Thogotovirus

[13] Since then, sequence analysis of five viruses discovered in the 1960–70s but unclassified or tentatively assigned to Bunyaviridae led to their being proposed as additional members of the genus.

[23] THOV and JOSV[2] also encode the protein M-long (ML), which counters the host's innate immunity, in particular by suppressing the production of interferon.

This immune evasion is important for the virus to infect systemically in vertebrates, but is unnecessary in arthropods, which lack the interferon response.

[15][16] In some members of the genus, replication has been shown to be sensitive to the Mx1/MxA protein, which is induced in mice and humans in response to interferon.

[9][26] In one study, this inhibitory effect was shown to be caused by MxA preventing the transport of the THOV genome into the nucleus.

[17][21] Most thogotoviruses have been shown to infect arthropods, generally hard or soft ticks, which are arachnids,[7] but in one case mosquitoes, which are insects.

[9] Members also infect birds[15][30] and a wide range of wild and domestic mammals, including marsupials,[14] rodents,[4] hares,[31] mongoose,[32] horses,[6] camels, goats, sheep and cattle.

THOV persists in the tick, remaining in the organism as it goes through its developmental stages; this is called transstadial transmission.

[33] THOV can be transmitted between ticks when they feed simultaneously on apparently uninfected guinea pigs, in the absence of a detectable level of virus in the blood.

[5][36][37][38][39] As of February 2015, only eight cases of human disease associated with thogotoviruses have been reported: two with THOV, five with DHOV and one with Bourbon virus; there have been two fatalities.

[39] The single case of disease in a person infected with Bourbon virus was associated with decreases in blood platelets and white cells; no neurological symptoms were observed.

The antiviral drug ribavirin, which has a broad spectrum of activity that includes some other orthomyxoviruses,[40] has been shown to inhibit DHOV replication in vitro in a single study.

[43] The two viruses have a low degree of sequence identity (37% for the nucleoprotein; 31% for the envelope glycoprotein), and their antibodies do not crossreact.

[7] THOV was first isolated from ticks gathered from cattle in the Thogoto Forest region of Kenya, near Nairobi, in 1960,[5] it is now known to be distributed across the African continent, and has also been found in Italy and Portugal in Europe, and Iran in the Middle East.

[5][13][19][31][45] Antibodies have been found to THOV in rats and many domestic animals, including goats, sheep, donkeys, camels, cattle and buffaloes, and the virus has been isolated from the wild banded mongoose (Mongos mungo).

[7][15] No natural vertebrate host has been identified, but the virus is highly pathogenic to mice in laboratory infections.

[15] UPOV was first isolated on Upolu Cay in the Great Barrier Reef, Australia in 1966, from soft-bodied ticks of the species Ornithodoros capensis associated with the sooty tern (Onychoprion fuscatus).

No natural vertebrate host has been identified, but the virus is highly pathogenic to mice in laboratory infections.

[15] DHOV was first isolated from Hyalomma dromedarii hard-bodied ticks infesting camels in Gujarat, India, in 1961.

[6][13][31][46][47] Where DHOV is prevalent, antibodies to the virus have been documented in camels, goats, horses, cattle and humans.

[31][48] DHOV can infect humans by the aerosol route after accidental laboratory exposure, causing a febrile illness and encephalitis.

[9][30] It has also been found to infect mosquitoes of the species Aedes caspius Pallas and Culex hortensis Ficalbi, also in Kyrgyzstan.

[50] Its geographical range is limited to Central Asia, Transcaucasia and the area to the north of the Caspian Sea.

[9] Batken is considered a DHOV subtype; the viruses have a high degree of sequence identity (90% in the envelope glycoprotein; 96–98% in other proteins), and their antibodies crossreact.

The virus is variable in shape, with filamentous as well as spherical forms; it has a diameter broadly in the range 100–130 nm.

[7] Oz virus was first characterised in 2018 after isolation from the hard tick Amblyomma testudinarium in Ehime, Japan.

The first human case, a 70 year old female patient who died of myocarditis with isolation of Oz virus on autopsy, was reported on 23.6.2023 by the Japanese Ministry of Heath.

Schematic drawing of a virion (genera Thogotovirus and Quaranjavirus , cross section)
Thogotovirus genome map
Predicted structure of THOV glycoprotein (left) compared with GP64 of the baculovirus, Autographa californica multicapsid nucleopolyhedrovirus (right)
Electron micrograph showing endocytosis (arrows) of Bourbon virus (scale bar: 100 nm)
Phylogeny of selected orthomyxoviruses, based on the nucleocapsid protein (scale bar: amino acid substitutions per site)
Hyalomma marginatum is one of the vectors of DHOV
Electron micrograph of a filamentous form of Bourbon virus (scale bar: 100 nm)