Cache Valley Orthobunyavirus
Also known as
Cache Valley Virus (CVV)
Cache Valley Virus (CVV) is a mosquito-borne zoonotic (transmissible to humans) disease syndrome of sheep and possibly all ruminants. It is characterized by embryonic and fetal death, stillbirths, and multiple congenital malformations.
This virus is endemic in Canada, Mexico, and the United States. Several related Bunyaviruses also may play a role in syndromes of congenital malformations and embryonic losses in North America.
Cache Valley virus disease is rarely diagnosed in North America, however, partly because laboratories rarely test for it. Its true incidence and full spectrum of clinical signs is unknown.
Humans are frequently exposed to the virus in endemic regions; some studies show antibody prevalence ranging from 3% to 19%. The development of severe disease occurs only rarely in humans, however, but is potentially life-threatening with symptoms ranging from fever to encephalitis.
CVV is responsible for periodic outbreaks in sheep, causing fetal death and congenital defects in lambs. Fewer problems are seen in cattle.
Virus transmission is unpredictable from year-to-year, possibly due to periodic extinction of certain strains and reintroduction of new virus strains into certain regions. To evaluate this possibility, a group of scientists sequenced and analyzed numerous CVV isolates sampled in Connecticut during an 18-year period to determine how the virus population changes over time.
There was establishment of a new viral lineage during 2010 that became dominant by 2014 and appears to have originated from southern Mexico.
CVV has significant economic impacts in the sheep industry due to fetal malformations such as arthrogryposis (twisted, crooked limbs) and hydrocephalus (water on the brain), embryonic death, and mummification, but severe clinical disease in other livestock and horses appears to be rare.
Two researchers reported the presence of CVV antibodies in cattle that gave birth to calves with arthrogryposis and hydrocephalus in Saskatchewan, but CVV prevalence in that cattle population was unknown and the association of CVV with those birth defects was unsubstantiated.
“Open” dams due to embryo loss and abortion, and fetuses with malformations in musculoskeletal system and central nervous system, are the major clinical signs of the disease.
The fetuses show arthrogryposis--curled, twisted, and crooked limbs—and sometimes a deviation of the spinal cord (scoliosis) or torticollis (contractures of neck muscles causing the head to be bent down or twisted to one side).
Central nervous system changes include varying degrees of hydranencephaly (a condition in which the cerebral hemispheres of the brain are absent and the remaining cranial cavity is filled with cerebrospinal fluid).
The cerebrum may be missing or under-developed, and the fetus may have generalized muscle atrophy.
- Congenital defects
Cache Valley virus (CVV), is a member of the Bunyamwera serogroup (family Bunyaviridae, genus Orthobunyavirus) and geographically widespread in North America, where it circulates between mosquitoes and mammals. It has been associated mainly with sheep, with only a few cases of human disease. It is occasionally seen in cattle.
Throughout much of North and Central America the virus circulates in a cycle involving mammal-biting mosquitoes and deer hosts. This virus has been found in caribou, horses, sheep, cattle, and other domestic and wild animals and is considered endemic in North America, the Caribbean, and Argentina.
It is transmitted through the bites of mosquitoes and culicoid midges and considered an indirect disease in humans and livestock; infection occurs through mosquito bites and not through direct contact with infected domestic or wild animals.
Although other viruses belonging to the Bunyamwera serogroup occur in the United States, such as the Potosi virus, Main Drain virus, Lokern virus, Tensaw virus, and Northway virus, in terms of impact on animal health, CVV is considered the most important. In humans, a diagnosis is rarely made, but survey blood samples indicate that exposure might be as high as 18% of the population in some areas.
A Canadian study showed widespread high exposure of domestic animals to CVV or closely related viruses in Saskatchewan. Only a few reports from around the world have been published, but limited comparisons show that the high seroprevalence in horses and moderate seroprevalence in cattle in that study are similar to results from other country’s investigations.
The virus infects kids and lambs in utero and leads to pregnancy failure and abortions of offspring with congenital malformations, if the infection occurs between 28- 48 days of gestation. This virus does not cause any clinical signs in the dam, however, which makes it difficult to identify presence of the virus in the herd.
Following a short viremic phase (brief fever, when the virus is circulating in the blood), the dam mounts an antibody response to the virus and clears it from her body.
Cache Valley, Akbane, Schmallenberg and Aino viruses belong to the genus Orthobunyavirus and all of them cause outbreaks of arthrogryposis, hydranencephaly and occasionally cerebellar hypoplasia (under-developed cerebrum) in calves and lambs. Cache Valley virus is more common in sheep, while Akbane and Aino viruses primarily affect cattle.
Other diseases can be mistaken for CVV. Fetal infection of calves and lambs with bovine virus diarrhea virus (BVD) or border disease virus (pestiviruses) often results in cerebellar hypoplasia, or, less commonly, hydranencephaly, porencephaly (cysts or cavities in brain tissue), hydrocephalus or ocular abnormalities.
Swine fever virus (also a pestivirus) infection can cause mummification, arthrogryposis and cerebellar hypoplasia in piglets. Infection with bluetongue virus (orbivirus) causes hydranencephaly and porencephaly in lambs and occasionally calves, but arthrogryposis is not a characteristic lesion in those diseases.
Wesselsbron virus (flavivirus) is associated with mummification, hydranencephaly, arthrogryposis, porencephaly and cerebellar hypoplasia in lambs and calves.
Testing of fetal tissues (including placenta and brain) can lead to isolation of the virus and proper diagnosis of the disease. Serologic analysis of dams (from blood samples) aids in detecting the seroprevalence of the virus in the herd, but does not confirm the disease in a fetus.
There is no vaccine to prevent this disease. The only prevention is control of mosquitoes and biting midges, which is difficult to accomplish.
There is no treatment for this disease.