Filoviridae (/ˌfaɪloʊˈvɪrɪdiː/[1]) is a family of single-stranded negative-sense RNA viruses in the order Mononegavirales.[2] 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.[3]
All filoviruses are classified by the US as select agents,[4] by the World Health Organization as Risk Group 4 Pathogens (requiring Biosafety Level 4-equivalent containment),[5] by the National Institutes of Health/National Institute of Allergy and Infectious Diseases as Category A Priority Pathogens,[6] and by the Centers for Disease Control and Prevention as Category A Bioterrorism Agents,[7] and are listed as Biological Agents for Export Control by the Australia Group.[8]
Contents
1Use of term
1.1Note
2Life cycle
3Family inclusion criteria
4Family organization
5Phylogenetics
6Paleovirology
7Vaccines and concerns
8References
9Further reading
10External links
Use of term
The family Filoviridae is a virological 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 six virus genera Cuevavirus, Dianlovirus, Ebolavirus, Marburgvirus, Striavirus, and Thamnovirus and is included in the order Mononegavirales.[13] The members of the family (i.e. the actual physical entities) are called filoviruses or filovirids.[13] 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).[3]
Note
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 or filovirids) are to be written in lower case, are not italicized, and used without articles.[13][14]
Life cycle
Replication cycle of filoviruses and vectors
Replication cycle of filoviruses at and inside host cell
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 viral RNA-dependent RNA polymerase (RdRp, or RNA replicase) 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.[12]
Family inclusion criteria
Schematic representation of the filovirus genome organization.
A virus that fulfills the criteria for being a member of the order Mononegavirales is a member of the family Filoviridae if:[13][14]
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 kbp in length
it has an RNA genome that constitutes ≈1.1% of the virion mass
its genome has a molecular weight of ≈4.2×106
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 expresses 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 ≈3.82×108; an S20W 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
Family Filoviridae: genera, species, and viruses
Genus name
Species name
Virus name (abbreviation)
Cuevavirus
Lloviu cuevavirus
Lloviu virus (LLOV)
Dianlovirus
Mengla dianlovirus
Měnglà virus (MLAV)
Ebolavirus
Bombali ebolavirus
Bombali virus (BOMV)
Bundibugyo ebolavirus
Bundibugyo virus (BDBV; previously BEBOV)
Reston ebolavirus
Reston virus (RESTV; previously REBOV)
Sudan ebolavirus
Sudan virus (SUDV; previously SEBOV)
Taï Forest ebolavirus
Taï Forest virus (TAFV; previously CIEBOV)
Zaire ebolavirus
Ebola virus (EBOV; previously ZEBOV)
Marburgvirus
Marburg marburgvirus
Marburg virus (MARV)
Ravn virus (RAVV)
Striavirus
Xilang striavirus
Xīlǎng virus (XILV)
Thamnovirus
Huangjiao thamnovirus
Huángjiāo virus (HUJV)
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 of bats, rodents, shrews, tenrecs, tarsiers, and marsupials.[18][19][20] 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.[21]
Vaccines and concerns
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] There has been a pressing concern that a very slight genetic mutation to a filovirus such as EBOV 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]
References
^"Filoviridae". Merriam-Webster Dictionary. Retrieved July 28, 2018.
^ abcKiley MP, Bowen ET, Eddy GA, Isaäcson M, Johnson KM, McCormick JB, Murphy FA, Pattyn SR, Peters D, Prozesky OW, Regnery RL, Simpson DI, Slenczka W, Sureau P, van der Groen G, Webb PA, Wulff H (1982). "Filoviridae: A taxonomic home for Marburg and Ebola viruses?". Intervirology. 18 (1–2): 24–32. doi:10.1159/000149300. PMID 7118520.
^US Animal and Plant Health Inspection Service (APHIS) and US Centers for Disease Control and Prevention (CDC). "National Select Agent Registry (NSAR)". Retrieved 2011-10-16.
^US Department of Health and Human Services. "Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition". Retrieved 2011-10-16.
^US National Institutes of Health (NIH), US National Institute of Allergy and Infectious Diseases (NIAID). "Biodefense — NIAID Category A, B, and C Priority Pathogens". Archived from the original on 2011-10-22. Retrieved 2011-10-16.
^US Centers for Disease Control and Prevention (CDC). "Bioterrorism Agents/Diseases". Archived from the original on July 22, 2014. Retrieved 2011-10-16.
^The Australia Group. "List of Biological Agents for Export Control". Archived from the original on 2011-08-06. Retrieved 2011-10-16.
^McCormick, J. B. (1991). "Family Filoviridae". In Francki, R. I. B.; Fauquet, C. M.; Knudson, D. L.; et al. (eds.). Classification and Nomenclature of Viruses-Fifth Report of the International Committee on Taxonomy of Viruses. Archives of Virology Supplement. 2. Vienna, Austria: Springer. pp. 247–49. ISBN 0-387-82286-0.
^Jahrling, P. B.; Kiley, M. P.; Klenk, H.-D.; Peters, C. J.; Sanchez, A.; Swanepoel, R. (1995). "Family Filoviridae". In Murphy, F. A.; Fauquet, C. M.; Bishop, D. H. L.; Ghabrial, S. A.; Jarvis, A. W.; Martelli, G. P.; Mayo, M. A.; Summers, M. D. (eds.). Virus Taxonomy—Sixth Report of the International Committee on Taxonomy of Viruses. Archives of Virology Supplement. 10. Vienna, Austria: Springer. pp. 289–92. ISBN 3-211-82594-0.
^Netesov, S.V.; Feldmann, H.; Jahrling, P. B.; Klenk, H. D.; Sanchez, A. (2000). "Family Filoviridae". In van Regenmortel, M. H. V.; Fauquet, C. M.; Bishop, D. H. L.; Carstens, E. B.; Estes, M. K.; Lemon, S. M.; Maniloff, J.; Mayo, M. A.; McGeoch, D. J.; Pringle, C. R.; Wickner, R. B. (eds.). Virus Taxonomy—Seventh Report of the International Committee on Taxonomy of Viruses. San Diego, USA: Academic Press. pp. 539–48. ISBN 0-12-370200-3.
^ abFeldmann, H.; Geisbert, T. W.; Jahrling, P. B.; Klenk, H.-D.; Netesov, S. V.; Peters, C. J.; Sanchez, A.; Swanepoel, R.; Volchkov, V. E. (2005). "Family Filoviridae". In Fauquet, C. M.; Mayo, M. A.; Maniloff, J.; Desselberger, U.; Ball, L. A. (eds.). Virus Taxonomy—Eighth Report of the International Committee on Taxonomy of Viruses. San Diego, USA: Elsevier/Academic Press. pp. 645–653. ISBN 0-12-370200-3.
^ abcdeKuhn JH, Becker S, Ebihara H, Geisbert TW, Johnson KM, Kawaoka Y, Lipkin WI, Negredo AI, Netesov SV, Nichol ST, Palacios G, Peters CJ, Tenorio A, Volchkov VE, Jahrling PB (2010). "Proposal for a revised taxonomy of the family Filoviridae: Classification, names of taxa and viruses, and virus abbreviations". Archives of Virology. 155 (12): 2083–2103. doi:10.1007/s00705-010-0814-x. PMC 3074192. PMID 21046175.
^ abcKuhn, J. H.; Becker, S.; Ebihara, H.; Geisbert, T. W.; Jahrling, P. B.; Kawaoka, Y.; Netesov, S. V.; Nichol, S. T.; Peters, C. J.; Volchkov, V. E.; Ksiazek, T. G. (2011). "Family Filoviridae". In King, Andrew M. Q.; Adams, Michael J.; Carstens, Eric B.; et al. (eds.). Virus Taxonomy—Ninth Report of the International Committee on Taxonomy of Viruses. London, UK: Elsevier/Academic Press. pp. 665–671. ISBN 978-0-12-384684-6.
^Carroll SA, Towner JS, Sealy TK, McMullan LK, Khristova ML, Burt FJ, Swanepoel R, Rollin PE, Nichol ST (March 2013). "Molecular evolution of viruses of the family Filoviridae based on 97 whole-genome sequences". J. Virol. 87 (5): 2608–16. doi:10.1128/JVI.03118-12. PMC 3571414. PMID 23255795.
^Taylor, D. J.; Ballinger, M. J.; Zhan, J. J.; Hanzly, L. E.; Bruenn, J. A. (2014). "Evidence that ebolaviruses and cuevaviruses have been diverging from marburgviruses since the Miocene". PeerJ. 2: e556. doi:10.7717/peerj.556. PMC 4157239. PMID 25237605.
^Taylor DJ, Leach RW, Bruenn J (2010). "Filoviruses are ancient and integrated into mammalian genomes". BMC Evolutionary Biology. 10: 193. doi:10.1186/1471-2148-10-193. PMC 2906475. PMID 20569424.
^Belyi VA, Levine AJ, Skalka AM (2010). Buchmeier (ed.). "Unexpected Inheritance: Multiple Integrations of Ancient Bornavirus and Ebolavirus/Marburgvirus Sequences in Vertebrate Genomes". PLOS Pathogens. 6 (7): e1001030. doi:10.1371/journal.ppat.1001030. PMC 2912400. PMID 20686665.
^Katzourakis A, Gifford RJ (2010). "Endogenous Viral Elements in Animal Genomes". PLOS Genetics. 6 (11): e1001191. doi:10.1371/journal.pgen.1001191. PMC 2987831. PMID 21124940.
^Taylor DJ, Dittmar K, Ballinger MJ, Bruenn JA (2011). "Evolutionary maintenance of filovirus-like genes in bat genomes". BMC Evolutionary Biology. 11 (336): 336. doi:10.1186/1471-2148-11-336. PMC 3229293. PMID 22093762.
^Peters CJ, LeDuc JW (February 1999). "An Introduction to Ebola: The Virus and the Disease". The Journal of Infectious Diseases. 179 (Supplement 1): ix–xvi. doi:10.1086/514322. JSTOR 30117592. PMID 9988154.
^Plummer, Francis A.; Jones, Steven M. (2017-10-30). "The story of Canada's Ebola vaccine". CMAJ : Canadian Medical Association Journal. 189 (43): E1326–E1327. doi:10.1503/cmaj.170704. ISSN 0820-3946. PMC 5662448. PMID 29084758.
^Research, Center for Biologics Evaluation and (2020-01-27). "ERVEBO". FDA.
^CZARSKA-THORLEY, Dagmara (2019-10-16). "Ervebo". European Medicines Agency. Retrieved 2020-05-03.
^Keshwara, Rohan; Hagen, Katie R.; Abreu-Mota, Tiago; Papaneri, Amy B.; Liu, David; Wirblich, Christoph; Johnson, Reed F.; Schnell, Matthias J. (2019-03-05). "A Recombinant Rabies Virus Expressing the Marburg Virus Glycoprotein Is Dependent upon Antibody-Mediated Cellular Cytotoxicity for Protection against Marburg Virus Disease in a Murine Model". Journal of Virology. 93 (6). doi:10.1128/JVI.01865-18. ISSN 0022-538X. PMC 6401435. PMID 30567978.
^Kelland, Kate (19 September 2014). "Scientists see risk of mutant airborne Ebola as remote". Reuters. Retrieved 10 October 2014.
Further reading
Klenk, Hans-Dieter (1999). Marburg and Ebola Viruses. Current Topics in Microbiology and Immunology. 235. Berlin, Germany: Springer-Verlag. ISBN 978-3-540-64729-4.
Klenk, Hans-Dieter; Feldmann, Heinz (2004). Ebola and Marburg Viruses—Molecular and Cellular Biology. Wymondham, Norfolk, UK: Horizon Bioscience. ISBN 978-0-9545232-3-7.
Kuhn, Jens H. (2008). Filoviruses—A Compendium of 40 Years of Epidemiological, Clinical, and Laboratory Studies. Archives of Virology Supplement. 20. Vienna, Austria: Springer. ISBN 978-3-211-20670-6.
Ryabchikova, Elena I.; Price, Barbara B. (2004). Ebola and Marburg Viruses—A View of Infection Using Electron Microscopy. Columbus, Ohio, USA: Battelle Press. ISBN 978-1-57477-131-2.
External links
Wikimedia Commons has media related to Filoviridae.
Wikispecies has information related to Filoviridae.
ICTV Report:Filoviridae
"Filoviridae". NCBI Taxonomy Browser. 11266.
"FILOVIR". Scientific resources for research on filoviruses.
Theoretical Evidence That The Ebola Virus Zaire Strain May Be Selenium-Dependent: A Factor In Pathogenesis And Viral Outbreaks?Taylor 1995
Can Selenite Be An Ultimate Inhibitor Of Ebola And Other Viral Infections?Lipinski 2015
Many In West Africa May Be Immune To Ebola VirusNew York Times
v
t
e
Filoviridae
Ebolavirus
Outbreaks
1976 Sudan outbreak
1976 Zaire outbreak
2013−2016 West African Ebola virus epidemic
Timeline
Reported cases and deaths
Responses
United Nations Ebola Response Fund
Operation United Assistance
in Guinea
in Liberia
in Mali
in Nigeria
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in Spain
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Ouse to Ouse Tock
Womey massacre
Recent DR Congo outbreaks and epidemics
2014
2017
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Kivu epidemic
2020 Équateur
2021 North Kivu
Species
Bundibugyo ebolavirus
BDBV
Reston ebolavirus
RESTV
Sudan ebolavirus
SUDV
Taï Forest ebolavirus
TAFV
Zaire ebolavirus
EBOV
Drug candidates
BCX4430
Brincidofovir
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Favipiravir
FGI-103
FGI-104
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Notable people
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Salome Karwah
Sheik Umar Khan
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Popular culture
The Hot Zone(1995 book by Richard Preston)
Outbreak(1995 film)
Ebola Syndrome(1996 film)
Executive Orders(1996 novel)
93 Days(2016 film)
The Hot Zone(2019 miniseries based on Preston book)
Viruses.Viruses.2016 Mar 30;8(4). pii: E87. doi: 10.3390/v8040087.
Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine ca
Journal of virology.J Virol.2016 Mar 28;90(8):3890-901. doi: 10.1128/JVI.00101-16. Print 2016 Apr 15.
Recent experiments suggest that some glycoprotein (GP)-specific monoclonal antibodies (MAbs) can protect experimental animals against the filovirus Ebola virus (EBOV). There is a need for isolation of MAbs capable of neutralizing multiple filoviruses. Antibody neutralization assays for filoviruses f
filovirus / ˈfɪl əˈvaɪ rəs, ˈfaɪ lə‐ / Show Spelled [fil-uh-vahy-r uh s, fahy-l uh ‐] Show IPA noun, plural filoviruses. any of several filamentous, single-stranded RNA viruses of the family Filoviridae, defined by their unique appearance and ...