Bluetongue disease or catarrhal fever is a non-contagious, insect-borne viral disease of ruminants, mainly sheep and less frequently of cattle, goats, buffalo, deer, dromedaries and antelope. It is caused by the Bluetongue virus.
Bluetongue is caused by the pathogenic virus, Bluetongue virus (BTV), of the genus Orbivirus, is a member of the Reoviridae family. There are 24 serotypes. It is transmitted by a midge, Culicoides imicola and other culicoids.
BTV is the type species of the genus Orbivirus within the family Reoviridae. The Reoviridae family is one of the largest families of viruses and includes major human pathogens (e.g., rotavirus) as well as other vertebrate, plant and insect pathogens. Like the other members of the family, Orbiviruses which encompass, besides BTV, the agents causing African horse sickness (AHSV) and epizootic hemorrhagic disease of deer (EHDV), have the characteristic double-stranded and segmented features of their RNA genomes. However, unlike the mammalian reoviruses, Orbiviruses comprising 14 serogroups, are vectored to a variety of vertebrates by arthropod species (e.g., gnats, mosquitoes and ticks) and replicate in both hosts. BTV, the etiological agent of Bluetongue disease of animals, is transmitted by Culicoides species. 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 (e.g., blesbuck, white-tailed deer, elk, pronghorn antelope, etc.). The disease was first described in the late 18th century and was believed for many decades to be confined to Africa. However, to date BTV has been isolated in many tropical, subtropical and temperate zones and 24 serotypes have been identified from different parts of the world. Due to its economic significance BTV has been the subject of extensive molecular, genetic and structural studies. As a consequence it now represents one of the best characterised viruses.
Unlike the reovirus and rotavirus particles, the mature BTV particle is relatively fragile and the infectivity of BTV is lost easily in mildly acidic conditions. BTV virions (550S) are architecturally complex structures composed of 7 discrete proteins that are organised into two concentric shells, the outer and inner capsids, and a genome of 10 dsRNA segments. The outer capsid, which is composed of two major structural proteins (VP2 and VP5), is involved in cell attachment and virus penetration during the initial stages of infection. Shortly after infection, BTV is uncoated, i.e. VP2 and VP5 are removed, to yield 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.
Despite these advances, some critical questions remain unanswered for the BTV life cycle and a more complete understanding of the interactions between the virus and the host cell is required for these to be addressed. For example, although progress has been made in the identification of signals for the recruitment of BTV RNA segments into the virion assembly site in the host cell cytoplasm, it has not been possible yet to determine how exactly each genome segment is packaged into the progeny virus. It is also not apparent when and how these genome segments wrap around the polymerase complex once the RNA has been recruited. One of the major drawbacks of research with BTV and other members of Reoviridae has been the lack of availability of a suitable system for genetic manipulation of the virus. This has been a major obstacle in understanding the replication processes of these viruses. However, one of the recent developments in the field of BTV research has been to rescue live virus from transfection of BTV transcripts. There is no doubt that this will be soon extended to establish in vitro manipulative genetic system and will be utilized to address some of these remaining questions.
Very little is known of the intracellular trafficking of newly generated virions although there are some indications of involvement of the cytoskeleton, intermediate filaments and vimentin during BTV morphogenesis. Host–virus interactions during virus trafficking will be one of the future areas needing intense attention. Recent work has revealed unexpected and striking parallels between the entry and release pathways of BTV and pathways involved in entry and release of enveloped viruses. These parallels may be the result of an enveloped ancestor virus or because there are a limited number of cellular pathways that can be useful for the egress of large protein complexes from cells. It is notable that the NS3 glycoprotein of BTV is an integral membrane protein that is functionally involved in virus egress by bridging between the outer capsid protein VP2 and the cellular export machinery. Although no cell-free enveloped form of BTV has been isolated, budding of BTV particles from infected cells at the plasma membrane are quite apparent. The exact role of NS3 in this process and the role of host proteins (Annexin II and p11, Tsg101 and MVB) and their contribution in the release of non-enveloped viruses, such as BTV, remains to be clarified.
It was previously believed that only special lab-raised BTV were capable of transplacental infection. Experiments on sheep in the 1970s showed that such infection would result in abortion or weak or deformed offspring, with some offspring carrying the virus in their bloodstream. Such damage to the offspring was also seen for the calves born in Northern Ireland.
Nasal symptoms 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".
Not all animals develop symptoms, but all those that do lose condition rapidly, and the sickest die within a week. For affected animals which do not die, recovery is very slow, lasting several months.
The incubation period is 5–20 days, and all symptoms 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 percent.
However, simple husbandry changes and practical midge control measures may help break the livestock infection cycle. Housing livestock during times of maximum midge activity (from dusk to dawn) may lead to significantly reduced biting rates. Similarly, protecting livestock shelters with fine mesh netting or coarser material impregnated with insecticide will reduce contact with the midges. The Culicoides midges that carry the virus usually breed on animal dung and moist soils, either bare or covered in short grass. Identifying breeding grounds and breaking the breeding cycle will significantly reduce the local midge population. Turning off taps, mending leaks and filling in or draining damp areas will also help dry up breeding sites. Dung heaps and straw bedding should be removed at least weekly to break the midge breeding cycle.