Bluetongue virus | |
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Electron micrograph of Bluetongue virus, cale bar = 50 nm | |
Virus classification | |
(unranked): | Virus |
Realm: | Riboviria |
Kingdom: | Orthornavirae |
Phylum: | Duplornaviricota |
Class: | Resentoviricetes |
Order: | Reovirales |
Family: | Sedoreoviridae |
Genus: | Orbivirus |
Species: | Bluetongue virus |
Bluetongue disease is a noncontagious, insect-borne, viral disease of ruminants, mainly sheep and less frequently cattle, [1] yaks, [2] goats, buffalo, deer, dromedaries, and antelope. It is caused by Bluetongue virus (BTV). The virus is transmitted by the midges Culicoides imicola , Culicoides variipennis , and other culicoids.
In sheep, BTV causes an acute disease with high morbidity and mortality. BTV also infects goats, cattle, and other domestic animals, as well as wild ruminants (for example, blesbuck, white-tailed deer, elk, and pronghorn antelope). [3]
Major signs are high fever, excessive salivation, swelling of the face and tongue, and cyanosis of the tongue. Swelling of the lips and tongue gives the tongue its typical blue appearance, though this sign is confined to a minority of the animals. Nasal signs may be prominent, with nasal discharge and stertorous respiration.
Some animals also develop foot lesions, beginning with coronitis, with consequent lameness. In sheep, this can lead to knee-walking. In cattle, constant changing of position of the feet gives bluetongue the nickname the dancing disease. [4] Torsion of the neck (opisthotonos or torticollis) is observed in severely affected animals.
Not all animals develop signs, but all those that do lose condition rapidly, and the sickest die within a week. For affected animals that do not die, recovery is very slow, lasting several months.
The incubation period is 5–20 days, and all signs usually develop within a month. The mortality rate is normally low, but it is high in susceptible breeds of sheep. In Africa, local breeds of sheep may have no mortality, but in imported breeds, it may be up to 90%. [5]
In cattle, goats, and wild ruminants, infection is usually asymptomatic despite high virus levels in blood. Red deer are an exception, and in them the disease may be as acute as in sheep. [6]
Bluetongue is caused by the pathogenic virus, Bluetongue virus (BTV), [3] of the genus Orbivirus , of the Reoviridae family. Twenty-seven serotypes are now recognised for this virus. [7] The twenty-seven serotypes are the result of the high variability of a single outer capsid protein, VP2.
The virus particle consists of 10 strands of double-stranded RNA surrounded by two protein shells. Unlike other arboviruses, BTV lacks a lipid envelope. The particle has a diameter of 86 nm. [8] The structure of the 70 nm core was determined in 1998 and was at the time the largest atomic structure to be solved. [9]
The two outer capsid proteins, VP2 and VP5, mediate attachment and penetration of BTV into the target cell. VP2 and VP5 are the primary antigenic targets for antibody targeting by the host immune system. The virus makes initial contact with the cell with VP2, triggering receptor-mediated endocytosis of the virus. The low pH within the endosome then triggers BTV's membrane penetration protein VP5 to undergo a conformational change that disrupts the endosomal membrane. [8] Uncoating yields a transcriptionally active 470S core particle which is composed of two major proteins VP7 and VP3, and the three minor proteins VP1, VP4 and VP6 in addition to the dsRNA genome. There is no evidence that any trace of the outer capsid remains associated with these cores, as has been described for reovirus. The cores may be further uncoated to form 390S subcore particles that lack VP7, also in contrast to reovirus. Subviral particles are probably akin to cores derived in vitro from virions by physical or proteolytic treatments that remove the outer capsid and causes activation of the BTV transcriptase. In addition to the seven structural proteins, three non-structural (NS) proteins, NS1, NS2, NS3 (and a related NS3A) are synthesised in BTV-infected cells. Of these, NS3/NS3A is involved in the egress of the progeny virus. The two remaining non-structural proteins, NS1 and NS2, are produced at high levels in the cytoplasm and are believed to be involved in virus replication, assembly and morphogenesis. [3]
The viral genome is replicated via structural protein VP1, an RNA-dependent RNA polymerase. [7] The lack of proof-reading abilities results in high levels of transcription errors, resulting in single nucleotide mutations. Despite this, the BTV genome is quite stable, exhibiting a low rate of variants arising in populations. [10] Evidence suggests this is due to purifying selection across the genome as the virus is transmitted alternately through its insect and animal hosts. [10] However, individual gene segments undergo different selective pressures and some, particularly segments 4 and 5, are subject to positive selection. [10]
Genetic diversification of BTV occurs primarily through reassortment of the gene segments during co-infection of the host cell. Reassortment can lead to a rapid shift in phenotypes independent of the slow rate of mutation. During this process, gene segments are not randomly reassorted. Rather, there appears to be a mechanism for selecting for or against certain segments from the parental serotypes present. [11] However, this selective mechanism is still poorly understood.
Bluetongue has been observed in Australia, the US, Africa, the Middle East, Asia, and Europe. An outline of the transmission cycle of BTV is illustrated in article Parasitic flies of domestic animals.
Its occurrence is seasonal in the affected Mediterranean countries, subsiding when temperatures drop and hard frosts kill the adult midge vectors. [12] Viral survival and vector longevity is seen during milder winters. [13] A significant contribution to the northward spread of bluetongue disease has been the ability of C. obsoletus and C.pulicaris to acquire and transmit the pathogen, both of which are spread widely throughout Europe. This is in contrast to the original C.imicola vector, which is limited to North Africa and the Mediterranean. The relatively recent novel vector has facilitated a far more rapid spread than the simple expansion of habitats north through global warming. [14]
In August 2006, cases of bluetongue were found in the Netherlands, then Belgium, Germany, and Luxembourg. [15] [16] In 2007, the first case of bluetongue in the Czech Republic was detected in one bull near Cheb at the Czech-German border. [17] In September 2007, the UK reported its first ever suspected case of the disease, in a Highland cow on a rare-breeds farm near Ipswich, Suffolk. [18] Since then, the virus has spread from cattle to sheep in Britain. [19] By October 2007, bluetongue had become a serious threat in Scandinavia and Switzerland [20] and the first outbreak in Denmark was reported. [21] In autumn 2008, several cases were reported in the southern Swedish provinces of Småland, Halland, and Skåne, [22] as well as in areas of the Netherlands bordering Germany, prompting veterinary authorities in Germany to intensify controls. [23] Norway had its first finding in February 2009, when cows at two farms in Vest-Agder in the south of Norway showed an immune response to bluetongue. [24] Norway was declared free of the disease in 2011. [25] As of November 2023, cases of bluetongue have been recorded in Belgium, Germany, the Netherlands, France, Spain, and the UK. [26]
Although the disease is not a threat to humans, the most vulnerable common domestic ruminants are cattle, goats, and especially, sheep.
A puzzling aspect of BTV is its survival between midge seasons in temperate regions. Adults of Culicoides are killed by cold winter temperatures, and BTV infections typically do not last for more than 60 days, which is not long enough for BTV to survive until the next spring. It is believed that the virus somehow survives in overwintering midges or animals. Multiple mechanisms have been proposed. A few adult Culicoides midges infected with BTV may survive the mild winters of the temperate zone. Some midges may even move indoors to avoid the cold temperature of the winter. Additionally, BTV could cause a chronic or latent infection in some animals, providing another means for BTV to survive the winter. BTV can also be transmitted from mother to fetus. The outcome is abortion or stillbirth if fetal infection occurs early in gestation and survival if infection occurs late. However infection at an intermediate stage, before the fetal immune system is fully developed, may result in a chronic infection that lingers until the first months after birth of the lamb. Midges then spread the pathogen from the calves to other animals, starting a new season of infection. [27]
Prevention is effected via quarantine, inoculation with live modified virus vaccine, and control of the midge vector, including inspection of aircraft.
Protection by live attenuated vaccines (LAVs) are serotype specific. Multiserotype LAV cocktails can induce neutralizing antibodies against unincluded serotypes, and subsequent vaccinations with three different pentavalent LAV cocktails induce broad protection. These pentavalent cocktails contain 15 different serotypes in total: serotypes 1 through 14, as well as 19. [32]
Immunization with any of the available vaccines, though, precludes later serological monitoring of affected cattle populations, a problem that could be resolved using next-generation subunit vaccines. [33]
In January 2015, Indian researchers launched a vaccine named Raksha Blu that is designed to protect livestock against five strains of the bluetongue virus prevalent in the country. [34]
Although bluetongue disease was already recognized in South Africa in the early 19th century, a comprehensive description of the disease was not published until the first decade of the 20th century. [35] In 1906, Arnold Theiler showed that bluetongue was caused by a filterable agent. He also created the first bluetongue vaccine, which was developed from an attenuated BT [36] V strain. [37] For many decades, bluetongue was thought to be confined to Africa. The first confirmed outbreak outside of Africa occurred in Cyprus in 1943. [35] Recently, a vessel owned by Khalifeh Livestock Trading and managed by Talia Shipping Line, both based in Lebanon, has been denied right to dock in Spain, as it has about 895 male calves suspected to be infected by bluetongue disease. [36] [38]
African horse sickness is related to bluetongue and is spread by the same midges (Culicoides species). It can kill the horses it infects and mortality may go as high as 90% of the infected horses during an epidemic. [39]
Epizootic hemorrhagic disease virus is closely related and crossreacts with Bluetongue virus on many blood tests.
Rift Valley fever (RVF) is a viral disease of humans and livestock that can cause mild to severe symptoms. The mild symptoms may include: fever, muscle pains, and headaches which often last for up to a week. The severe symptoms may include: loss of sight beginning three weeks after the infection, infections of the brain causing severe headaches and confusion, and bleeding together with liver problems which may occur within the first few days. Those who have bleeding have a chance of death as high as 50%.
Foot-and-mouth disease virus (FMDV) is the pathogen that causes foot-and-mouth disease. It is a picornavirus, the prototypical member of the genus Aphthovirus. The disease, which causes vesicles (blisters) in the mouth and feet of cattle, pigs, sheep, goats, and other cloven-hoofed animals is highly infectious and a major plague of animal farming.
Culicoides imicola is a species of Ceratopogonidae that transmits the bluetongue virus (BTV) and the African horse sickness virus. This particular species has been recorded in Africa, Asia and Europe. African midges feed on animal blood, including horse, cattle, and sheep. Unlike other species within the Culicoides genus, this species prefers drier habitats for egg laying but retains a preference for moist soil to support larvae growth. Other suspected BTV vectors are Culicoides (Culicoides) pulicaris and species in the Culicoides (Avaritia) obsoletus complex.
Adeno-associated viruses (AAV) are small viruses that infect humans and some other primate species. They belong to the genus Dependoparvovirus, which in turn belongs to the family Parvoviridae. They are small replication-defective, nonenveloped viruses and have linear single-stranded DNA (ssDNA) genome of approximately 4.8 kilobases (kb).
Infectious bursal disease (IBD), also known as Gumboro disease, infectious bursitis, and infectious avian nephrosis, is a highly contagious disease of young chickens and turkeys caused by infectious bursal disease virus (IBDV), characterized by immunosuppression and mortality generally at 3 to 6 weeks of age. The disease was first discovered in Gumboro, Delaware in 1962. It is economically important to the poultry industry worldwide due to increased susceptibility to other diseases and negative interference with effective vaccination. In recent years, very virulent strains of IBDV (vvIBDV), causing severe mortality in chicken, have emerged in Europe, Latin America, South-East Asia, Africa, and the Middle East. Infection is via the oro-fecal route, with affected birds excreting high levels of the virus for approximately 2 weeks after infection. The disease is easily spread from infected chickens to healthy chickens through food, water, and physical contact.
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.
Aphthovirus is a viral genus of the family Picornaviridae. Aphthoviruses infect split-hooved animals, and include the causative agent of foot-and-mouth disease, Foot-and-mouth disease virus (FMDV). There are seven FMDV serotypes: A, O, C, SAT 1, SAT 2, SAT 3 and Asia 1, and four non-FMDV serotypes belonging to three additional species Bovine rhinitis A virus (BRAV), Bovine rhinitis B virus (BRBV) and Equine rhinitis A virus (ERAV).
African horse sickness (AHS) is a highly infectious and often fatal disease caused by African horse sickness virus. It commonly affects horses, mules, and donkeys. It is caused by a virus of the genus Orbivirus belonging to the family Reoviridae. This disease can be caused by any of the nine serotypes of this virus. AHS is not directly contagious, but is known to be spread by insect vectors.
Bovine malignant catarrhal fever (BMCF) is a fatal lymphoproliferative disease caused by a group of ruminant gamma herpes viruses including Alcelaphine gammaherpesvirus 1 (AlHV-1) and Ovine gammaherpesvirus 2 (OvHV-2) These viruses cause unapparent infection in their reservoir hosts, but are usually fatal in cattle and other ungulates such as deer, antelope, and buffalo. In Southern Africa the disease is known as snotsiekte, from the Afrikaans.
Epizootic hemorrhagic disease (EHD) is a hemorrhagic disease of white-tailed deer caused by an infection of a virus from the genus Orbivirus subsequently called Epizootic hemorrhagic disease virus (EHDV). It is an infectious, and sometimes fatal, virus that is characterized by extensive hemorrhages, and is found throughout the United States. Large-scale outbreaks in wild ruminants affect livestock and the production industry. EHD has been found in some domestic ruminants and many species of deer including white-tailed deer, mule deer, elk, and pronghorn antelope. Seropositive black-tailed deer, fallow deer, red deer, wapiti, and roe deer have also been found, which essentially means that they were exposed to the disease at some time in the past but may not be involved in transmission. Outbreaks of EHD have been reported in cattle, although they rarely develop disease or die. Sheep may develop clinical signs, but this is also rare. EHD is often called bluetongue, but this is incorrect. Bluetongue virus is closely related to EHDV, and has similar clinical signs, but it is a different disease. Bluetongue is a serious disease in cattle, as well as other ruminants, and can have a significant effect on international trade. Testing at animal health laboratories is necessary to distinguish between the viruses that cause bluetongue and EHD.
Culicoides is a genus of biting midges in the family Ceratopogonidae. There are over 1000 species in the genus, which is divided into many subgenera. Several species are known to be vectors of various diseases and parasites which can affect animals. The genus has a long fossil record, with earliest known fossils being from Burmese amber, around 99 million years old.
Animal viruses are viruses that infect animals. Viruses infect all cellular life and although viruses infect every animal, plant, fungus and protist species, each has its own specific range of viruses that often infect only that species.
Enterovirus E is a picornavirus of the genus Enterovirus. The virus may also be referred to as enteric cytopathic bovine orphan virus (ECBO). It is endemic in cattle populations worldwide, and although normally fairly nonpathogenic, it can cause reproductive, respiratory, or enteric disease – particularly when the animal is concurrently infected with another pathogen.
Foot-and-mouth disease (FMD) or hoof-and-mouth disease (HMD) is an infectious and sometimes fatal viral disease that affects cloven-hoofed animals, including domestic and wild bovids. The virus causes a high fever lasting two to six days, followed by blisters inside the mouth and near the hoof that may rupture and cause lameness.
Schmallenberg orthobunyavirus, also called Schmallenberg virus, abbreviated SBV, is a virus that causes congenital malformations and stillbirths in cattle, sheep, goats, and possibly alpaca. It appears to be transmitted by midges, which are likely to have been most active in causing the infection in the Northern Hemisphere summer and autumn of 2011, with animals subsequently giving birth from late 2011. Schmallenberg virus falls in the Simbu serogroup of orthobunyaviruses. It is considered to be most closely related to the Sathuperi and Douglas viruses.
Equine encephalosis virus (EEV) is a species of virus the Orbivirus genus, and a member of the Reoviridae family, related to African horse sickness virus (AHSV) and Bluetongue virus (BTV).
Capripoxvirus is a genus of viruses in the subfamily Chordopoxvirinae and the family Poxviridae. Capripoxviruses are among the most serious of all animal poxviruses. All CaPV are notifiable diseases to the OIE. Sheep, goat, and cattle serve as natural hosts. These viruses cause negative economic consequences by damaging hides and wool and forcing the establishment of trade restrictions in response to an outbreak. The genus consists of three species: sheeppox virus (SPPV), goatpox virus (GTPV), and lumpy skin disease virus (LSDV). They share no serological relationship with camel pox, horse pox, or avian poxes. Capripoxviruses for sheeppox and goatpox infect only sheep and goat respectively. However, it is probable that North American relatives, the mountain goat and mountain sheep, may be susceptible to the strains but has not been experimentally proven. Lumpy skin disease virus affects primarily cattle, but studies have been shown that giraffes and impala are also susceptible to LSDV. Humans cannot be infected by Capripoxviruses.
Cache Valley orthobunyavirus (CVV) is a member of the order Bunyavirales, genus Orthobunyavirus, and serogroup Bunyamwera, which was first isolated in 1956 from Culiseta inornata mosquitos collected in Utah's Cache Valley. CVV is an enveloped arbovirus, nominally 80–120 nm in diameter, whose genome is composed of three single-stranded, negative-sense RNA segments. The large segment of related bunyaviruses is approximately 6800 bases in length and encodes a probable viral polymerase. The middle CVV segment has a 4463-nucleotide sequence and the smallest segment encodes for the nucleocapsid, and a second non-structural protein. CVV has been known to cause outbreaks of spontaneous abortion and congenital malformations in ruminants such as sheep and cattle. CVV rarely infects humans, but when they are infected it has caused encephalitis and multiorgan failure.
Epizootic hemorrhagic disease virus, often abbreviated to EHDV, is a species of the genus Orbivirus, a member of the family Reoviridae. It is the causative agent of epizootic hemorrhagic disease, an acute, infectious, and often fatal disease of wild ruminants. In North America, the most severely affected ruminant is the white-tailed deer, although it may also infect mule deer, black-tailed deer, elk, bighorn sheep, and pronghorn antelope. It is often mistakenly referred to as “bluetongue virus” (BTV), another Orbivirus that like EHDV causes the host to develop a characteristic blue tongue due to systemic hemorrhaging and lack of oxygen in the blood. Despite showing clinical similarities, these two viruses are genetically distinct.
Avibirnavirus is a genus of viruses in family Birnaviridae. There is a single species in this genus: Infectious bursal disease virus, which infects chickens and other fowl. It causes severe inflammation of the bursa of Fabricius, and causes considerable morbidity and mortality.