Filoviridae


The family Filoviridae, a member of the order Mononegavirales, is the taxonomic home of several related viruses that form filamentous infectious viral particles and encode their genome in the form of single-stranded negative-sense RNA. 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. All filoviruses are Select Agents, World Health Organization Risk Group 4 Pathogens, National Institutes of Health/National Institute of Allergy and Infectious Diseases Category A Priority Pathogens, Centers for Disease Control and Prevention Category A Bioterrorism Agents, and listed as Biological Agents for Export Control by the Australia Group.

Use of term

The family Filoviridae is a virological taxon that was defined in 1982 and emended in 1991, 1998, 2000, 2005, 2010 and 2011. The family currently includes the four virus genera Cuevavirus, Dianlovirus, Ebolavirus, and Marburgvirus and is included in the order Mononegavirales. The members of the family are called filoviruses or filovirids. The name Filoviridae is derived from the Latin noun filum and the taxonomic suffix -viridae.

Note

According to the rules for taxon naming established by the International Committee on Taxonomy of Viruses, the name Filoviridae is always to be capitalized, italicized, never abbreviated, and to be preceded by the word "family". The names of its members are to be written in lower case, are not italicized, and used without articles.

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:
Genus nameSpecies nameVirus name
CuevavirusLloviu cuevavirus*Lloviu virus
DianlovirusMěnglà virus
EbolavirusBombali ebolavirusBombali virus
EbolavirusBundibugyo ebolavirusBundibugyo virus
EbolavirusReston ebolavirusReston virus
EbolavirusSudan ebolavirusSudan virus
EbolavirusTaï Forest ebolavirusTaï Forest virus
EbolavirusZaire ebolavirus*Ebola virus
MarburgvirusMarburg marburgvirus*Marburg virus
MarburgvirusMarburg marburgvirus*Ravn virus

Table legend: "*" denotes type species.

Nomenclature below species level

Recommendations have been made for the identification of these viruses below the species level. 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. The most recent common ancestor of sequenced filovirus variants was estimated to be 1971 for Ebola virus, 1970 for Reston virus, and 1969 for Sudan virus, with the most recent common ancestor among the four species included in the analysis estimated at 1000–2100 years. 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 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.

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 viral RNA-dependent RNA polymerase 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.

Paleovirology

Filoviruses have a history that dates back several tens of million of years. Endogenous viral elements that appear to be derived from filovirus-like viruses have been identified in the genomes of bats, rodents, shrews, tenrecs, tarsiers, and marsupials. 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.

Vaccines and concerns

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