Filoviridae
Ebolavirus structure and genome
Electron micrograph ofMarburg virus
Virus classification
(unranked):	Virus
Realm:	Riboviria
Kingdom:	Orthornavirae
Phylum:	Negarnaviricota
Class:	Monjiviricetes
Order:	Mononegavirales
Family:	Filoviridae
Genera
Cuevavirus Dianlovirus Ebolavirus Marburgvirus Striavirus Thamnovirus

Filoviridae (/ˌfaɪloʊˈvɪrɪdiː/^[1]) is afamily ofsingle-stranded negative-sense RNA viruses in theorderMononegavirales.^[2] Two members of the family that are commonly known areEbola virus andMarburg virus. Both viruses, and some of their lesser known relatives, cause severedisease inhumans and nonhumanprimates in the form ofviral hemorrhagic fevers.^[3]

All filoviruses are classified by the US asselect agents,^[4] by theWorld Health Organization as Risk Group 4 Pathogens (requiringBiosafety Level 4-equivalent containment),^[5] by theNational Institutes of Health/National Institute of Allergy and Infectious Diseases as Category A Priority Pathogens,^[6] and by theCenters for Disease Control and Prevention asCategory A Bioterrorism Agents,^[7] and are listed as Biological Agents for Export Control by theAustralia Group.^[8]

Use of term

ThefamilyFiloviridae is avirological taxon that was defined in 1982^[3] and emended in 1991,^[9] 1998,^[10] 2000,^[11] 2005,^[12] 2010^[13] and 2011.^[14] The family currently includes the sixvirusgeneraCuevavirus,Dianlovirus,Ebolavirus,Marburgvirus, Striavirus, andThamnovirus and is included in theorderMononegavirales.^[13] The members of the family (i.e. the actual physical entities) are called filoviruses or filovirids.^[13] The nameFiloviridae is derived from theLatinnounfilum (alluding to the filamentous morphology of filovirions) and thetaxonomicsuffix-viridae (which denotes a virus family).^[3]

Note

According to the rules for taxon naming established by theInternational Committee on Taxonomy of Viruses (ICTV), the nameFiloviridae is always to becapitalized,italicized, never abbreviated, and to be preceded by the word "family". The names of its members (filoviruses or filovirids) are to be written in lower case, are not italicized, and used withoutarticles.^[13][14]

Life cycle

The filoviruslife cycle begins with virion attachment to specific cell-surfacereceptors, followed byfusion of the virion envelope with cellular membranes and the concomitant release of the virusnucleocapsid into thecytosol. The viralRNA-dependent RNA polymerase (RdRp, or RNA replicase) partially uncoats the nucleocapsid andtranscribes thegenes into positive-strandedmRNAs, which are thentranslated into structural and nonstructuralproteins. Filovirus RdRps bind to a singlepromoter 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 thenucleoprotein, whoseconcentration 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 thecell membrane. Virionsbud 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.^[12]

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  Replication cycle of filoviruses and vectors

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  Replication cycle of filoviruses at and inside host cell

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  Schematic representation of the filovirus genome organization.

Family inclusion criteria

A virus that fulfills the criteria for being a member of the orderMononegavirales is a member of the familyFiloviridae if:^[13][14]

• it causesviral hemorrhagic fever in certainprimates
• it infectsprimates,pigs orbats innature
• it needs to beadapted throughserial passage to causedisease inrodents
• it exclusively replicates in thecytoplasm of ahostcell
• it has agenome ≈19kbp in length
• it has anRNA genome that constitutes ≈1.1% of the virion mass
• its genome has amolecular weight of ≈4.2×10⁶
• its genome contains one or moregene overlaps
• its genome contains seven genes in the order3'-UTR-NP-VP35-VP40-GP-VP30-VP24-L-5'-UTR
• itsVP24 gene is nothomologous to genes of othermononegaviruses
• its genome containstranscription initiation and termination signals not found in genomes of other mononegaviruses
• it forms nucleocapsids with abuoyant density inCsCl 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 fusionglycoprotein that is highlyN- andO-glycosylated andacylated at its cytoplasmic tail
• it expresses a primarymatrix protein that is not glycosylated
• it forms virions that bud from theplasma 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 amolecular mass of ≈3.82×10⁸; anS_20W of at least 1.40; and abuoyant density inpotassium tartrate of ≈1.14 g/cm³
• it forms virions that are poorlyneutralizedin vivo

Family organization

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.^[15] The most recent common ancestor of sequenced filovirus variants was estimated to be 1971 (1960–1976) for Ebola virus, 1970 (1948–1987) for Reston virus, and 1969 (1956–1976) for Sudan virus, with the most recent common ancestor among the four species included in the analysis (Ebola virus, Tai Forest virus, Sudan virus, and Reston virus) estimated at 1000–2100 years.^[16] The most recent common ancestor of the Marburg and Sudan species appears to have evolved 700 and 850 years before present respectively. Although mutational clocks placed the divergence time of extant filoviruses at ~10,000 years before the present, dating of orthologous endogenous elements (paleoviruses) in the genomes of hamsters and voles indicated that the extant genera of filovirids had a common ancestor at least as old as the Miocene (~16–23 million or so years ago).^[17]

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 ofbats,rodents,shrews,tenrecs,tarsiers, andmarsupials.^[18][19][20] Although most filovirus-like EVEs appear to bepseudogenes, evolutionary analyses suggest thatorthologs isolated from several species of the bat genusMyotis have been maintained by selection.^[21]

Vaccines

There are presently very limited vaccines for known filovirus.^[22] An effective vaccine against EBOV, developed in Canada,^[23] was approved for use in 2019 in the US and Europe.^[24][25] Similarly, efforts to develop a vaccine against Marburg virus are under way.^[26]

Mutation concerns and pandemic potential

There has been a pressing concern that a very slight genetic mutation to a filovirus such asEBOV could result in a change in transmission system from direct body fluid transmission to airborne transmission, as was seen in Reston virus (another member of genus Ebolavirus) between infected macaques. A similar change in the current circulating strains of EBOV could greatly increase the infection and disease rates caused by EBOV. However, there is no record of any Ebola strain ever having made this transition in humans.^[27]

TheDepartment of Homeland Security’s National Biodefense Analysis and Countermeasures Center considers the risk of a mutatedEbola virus strain with aerosol transmission capability emerging in the future as a serious threat to national security and has collaborated with theCenters for Disease Control and Prevention (CDC) to design methods to detect EBOV aerosols.^[28]

References

Further reading

External links

Wikispecies has information related toFiloviridae

• ICTV Report:FiloviridaeArchived 2023-03-20 at theWayback Machine
• "Filoviridae".NCBI Taxonomy Browser. 11266.Archived from the original on 2022-04-21. Retrieved2023-01-19.
• "FILOVIR". Scientific resources for research on filoviruses. Archived fromthe original on 2020-07-30. Retrieved2023-01-19.
• Theoretical Evidence That The Ebola Virus Zaire Strain May Be Selenium-Dependent: A Factor In Pathogenesis And Viral Outbreaks?Taylor 1995Archived 2020-12-01 at theWayback Machine
• Can Selenite Be An Ultimate Inhibitor Of Ebola And Other Viral Infections?Lipinski 2015Archived 2020-11-19 at theWayback Machine
• Many In West Africa May Be Immune To Ebola VirusNew York TimesArchived 2022-09-01 at theWayback Machine

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