Alpha-herpesviruses are a worldwide problem, causing upper respiratory tract disease, abortion, neonatal death, and chorioretinopathy of the eye. Herpes-related neurologic disease (equine herpes myeloencephalopathy aka EHM) occurs in 10% of those infected with EHV-1 and has a huge economic impact as well as high sickness rates and mortality.
Gisela Soboll Hussey, DVM, MS, PhD of Michigan State University discussed some salient facts about equine herpesvirus (EHV-1) pathogenesis and potentials for control. She describes how the virus is inhaled into the upper respiratory tract where it replicates in the epithelium, passes into local lymphocytes and lymphoid tissue to cause cell-associated viremia. Then it infects vascular endothelia (cells lining blood and lymphatic vessels) of secondary sites of the uterus or spinal cord. This leads to white blood cell infiltration with thrombosis and tissue destruction to cause secondary disease manifestations.
A mutation in a gene of the virus occurs in paralytic and abortigenic strains with both able to cause equine herpes myeloencephalopathy (EHM). Other risk factors include age, gender, stress, breed, and presence of pregnancy. Horses younger than 15 years of age develop EHM at an incidence of <10% while horses older than 20 years of age have a 50-70% risk. It is possible that younger immune systems may be more capable of controlling EHM.
To study this supposition, a study compared young and old horses infected with a neuropathogenic strain of EHV-1 with the objective of identifying host factors that amplify the risk of infection. Nine young horses around two years of age and 10 old horses were included in the study. Following infection, the young horses exhibited the classic biphasic fever response during both the onset of respiratory disease and then the later onset of viremia. Fever only developed in the older horses during the onset of viremia.
The young horses had significant respiratory disease while the older horses did not. Young horses shed more nasal virus while the older horses had higher viremic levels. EHM signs occurred in 9 of 10 older horses and six had to be euthanized; EHM signs occurred in only 1 of the 9 young horses, and that horse recovered spontaneously.
Immune responses varied at different sites of infection that foretold the outcome of which horses might develop EHM. The younger, protected horses produced interferon and a specific interleukin 17 early on in days 1-2 post-infection. In contrast, the EHM-affected older horses secrete interleukin Il-10 early on but not much interferon in either the respiratory tract or the central nervous system. This type of interleukin response and lack of interferon alters the body’s response to stimulate immune-acting T-cells. EHM-affected horses developed a TH2-adaptive immunity rather than a TH1-adaptive immunity. There was no difference in viral neutralizing antibodies (that protect against viral shedding) between control horses and those affected with EHM.
Next steps may be to consider methods to change the early immune events at the respiratory tract since early responses in the respiratory tract shape what happens later on with adaptive immunity. If it is possible to shift to a greater interferon response in the respiratory tract, a horse then may develop a TH1- adaptive response to prevent neurologic disease. Adjuvants or supplements may help to alter respiratory immunity, or perhaps there is a potential for viral gene modulation, says Hussey. Based on the study’s results, it may be practical to use middle-aged or older horses for evaluation of vaccine efficacy.
To date, without any currently available vaccine products for EHM, control is limited to biosecurity measures, which are the cornerstone of protection and prevention. Transmission is most accomplished with contact and less so with aerosol spread, she says. An infected horse should be isolated for 28 days after the last new infection. Personnel and equipment should be dedicated to only care for an infected horse, and small animals should be kept away as they can spread disease across a facility.