^[7] According to the rules for taxon naming established by the International Committee on Taxonomy of Viruses (ICTV), the name Filoviridae is always to be capitalized, italicized, never abbreviated, and to be preceded by the word "family". The names of its members (filoviruses/filovirids) are to be written in lower case, are not italicized, and used without articles.^[7][12]

Family inclusion criteria

A virus that fulfills the criteria for being a member of the order Mononegavirales is a member of the family Filoviridae if^[7][12]

• it causes viral hemorrhagic fever in certain primates
• it infects primates, pigs or bats in nature
• it needs to be adapted through serial passage to cause disease in rodents
• it exclusively replicates in the cytoplasm of a host cell
• it has a genome ≈19 kb in length
• it has an RNA genome that constitutes ≈1.1% of the virion mass
• its genome has a molecular weight of ≈4.2 x 10⁶
• its genome contains one or more gene overlaps
• its genome contains seven genes in the order 3'-UTR-NP-VP35-VP40-GP-VP30-VP24-L-5'-UTR
• its VP24 gene is not homologous to genes of other mononegaviruses
• its genome contains transcription initiation and termination signals not found in genomes of other mononegaviruses
• it forms nucleocapsids with a buoyant density in CsCl of ≈1.32 g/cm³
• it forms nucleocapsids with a central axial channel (≈10-15 nm in width) surrounded by a dark layer (≈20 nm in width) and an outer helical layer (≈50 nm in width) with a cross striation (periodicity of ≈5 nm)
• it expresses a class I fusion glycoprotein that is highly N- and O-glycosylated and acylated at its cytoplasmic tail
• it expressess a primary matrix protein that is not glycosylated
• it forms virions that bud from the plasma membrane
• it forms virions that are predominantly filamentous (U- and 6-shaped) and that are ≈80 nm in width, and several hundred nm and up to 14 μm in length
• it forms virions that have surface projections ≈7 nm in length spaced ≈10 nm apart from each other
• it forms virions with a molecular mass of ≈3.82 x 10⁸; an S_20W of at least 1.40; and a buoyant density in potassium tartrate of ≈1.14 g/cm³
• it forms virions that are poorly neutralized in vivo

Family organization

Table legend: "*" denotes type species; "proposed" refers to taxa that have been formally proposed to the ICTV; all other taxa listed here are formally accepted by the ICTV.

Nomenclature below species level

Recommendations have been made for the identification of these viruses below the species level.^[13] These include the use of virus name / strain / isolation host-suffix / country of sampling / year of sampling / genetic variant designation / isolate designation. The use of the suffix "rec" is recommended if the virus has been identified via recombinant DNA.

Phylogenetics

The mutation rates in these genomes have been estimated to be between 0.46 × 10^-4 and 8.21 × 10^-4 nucleotide substitutions/site/year.^[14] The most recent common ancestor of both the Reston and Zaire species has been estimated to be ~1960. The most recent common ancestor of the Marburg and Sudan species appears to have evolved 700 and 850 years before present respectively. The complete family appears to have evolved ~10,000 years before the present.

Life cycle

The filovirus life cycle begins with virion attachment to specific cell-surface receptors, followed by fusion of the virion envelope with cellular membranes and the concomitant release of the virus nucleocapsid into the cytosol. The virus RdRp partially uncoats the nucleocapsid and transcribes the genes into positive-stranded mRNAs, which are then translated into structural and nonstructural proteins. Filovirus RdRps bind to a single promoter located at the 3' end of the genome. Transcription either terminates after a gene or continues to the next gene downstream. This means that genes close to the 3' end of the genome are transcribed in the greatest abundance, whereas those toward the 5' end are least likely to be transcribed. The gene order is therefore a simple but effective form of transcriptional regulation. The most abundant protein produced is the nucleoprotein, whose concentration in the cell determines when the RdRp switches from gene transcription to genome replication. Replication results in full-length, positive-stranded antigenomes that are in turn transcribed into negative-stranded virus progeny genome copies. Newly synthesized structural proteins and genomes self-assemble and accumulate near the inside of the cell membrane. Virions bud off from the cell, gaining their envelopes from the cellular membrane they bud from. The mature progeny particles then infect other cells to repeat the cycle.^[11]

Paleovirology

Filoviruses have a history that dates back several tens of million of years. Endogenous viral elements (EVEs) that appear to be derived from filovirus-like viruses have been identified in the genomes of bats, rodents, shrews, tenrecs, tarsiers, and marsupials.^[15][16][17] Although most filovirus-like EVEs appear to be pseudogenes, evolutionary analyses suggest that orthologs isolated from several species of the bat genus Myotis have been maintained by selection.^[18]

References

Further reading

External links

• International Committee on Taxonomy of Viruses (ICTV)