Eilat virus

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Eilat virus
Anopheles-female.JPG
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Kitrinoviricota
Class: Alsuviricetes
Order: Martellivirales
Family: Togaviridae
Genus: Alphavirus
Species:
Eilat virus

Eilat virus (EILV) is a unique Alphavirus which is known mainly for its host range restriction generally to insects (primarily to mosquitoes) by means of RNA replication. [1] The virus is found in the Negev desert. It is incapable of infecting vertebrate cells, differentiating it from other alphaviruses.

Contents

Virology

The structural form of an alphavirus. Alphavirus.png
The structural form of an alphavirus.

The Eilat virus is from the family Togaviridae , genus Alphavirus. Alphaviruses are miniature spherical shaped (around 70 nm in diameter) enveloped viruses that consist of a positive sense (5' to 3') RNA genome, which encompasses two ORF's (Open Reading Frame which is an incessant stretch of codons that do not contain a stop codon). [2] Four nonstructural proteins are encoded on two-thirds of the genome (5' end), which include nsP1, nsP2, nsP3, nsP4. While five structural proteins ( sPs; Capsid, E1, E2, E3, and 6K) are encoded on the one third part of the genome ( 3' portion).

By receptor-mediated endocytosis alphaviruses gain entry into a host cell. After acquiring access, the low endocytic pH allows for a conformational change that discloses an E1 fusion peptide. Thus, inducing the release of the nucleocapsid into the cytoplasm of the host cell. The nucleocapsids in turn aid in initiating virion budding from the host cell membrane.

Discovery

The Eilat virus was isolated during an arbovirus survey in the Negev desert between the years 1982 and 1984. However, it was initially obtained by Joseph Peleg from a pool of Anopheles coustani mosquitoes (from the isolates back in 1982). This specific isolation was performed in a study for over ninety-one identified viruses, and the EILV virus was found and isolated from the gut of the collected mosquitoes.

EILV location

The Negev Desert is sparse in flora and fauna, but it is the "natural" home of the Eilat virus. Israel-2013-Aerial 00-Negev-Makhtesh Ramon.jpg
The Negev Desert is sparse in flora and fauna, but it is the "natural" home of the Eilat virus.

The Eilat virus is located primarily in Africa and parts of the Middle East. It is found in regions where its natural vector (the Anopheles coustani) is situated. The place of its study however, plays an important role in the evolutionary significance of the EILV. The Negrev desert (being almost 13,000 km2) is considered the natural area of the virus. The area's average climate ranges from the lowest being -5 °C to the highest of around 46 °C (yearly). The EILV was named after the city of Eilat which is located in the south area of the Negev desert (close to the region where the pool of Anopheles coustani's are located).

Evolutionary importance

The Eilat virus shows an evolutionary change which may have occurred to alphaviruses. Normally, an alphavirus similar to that of the EILV would use mosquitoes as the vector of transmission to other (usually vertebrates) creatures. However, the Eilat virus can replicate consummately in an insect host and fails completely to even enter the cells of vertebrates. Based on experimental evidence when a relativity similar virus (SINV) was injected into vertebrate cell lines, the cells showed to have a great cytopathic effect. While when the same test was done on the EILV, the virus showed no cytopathic effect on the vertebrate cell lines. [1] Therefore, evolutionary these results aid in suggesting that EILV lost its capability in infecting vertebrate cells. Thus, EILV appears to be mosquito-specific and represents a previously undescribed complex within the genus Alphavirus. Reverse genetic studies of EILV may help in the discovery of determinants of alphavirus host range which balances disease emergence.

Areas of infection

When tested on four different mosquito species the Eilat virus had similar effects on certain organs of the mosquitos and did not infect other organs. [3] This bar graph shows the percentage of the specified mosquito species infected by the EILV in several different organs of the host.

10
20
30
40
50
60
70
80
90
100
Aedes aegypti
Aedes albopictus
Anopheles gambiae
Culex quinquefasciatus
  •   Anterior mid-gut
  •   Posterior mid-gut
  •   Hindgut
  •   Salivary Glands
  •   Ovaries
  •   Malpighian Tubules

Transmission

The virus's main hosts are mosquitoes, however it does have the ability to infect other insect cells. The Eilat virus's incapability of entering vertebrate cells was proven by infection with the EILV-expressing red fluorescent protein which was obtained from a second genomic promoter. The red fluorescent protein was promptly observed in mosquito cells and unseen in vertebrate cells. [2]

Oral transmission

The Eilat virus is unable to infect its host in low doses orally. When a few species of mosquito were fed (a blood meal) containing the Eilat virus in high doses, all test species did in fact get infected; however, when the dose range was lowered, the species would fail to get infected.

Venereal transmission

This virus (EILV) is typically transmitted sexually from one organism to another. This allows or aids the Eilat virus to naturally keep its complex in circulation. However, researchers are still contemplating the fact that the virus was found to be unable to infect the ovaries, which would normally be a subsequent event following sexual transmittance in other alphaviruses.

Chikungunya virus particles. Chikungunya virus particles-PHIL-17369.jpg
Chikungunya virus particles.

Though the EILV is host specific (insect only), it is highly related to a series of viruses which have a more expansive host range. This relation assists in diagnostic testing with the vertebrate infecting viruses. Researchers discovered that the structural proteins of the EILV can be replaced by those of (pathogenic to mammals) related viruses (by super infection exclusion/ Homologous interference). [4] This in turn will allow the virus to form a virus, (of broader host ranges), look alike to the immune system. Therefore, helping the immune system recognize these harmful viruses. [5] Researchers at the University of Texas Medical Branch used this concept for the Chikungunya virus by creating the UTMB test. This test aids in clinical diagnoses and is an affordable alternative to the use of inactivated viruses in diagnostic testing. [6]

VirusesAbbreviationSimilarities to EILV
Whataroa virusWHATV
  • Similarity in lengths of UTR's (untranslated regions on mRNA) and intergenic regions.
  • Nucleotide and amino acid sequence similarity ( 57%)
  • Completely identical E1 fusion peptide
  • High similarity to nonstructural and structural protein cleavage sites
Sindbis virus SINV
  • Similarity in lengths of UTR's and intergenic regions
  • Nucleotide and amino acid sequence similarity (56%)
  • Significant similarity to E1 fusion peptide
  • High similarity to nonstructural and structural protein cleavage sites
  • High similarity to ribosomal binding sites sequences
Trocara virusTROV
  • Similarity in lengths of UTR's and intergenic regions
  • Nucleotide and amino acid sequence similarity (53%)
  • High similarity to nonstructural and structural protein cleavage sites
Aura virusAURAV
  • Similarity in lengths of UTR's and intergenic regions
  • Nucleotide and amino acid sequence similarity (55%)
  • High similarity to ribosomal binding site sequences
  • High similarity to nonstructural and structural protein cleavage sites
Western equine encephalitis virus WEEV
  • Similarity in lengths of UTR's and intergenic regions
  • Nucleotide and amino acid sequence similarity (52%)
  • Significant similarity to E1 fusion peptide
Eastern equine encephalitis virus EEEV
  • Similarity in lengths of UTR's and intergenic regions
  • Nucleotide and amino acid sequence similarities (51%)
  • Significant similarity to E1 fusion peptide
Salmon pancreas disease virusSPDV
  • Similarity in lengths of UTR's and intergenic regions
  • Nucleotide and amino acid sequence similarities (43%)
Venezuelan equine encephalitis virus VEEV
  • Similarity in lengths of UTR's and intergenic regions
  • Nucleotide and amino acid sequence similarities (51%)
  • Significant similarity to E1 fusion peptide
Chikungunya virus CHIKV
  • Similarity in lengths of UTR's and intergenic regions
  • Nucleotide and amino acid sequence similarities (52%)
  • Significant similarity to E1 fusion peptide

Anopheles coustani's aid in natural maintenance

Anopheles are the prime natural vectors for the Eilat virus. They are also secondary vectors for the malaria virus. Anopheles-male.jpg
Anopheles are the prime natural vectors for the Eilat virus. They are also secondary vectors for the malaria virus.

The Eilat virus was first isolated from the specified species Anopheles coustani (mosquito species) located at the Negev desert. Though this virus was identified and labeled in the late 1980s, research began on it starting in the early 2000s. Since this mosquito species was the prime victim of the EILV it is thought to be the top factor in naturally maintaining the virus. Anopheles coustani may in fact be the only mosquito species which is a natural conservative for the EILV. This would make the EILV be the second alphavirus which is able to employ an Anopheles species as a natural vector. This mosquito species is also a secondary vector for the malaria virus and is located in regions of the Middle East and Africa.

Significance

The EILV (the Eilat virus) has a limited and restricted host range. It being the only alphavirus (mosquito-borne) which is unable to infect mammalian and other vertebrate cells indicates a quick evolutionary change that was done by an Alphavirus . The EILV is not just restricted to the genomic RNA replication level but it also is unable to gain entry into vertebrate cells. Therefore, with further study the Eilat virus can compensate in making clear the viral factors other pathogenic similar viruses have in obtaining a broader host range. Also, it makes a possible candidate in promoting vaccine development for other alphaviruses with the ability to infect vertebrate cells. However, since research on the Eilat virus has only recently been put into action, there is still much more to be gained (evolutionary, medically, and scientifically) from this unique mosquito-borne alphavirus.

Anopheles gambiae was only able to get infected by the EILV in the posterior mid-gut. Anopheles gambiae mosquito feeding 1354.p lores.jpg
Anopheles gambiae was only able to get infected by the EILV in the posterior mid-gut.

Related Research Articles

<i>Flaviviridae</i> Family of viruses

Flaviviridae is a family of enveloped positive-strand RNA viruses which mainly infect mammals and birds. They are primarily spread through arthropod vectors. The family gets its name from the yellow fever virus; flavus is Latin for "yellow", and yellow fever in turn was named because of its propensity to cause jaundice in victims. There are 89 species in the family divided among four genera. Diseases associated with the group include: hepatitis (hepaciviruses), hemorrhagic syndromes, fatal mucosal disease (pestiviruses), hemorrhagic fever, encephalitis, and the birth defect microcephaly (flaviviruses).

<i>Plasmodium</i> Genus of parasitic protists that can cause malaria

Plasmodium is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of Plasmodium species involve development in a blood-feeding insect host which then injects parasites into a vertebrate host during a blood meal. Parasites grow within a vertebrate body tissue before entering the bloodstream to infect red blood cells. The ensuing destruction of host red blood cells can result in malaria. During this infection, some parasites are picked up by a blood-feeding insect, continuing the life cycle.

<i>Flavivirus</i> Genus of viruses

Flavivirus, renamed Orthoflavivirus in 2023, is a genus of positive-strand RNA viruses in the family Flaviviridae. The genus includes the West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, Zika virus and several other viruses which may cause encephalitis, as well as insect-specific flaviviruses (ISFs) such as cell fusing agent virus (CFAV), Palm Creek virus (PCV), and Parramatta River virus (PaRV). While dual-host flaviviruses can infect vertebrates as well as arthropods, insect-specific flaviviruses are restricted to their competent arthropods. The means by which flaviviruses establish persistent infection in their competent vectors and cause disease in humans depends upon several virus-host interactions, including the intricate interplay between flavivirus-encoded immune antagonists and the host antiviral innate immune effector molecules.

<i>Bunyavirales</i> Order of RNA viruses

Bunyavirales is an order of segmented negative-strand RNA viruses with mainly tripartite genomes. Member viruses infect arthropods, plants, protozoans, and vertebrates. It is the only order in the class Ellioviricetes. The name Bunyavirales derives from Bunyamwera, where the original type species Bunyamwera orthobunyavirus was first discovered. Ellioviricetes is named in honor of late virologist Richard M. Elliott for his early work on bunyaviruses.

<i>Brome mosaic virus</i> Species of virus

Brome mosaic virus (BMV) is a small, positive-stranded, icosahedral RNA plant virus belonging to the genus Bromovirus, family Bromoviridae, in the Alphavirus-like superfamily.

<i>Semliki Forest virus</i> Species of virus

The Semliki Forest virus is an alphavirus found in central, eastern, and southern Africa. It was first isolated from mosquitoes in the Semliki Forest, Uganda by the Uganda Virus Research Institute in 1942 and described by Smithburn and Haddow. It is known to cause disease in animals and humans.

<i>Alphavirus</i> Genus of viruses

Alphavirus is a genus of RNA viruses, the sole genus in the Togaviridae family. Alphaviruses belong to group IV of the Baltimore classification of viruses, with a positive-sense, single-stranded RNA genome. There are 32 alphaviruses, which infect various vertebrates such as humans, rodents, fish, birds, and larger mammals such as horses, as well as invertebrates. Alphaviruses that could infect both vertebrates and arthropods are referred dual-host alphaviruses, while insect-specific alphaviruses such as Eilat virus and Yada yada virus are restricted to their competent arthropod vector. Transmission between species and individuals occurs mainly via mosquitoes, making the alphaviruses a member of the collection of arboviruses – or arthropod-borne viruses. Alphavirus particles are enveloped, have a 70 nm diameter, tend to be spherical, and have a 40 nm isometric nucleocapsid.

<i>Thogotovirus</i> Genus of viruses

Thogotovirus is a genus of enveloped RNA viruses, one of seven genera in the virus family Orthomyxoviridae. Their single-stranded, negative-sense RNA genome has six or seven segments. Thogotoviruses are distinguished from most other orthomyxoviruses by being arboviruses – viruses that are transmitted by arthropods, in this case usually ticks. Thogotoviruses can replicate in both tick cells and vertebrate cells; one subtype has also been isolated from mosquitoes. A consequence of being transmitted by blood-sucking vectors is that the virus must spread systemically in the vertebrate host – unlike influenza viruses, which are transmitted by respiratory droplets and are usually confined to the respiratory system.

<i>Orbivirus</i> Genus of viruses

Orbivirus is a genus of double-stranded RNA viruses in the family Reoviridae and subfamily Sedoreovirinae. Unlike other reoviruses, orbiviruses are arboviruses. They can infect and replicate within a wide range of arthropod and vertebrate hosts. Orbiviruses are named after their characteristic doughnut-shaped capsomers.

<i>Sindbis virus</i> Species of virus

Sindbis virus (SINV) is a member of the Togaviridae family, in the Alphavirus genus. The virus was first isolated in 1952 in Cairo, Egypt. The virus is transmitted by mosquitoes. SINV is linked to Pogosta disease (Finland), Ockelbo disease (Sweden) and Karelian fever (Russia). In humans, the symptoms include arthralgia, rash and malaise. Sindbis virus is widely and continuously found in insects and vertebrates in Eurasia, Africa, and Oceania. Clinical infection and disease in humans however has almost only been reported from Northern Europe, where SINV is endemic and where large outbreaks occur intermittently. Cases are occasionally reported in Australia, China, and South Africa.

<i>Orthobunyavirus</i> Genus of viruses

Orthobunyavirus is a genus of the Peribunyaviridae family in the order Bunyavirales. There are currently ~170 viruses recognised in this genus. These have been assembled into 103 species and 20 serogroups.

Mayaro virus disease is a mosquito-borne zoonotic pathogen endemic to certain humid forests of tropical South America. Infection with Mayaro virus causes an acute, self-limited dengue-like illness of 3–5 days' duration. The causative virus, abbreviated MAYV, is in the family Togaviridae, and genus Alphavirus. It is closely related to other alphaviruses that produce a dengue-like illness accompanied by long-lasting arthralgia. It is only known to circulate in tropical South America.

Batai orthobunyavirus (BATV) is a RNA virus belonging to order Bunyavirales, genus Orthobunyavirus.

<i>Quaranjavirus</i> Genus of viruses

Quaranjavirus is a genus of enveloped RNA viruses, one of seven genera in the virus family Orthomyxoviridae. The genome is single-stranded, negative-sense segmented RNA, generally with six segments. The genus contains two species: Johnston Atoll virus and Quaranfil virus; it has been proposed to contain species or strains including Cygnet River virus, Lake Chad virus, Tyulek virus and Wellfleet Bay virus. Quaranjaviruses predominantly infect arthropods and birds; As of March 2015, Quaranfil quaranjavirus is the only member of the genus to have been shown to infect humans. The Quaranfil and Johnston Atoll viruses are transmitted between vertebrates by ticks, resembling members of Thogotovirus, another genus of Orthomyxoviridae.

<i>Nodamura virus</i> Species of virus

Nodamura virus (NoV) is a member of the family Nodaviridae, which was originally isolated from mosquitoes in Japan near the village of Nodamura in 1956. Other members of Nodaviridae are flock house virus (FHV) and black beetle virus (BBV). NoV has been found to multiply in several insect and tick species; however, these infected individuals seem to be asymptomatic. Nodamura virus is the only member of the genus Alphanodavirus that can infect insects, fish, and mammals.

Spondweni virus is an arbovirus, or arthropod-borne virus, which is a member of the family Flaviviridae and the genus Flavivirus. It is part of the Spondweni serogroup which consists of the Sponweni virus and the Zika virus (ZIKV). The Spondweni virus was first isolated in Nigeria in 1952, and ever since, SPONV transmission and activity have been reported throughout Africa. Its primary vector of transmission is the sylvatic mosquito Aedes circumluteolus, though it has been isolated from several different types of mosquito. Transmission of the virus into humans can lead to a viral infection known as Spondweni fever, with symptoms that include headache, nausea, myalgia and arthralgia. However, as SPONV is phylogenetically close to the ZIKV, it is commonly misdiagnosed as ZIKV along with other viral illnesses.

<i>Middelburg virus</i> Species of virus

Middelburg virus (MIDV) is an alphavirus of the Old World Group that has likely endemic and zoonotic potential. It is of the viral family Togaviridae. It was isolated from mosquitos in 1957 in South Africa, MDIV antigens have now been found in livestock, horses, and humans.

Umatilla virus(UMAV) is a dsRNA virus in the family Reoviridae, subfamily Sedoreovirinae, and the genus Orbivirus. This arbovirus was first isolated in 1969 in Umatilla County, Oregon in a group of Culex pipiens mosquitoes. The viral host is the Passer domesticus bird with the vectors being Culex mosquitoes.

<i>Sepik virus</i> Mosquito transmitted virus endemic to Papua New Guinea

Sepik virus (SEPV) is an arthropod-borne virus (arbovirus) of the genus Flavivirus and family Flaviviridae. Flaviviridae is one of the most well characterized viral families, as it contains many well-known viruses that cause diseases that have become very prevalent in the world, like Dengue virus. The genus Flavivirus is one of the largest viral genera and encompasses over 50 viral species, including tick and mosquito borne viruses like Yellow fever virus and West Nile virus. Sepik virus is much less well known and has not been as well-classified as other viruses because it has not been known of for very long. Sepik virus was first isolated in 1966 from the mosquito Mansoniaseptempunctata, and it derives its name from the Sepik River area in Papua New Guinea, where it was first found. The geographic range of Sepik virus is limited to Papua New Guinea, due to its isolation.

Rio Negro virus is an alphavirus that was first isolated in Argentina in 1980. The virus was first called Ag80-663 but was renamed to Rio Negro virus in 2005. It is a former member of the Venezuelan equine encephalitis complex (VEEC), which are a group of alphaviruses in the Americas that have the potential to emerge and cause disease. Río Negro virus was recently reclassified as a distinct species. Closely related viruses include Mucambo virus and Everglades virus.

References

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