Orthobunyavirus


Orthobunyavirus is a genus of the Peribunyaviridae family in the order Elliovirales. The genus contains 138 species.
The name Orthobunyavirus derives from Bunyamwera, Uganda, where Bunyamwera virus was first discovered, along with the prefix meaning 'straight.'

Virology

  • The virus is spherical, diameter 80 nm to 120 nm, and comprises three negative-sense single stranded RNA molecules encapsulated in a ribonucleocapsid.
  • The three RNAs are described as S, M and L and are circa 1kb, 4.5kb and 6.9kb in length
  • The S RNA encodes the Nucleocapsid protein and a non structural protein.
  • The M RNA encodes a polyprotein which is cleaved by host protease into Gn, NSm and Gc proteins.
  • The L RNA encodes the viral RNA dependent RNA Polymerase or L Protein

Life cycle

Vectors

The primary vectors of orthobunyaviruses are hematophagous insects of the Culicidae family, including members from a number of mosquito genera and biting midges. Although transmission by ticks and bed bugs may also occur. Viral vector preference is generally strict, with only a one or very small number of vectors transmitting a specific virus in the region, even where multiple viruses and vectors overlap. Organisms related to the preferential vector may be able to carry a virus but not competently transmit it.
The vector arthropod acquires the virus while taking a blood meal from an infected host. In mosquitoes, replication of orthobunyaviruses is enhanced by immune modulation that occurs as a result of blood protein digestion producing GABA and the activation of GABAergic signalling. Infection is transmitted to a new host via viral particles in vector saliva. Orthobunyavirus infection in arthropod cells is not fully understood, but is generally non-cytopathological and deleterious effects are minimal. Infected mosquitoes may experience an increase in fitness. Transorvarial transmission has been observed among mosquitoes infected with orthobunyaviruses of the California serogroup Like mosquitoes, only female culicoid midges feed on blood; they prefer indoor feeding particularly during rain.

Sylvatic cycle hosts

In the sylvatic cycle, viruses are transmitted between mammalian hosts by the arthropod vector. A diverse range of mammals have been identified or implicated as hosts or reservoirs of orthobunyaviruses including: non-human primates, sloths, wild and domestic birds, marmosets, rodents, and large mammals such as deer, moose, and elk.

Infection

Infection begins with the bite of an infected competent vector organism. Viral entry proceeds by receptor-mediated endocytosis, but which receptors unknown. Although, Heparan sulfate and DC-SIGN have been identified as viral entry components in some orthobunyaviruses. Gn/Gc heterodimers on the viral surface are responsible for target cell recognition, with Gc is considered the primary attachment protein, although Gn has been suggested as the attachment protein for LACV in arthropod cells. Acidification of the endosome triggers a conformational change in the Gc fusion peptide, uncoating the ribonuclearprotein as it is released into the cytoplasm.
Upon release into the cytoplasm, primary transcription begins with an endonuclease domain on L protein engaging in a process known as "cap-snatching." During cap-snatching, 10-18 nucleotides of 5' 7-methylguanylate primers are cleaved from host mRNAs and attached to prime the 5' end of the viral RNAs. Like all negative-sense RNA viruses, orthobunyaviruses require ongoing, concurrent translation by the host cell to produce full-length viral mRNAs, consequently the 3' end of orthobunyavirus mRNAs lack polyadenylation. Notably they are also missing the signal for polyadenylation; instead the 3' ends are thought to form a stem-loop structure. Antigenomes used as templates for replication of the viral genome are produced by L protein RdRp without the need for primers. Both negative-sense genomes and positive-sense antigenomes are associated with N proteins at all times during the replication cycle. Thus, N and L are the minimum proteins required for transcription and replication
The M genome segment codes for the Gn-NSm-Gc polyprotein on a single open-reading frame which is cotranslationally cleaved by internal signal peptides and host signal peptidase. The free glycoproteins Gc and Gn insert into the membrane of the endoplasmic reticulum and form heterodimers. A Golgi retention signal on Gn, permits transport of the heterodimers to the Golgi apparatus, where glycosylation occurs. The presence of the viral glycoproteins modifies the Golgi membrane to enable budding of RNPs into a Golgi derived tubular viral factory. As segmented viruses, orthobuynaviruses require precise packaging of one of each of the three genomic segments into the final virion to produce a mature, infectious particle. Packaging appears to be directed by signals contained entirely within UTR sequences. The packaged genomes acquire a lipid membrane as they bud into the viral factories, are then transported to the host cell plasma membrane and released via exocytosis. A final gylcoprotein modification upon release produces a mature, infectious particle.

Evolution

Orthobunyaviruses evolve partly by a key mechanism known as genomic reassortment, which also occurs in other segmented viruses. When viruses of the same group co-infect a host cell, mixtures and novel combinations of the S, M, and L segments can be produced, increasing diversity. The most common reassortment events are with the L and S segments.

Species

The genus contains the following species, listed by scientific name and followed by the exemplar virus of the species:Orthobunyavirus abrasense, Abras virusOrthobunyavirus acaraense, Acará virusOrthobunyavirus achiotei, Trivittatus virusOrthobunyavirus ainoense, Aino virusOrthobunyavirus akabaneense, Akabane virusOrthobunyavirus anadyrense, Anadyr virusOrthobunyavirus ananindeuaense, Ananindeua virusOrthobunyavirus angeloense, San Angelo virusOrthobunyavirus anhembiense, Anhembi virusOrthobunyavirus apeuense, Apeú virusOrthobunyavirus baakalense, Baakal virusOrthobunyavirus bakauense, Bakau virusOrthobunyavirus balagoduense, Balagodu virusOrthobunyavirus barritaense, Barrita virusOrthobunyavirus bataiense, Batai virusOrthobunyavirus batamaense, Batama virusOrthobunyavirus belemense, Belém virusOrthobunyavirus bellavistaense, Bellavista virusOrthobunyavirus belmontense, Belmont virusOrthobunyavirus benficaense, Benfica virusOrthobunyavirus bertiogaense, Bertioga virusOrthobunyavirus biraoense, Birao virusOrthobunyavirus bobayaense, Bobaya virusOrthobunyavirus boraceiaense Boracéia virusOrthobunyavirus botambiense, Botambi virusOrthobunyavirus bozoense, Bozo virusOrthobunyavirus brazoriaense, Brazoran virusOrthobunyavirus bruconhaense, Bruconha virusOrthobunyavirus buffaloense, Buffalo Creek virusOrthobunyavirus bunyamweraense, Bunyamwera virusOrthobunyavirus bushbushense, Bushbush virusOrthobunyavirus buttonwillowense, Buttonwillow virusOrthobunyavirus bwambaense, Bwamba virusOrthobunyavirus cacheense, Cache Valley virusOrthobunyavirus capimense, Capim virusOrthobunyavirus caraparuense, Caraparú virusOrthobunyavirus catqueense, Cát Quế virusOrthobunyavirus catuense, Catú virusOrthobunyavirus cuchillaense, Anopheles B virusOrthobunyavirus ebiense, Ebinur Lake virusOrthobunyavirus encephalitidis, California encephalitis virusOrthobunyavirus enseadaense, Enseada virusOrthobunyavirus faceyense, Facey's paddock virusOrthobunyavirus gamboaense, Gamboa virusOrthobunyavirus ganganense, Gan Gan virusOrthobunyavirus guajaraense, Guajará virusOrthobunyavirus guamaense, Guamá virusOrthobunyavirus guaratubaense, Guaratuba virusOrthobunyavirus guaroaense, Guaroa virusOrthobunyavirus gumbolimboense, Gumbo Limbo virusOrthobunyavirus heptayabaense, Yaba-7 virusOrthobunyavirus horizonteense, Anopheles A virusOrthobunyavirus iacoense, Iaco virusOrthobunyavirus ileshaense, Ilesha virusOrthobunyavirus indianense, I612045 virusOrthobunyavirus infirmati, Infirmatus virusOrthobunyavirus ingwavumaense, Ingwavuma virusOrthobunyavirus insulae, Kairi virusOrthobunyavirus jamestownense, Jamestown Canyon virusOrthobunyavirus jatobalense, Jatobal virusOrthobunyavirus juandiazense, Juan Díaz virusOrthobunyavirus kaengkhoiense, Kaeng Khoi virusOrthobunyavirus kernense, Main Drain virusOrthobunyavirus ketapangense, Ketapang virusOrthobunyavirus keystoneense, Keystone virusOrthobunyavirus khatangaense, Snowshoe hare virusOrthobunyavirus koongoli, Koongol virusOrthobunyavirus kowanyamaense, Kowanyama virusOrthobunyavirus lacrosseense, La Crosse virusOrthobunyavirus lasmaloyasense, Las Maloyas virusOrthobunyavirus leanyerense, Leanyer virusOrthobunyavirus ledniceense, Lednice virusOrthobunyavirus lichuanense, Lichuan virusOrthobunyavirus lukuniense, Lukuni virusOrthobunyavirus lumboense, Lumbo virusOrthobunyavirus macauaense, Macauã virusOrthobunyavirus madridense, Madrid virusOrthobunyavirus maguariense, Maguari virusOrthobunyavirus mahoganyense, Mahogany Hammock virusOrthobunyavirus manzanillaense, Manzanilla virusOrthobunyavirus maprikense, Maprik virusOrthobunyavirus maritubaense, Marituba virusOrthobunyavirus matruhense, Matruh virusOrthobunyavirus melajoense, Melao virusOrthobunyavirus mermetense, Mermet virusOrthobunyavirus minatitlanense, Minatitlán virusOrthobunyavirus mirimense, Mirim virusOrthobunyavirus mitchellense, Mapputta virusOrthobunyavirus mpokoense, M'Poko virusOrthobunyavirus navioense, Serra do Navio virusOrthobunyavirus nepuyoi, Nepuyo virusOrthobunyavirus nesszionaense, Ness Ziona virusOrthobunyavirus nolaense, Nola virusOrthobunyavirus northwayense, Northway virusOrthobunyavirus nyandoense, Nyando virusOrthobunyavirus okolaense, Okola virusOrthobunyavirus olifantsvleiense, Olifantsvlei virusOrthobunyavirus oribocaense, Oriboca virusOrthobunyavirus oropoucheense, Oropouche virusOrthobunyavirus oyoense, Oyo virusOrthobunyavirus pacoraense, Pacora virusOrthobunyavirus parkeri, Parker's Farm virusOrthobunyavirus patoisense, Patois virusOrthobunyavirus peachesterense, Peaton virusOrthobunyavirus porteiraense, Cachoeira Porteira virusOrthobunyavirus potosiense, Potosi virusOrthobunyavirus saboense, Sabo virusOrthobunyavirus sangoense, Sango virusOrthobunyavirus sanjuanense, San Juan virusOrthobunyavirus schmallenbergense, Schmallenberg virusOrthobunyavirus sedlecense, Sedlec virusOrthobunyavirus shermanense, Fort Sherman virusOrthobunyavirus shokweense, Shokwe virusOrthobunyavirus shuniense, Shuni virusOrthobunyavirus simbuense, Simbu virusOrthobunyavirus sororocaense, Sororoca virusOrthobunyavirus squalofluvii, Shark River virusOrthobunyavirus sussexense, Little Sussex virusOrthobunyavirus tacaiumaense, Tacaiuma virusOrthobunyavirus tahynaense, Ťahyňa virusOrthobunyavirus taiense, Tai orthobunyavirus Orthobunyavirus tangaense, Tanga virusOrthobunyavirus taniyamense, Taniyama virusOrthobunyavirus tataguineense, Tataguine virusOrthobunyavirus telokense, Telok Forest virusOrthobunyavirus tensawense, Tensaw virusOrthobunyavirus termeilense, Termeil virusOrthobunyavirus teteense, Tete virusOrthobunyavirus thimiriense, Thimiri virusOrthobunyavirus timboteuaense, Timboteua virusOrthobunyavirus trinitiense, Triniti virusOrthobunyavirus turlockense, Turlock virusOrthobunyavirus umbreense, Umbre virusOrthobunyavirus utingaense, Utinga virusOrthobunyavirus witwatersrandense, Witwatersrand virusOrthobunyavirus wolkbergense, Wolkberg virusOrthobunyavirus wyeomyiae, Wyeomyia virusOrthobunyavirus yacaabaense, Yacaaba virus