As the competition season begins for many riders in the United States, it is particularly important to implement increased biosecurity measures against infectious disease. One of the more concerning outbreaks to control is that of equine herpesvirus myeloencephalopathy (EHM, or neurologic herpesvirus) caused by equine herpesvirus type 1 (EHV-1).
Usually horses are infected with herpesvirus at an early age, with estimates that 80-90% of the horse population has encountered herpes exposure before the age of 2. Herpes viral presence persists for the life of a horse following the initial infection. It is common for horses to be infected with both EHV-1 and EHV-4. However, EHV-4 is not associated with viremia, so there are rarely non-respiratory disease manifestations following EHV-4 infection.
Equine herpesvirus has been able to adapt within the horse host and thereby undergo a period of latency during which time an affected horse shows no clinical signs of infection, yet still can actively shed virus. EHV-1 is highly infectious and can be transmitted through fomites, aerosols, an aborted fetus or placental parts, or through direct horse-to-horse contact. Broodmares might provide continuous horizontal exposure from dam to foal, particularly if the virus underwent viral recrudescence from stress associated with pregnancy and foaling.
In horses, EHV-1 has the ability to infect many cell types: endothelial cells of inner organs, respiratory epithelial cells, and mononuclear cells in lymphoid organs and peripheral blood. Latent virus can “hide out” in lymphocytes and/or sensory nerve cell bodies within the trigeminal ganglia. Reactivation of virus—particularly during periods of stress—enables it to spread to susceptible horses through the respiratory tract. Not all “infected” horses show signs of illness; some are simply silent viral shedders.
With about 10 million horses living in the United States, this virus has the potential to create a huge economic impact on the equine industry. In its respiratory form, EHV-1 leads to fever, respiratory disease, and interrupted training and competition schedules. Silent shedders transmit virus to immunologically naive individuals. The virus also is known for its propensity to cause abortion in the last trimester. And of greatest concern is that it is responsible for outbreaks of severe neurologic disease—equine herpesvirus myeloencephalopathy or EHM—that are potentially fatal, or at the very least require quarantine of large groups of exposed horses. at quarantine interrupts training and competition schedules as well as travel.
Within one to three days of exposure, the virus replicates in respiratory epithelial cells—nasal and mucosal cells—to result in viral shedding. A sick horse displays nasal discharge, coughing, depression, anorexia, and at times enlargement of retropharyngeal lymph nodes. In some cases, particularly in foals, EHV-1 respiratory infection also creates ocular lesions of chorioretinitis or uveitis.
A horse previously exposed to, or immunized against, EHV-1 usually experiences less clinical severity of respiratory disease and for a shorter duration. Usually the respiratory form runs its course within a couple of weeks, although occasionally individuals can develop mild forms of equine asthma.
Experimental infection demonstrates that within 12 hours post-exposure, the virus is detected within the regional lymph nodes of the respiratory tract, likely due to interaction with the host immune system that triggers a response with inflammatory cytokines. While the cytokine response might be helpful to elicit an immune response programmed to eliminate viral antigen, it might also induce pro-inflammatory cytokines and activate coagulative responses that are counterproductive to defeating the consequences of infection.
From the upper respiratory tract, EHV-1 is able to invade more deeply into the tissues via infected monocytes. From there, it enters the reticuloendothelial system and the lymphatics to infect circulating leukocytes and endothelial cells of blood vessels. Once viremia develops, EHV-1 has the potential to enter the pregnant uterus or to invade the central nervous system to create myeloencephalopathy. Effects in the pregnant mare result in spontaneous abortion from endothelial cell invasion generally within nine to 13 days following infection or reactivation from latency.
EHV-1 is also able to cross the blood-testis barrier to be shed in semen for several weeks up to a month following viremia. Studies have identified monocytic-lymphocytic infiltrates and perivascular accumulations similar to those found with EHV-1-infected endometrial tissue and central nervous system tissues of EHM cases.
About 10% of EHV-1-infected horses develop equine herpesvirus myeloencephalopathy. When it occurs, it appears one to two weeks a er infection with or without respiratory signs. The vascular system of the central nervous system is affected through cell-associated viremia even if a horse has high levels of circulating antibodies.
The vascular endothelium might be damaged directly during viral replication and/or from immune complexes formed between EHV-1 and antibodies. These conditions lead to thrombo-ischemic necrosis of the microvasculature of the brain and central nervous system. It is reported that “there seems to be no satisfactory scientific explanation for the variable incidence of EHM and different clinical manifestations observed during outbreaks of EHV-1.”
Based on recent outbreaks, it is thought that a currently circulating neuropathogenic EHV-1 strain has evolved into a more pathogenic strain.
Current EHV-1 vaccines have no ability to combat EHM. An effective vaccine must have the ability to block cell-associated viremia to deter entry of virus in the uterus or central nervous system. The one thing that EHV-1 recombinant vaccines might accomplish is to reduce initial nasal viral shedding in vaccinates. One report recommended that the industry should “vaccinate every horse that is at risk of exposure to EHV-1 to help reduce the severity of EHV-1-related clinical manifestations.”
Animal Trust Herpes Vaccine Efforts
The Animal Health Trust in the United Kingdom is working to develop a vaccine that is protective against abortigenic and neurologic equine herpesvirus infection. Efforts to this end through an Equine Industries EHV Vaccine Steering Group will continue over the next four years, primarily investigating a modified live viral (MLV) vaccine.
Stakeholders in this steering group include experts on human and equine herpesvirus from around the world.
The Animal Health Trust researchers plan to construct up to seven different viruses with attenuating mutations to determine their appropriateness for use in a modified live viral vaccine.
References
Oladunni, F.S.; Horohov, D.W.; Chambers, T.M. EHV-1: A Constant Threat to the Horse Industry. Frontiers in Microbiology, Dec 2019, vol. 10, article 2668; doi: 10.3389/fmicb.2019.02668.
Hussey, G.S. Key Determinants in the Pathogenesis of Equine herpesvirus 1 and 4 Infections. Veterinary Pathology 2019, vol. 56, issue 5; pp. 656-659; DOI: 10.1177/0300985819849498.
Otzdorff, C.; Giebler, K.; Haupt, C.; Samoilowa, S., et al. EHV-1 Infection of the Equine Male Genital Tract. Journal of Equine Veterinary Science 2018, vol 66; p. 81.
