Equine Herpes Virus-1: An elusive target
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By Neil Bryant
Infectious diseases are not uncommon in racehorses in training, breeding stock, and pleasure horses. Some of the more serious diseases can be financially devastating to the animal’s owners and to the equine industry on the whole. Viruses belonging to the herpesvirus family cause some of the most well characterized equine infectious diseases, and the most problematic of these is equine herpesvirus 1 (EHV-1; species Equid alphaherpesvirus 1).
EHV-1 is ubiquitous in most horse populations in the world. It is responsible for major economic and welfare problems causing respiratory disease, neurological disease (mainly seen in adult horses), and abortion and neonatal foal death in pregnant mares. This was most notably highlighted by the multiple abortion outbreak recorded in Hertfordshire, England, between February and April 2016 in fully vaccinated animals (http://www.aht.org.uk/cms-display/interim-report16-april2.html). Studies have determined that EHV-1 is a common cause of abortion. Occasional cases have also been linked to EHV-4 infection, but this is much rarer and doesn’t account for episodes of multiple abortion, as is seen occasionally with EHV-1.
The virus
EHV-1 was first isolated from an equine abortion in the U.S. in the 1930s. At the time of first isolation the vets weren’t sure what it was, but they knew it was infectious. Subsequent genetic analysis much later led to the classification of the virus in the genus Varicellovirus (family Herpesviridae), together with its close relatives equine herpesvirus 4 (EHV-4; species Equid alphaherpesvirus 4) and equine herpesvirus 8 (EHV-8; species Equid alphaherpesvirus 8). Interestingly it is grouped with, and is therefore genetically similar to, the human herpesvirus responsible for chickenpox, the Varicella Zoster virus. Initial infection of horses was thought to occur around weaning, when virus-neutralizing antibodies transferred to the foal from the mare’s colostrum had declined enough to make them susceptible to infection. However, virus has been isolated from foals as young as seven days old with high antibody levels but without any significant clinical signs. Immunity to re-infection after primary infection is relatively short-lived, lasting between three-six months, but it is rare for naturally infected mares to abort in consecutive pregnancies.
Disease processes
The virus first enters the horses’ body via the respiratory tract, usually by direct contact with infected animals, contaminated surfaces, or equipment such as tack or veterinary instruments. Direct contact with infected aborted fetuses or placental tissues is also a major source of virus, which experience indicates can cause serious problems if they occur in open barns or large groups of horses.
Once the cells in the respiratory tract are infected, the virus spreads cell-to-cell until it finds its way to the regional lymph nodes, where it can infect white blood cells called lymphocytes. These lymphocytes circulate through the body carrying the virus with them, which is known as a “cell associated viraemia.” The infected lymphocytes can come into contact with and infect numerous cell types, including cells known as “endothelial cells,” which line the inside of blood vessels of the central nervous system and the pregnant uterus. With EHV-1 infection, these endothelial cells undergo an inflammatory response which can lead to bleeding, cell death, and blood clot formation, which in narrow veins disrupts blood supply. This process results in subsequent tissue damage and serious complications such as placental separation (occasionally with delivery of a virus-negative fetus) and/or leakage of virus across the separating placenta (most frequently with delivery of a virus-positive fetus).
Similar mechanisms play a role in neurological disease, a condition called equine herpesvirus myeloencephalopathy or EHM. This condition is also sometimes referred to as an equine stroke, as it is caused by the cellular inflammatory response rather than direct virus infection of nerve cells, which occurs with some other herpesviruses. Less serious clinical signs of infection can include fever, lethargy, inappetence, enlarged lymph nodes, and profuse clear nasal discharge, although not all infected animals will display clinical signs. Recently published work from the Irish Equine Centre has identified EHV-8 as also being occasionally responsible for abortions in mares. Cases of EHV-8 abortion have also been detected retrospectively by the Animal Health Trust (AHT) among its pathology caseload, as this virus, which is genetically almost identical to EHV-1, triggers positive results in the EHV-1 tests. The frequency and clinical relevance of EHV-8 at this stage is unclear. Of 100 viruses presumed to be EHV-1 and whose genetic material were recently analyzed by the AHT, three were actually confirmed as EHV-8.
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