Equine myeloencephalopathy (EHM), an uncommon manifestation of equine herpesvirus 1 (EHV-1) infection, can cause devastating losses on individual farms, boarding stables, veterinary hospitals, and show and racing venues. An improved understanding of EHM has emerged from experimental studies and from data collected during field outbreaks at riding schools, racetracks, horse shows, and veterinary hospitals throughout North America and Europe. These outbreaks have highlighted the contagious nature of EHV-1 and have prompted a reevaluation of diagnostic procedures, treatment modalities, preventative measures, and biosecurity protocols for this disease. This article focuses on recent data related to the cause, epidemiology, pathogenesis, immunity, diagnosis, treatment, and prevention of EHV-1 infection with emphasis on EHM.

Keywords

Equine herpesvirus 1

Equine herpesvirus myeloencephalopathy

Etiology

Epidemiology

Pathogenesis

Clinical signs

Diagnosis

Treatment

Key points

Introduction

Equine herpesvirus 1 (EHV-1) myeloencephalopathy (EHM), although a relatively uncommon manifestation of EHV-1 infection, can cause devastating losses on individual farms, boarding stables, veterinary hospitals, and show and racing venues. Although outbreaks of EHM have been recognized for centuries in domestic horse populations, many aspects of this disease remain poorly characterized. In recent years, an improved understanding of EHM has emerged from experimental studies and from data collected during field outbreaks at riding schools, racetracks, horse shows, and veterinary hospitals throughout North America and Europe. These outbreaks have highlighted the contagious nature of EHV-1 and have prompted a reevaluation of diagnostic procedures, treatment modalities, preventative measures, and biosecurity protocols for this disease. This article focuses on the recent data related to the cause, epidemiology, pathogenesis, immunity, diagnosis, treatment, and prevention of EHV-1 infection with emphasis on EHM.

Etiology

EHV-1 is an important, ubiquitous equine viral pathogen that exerts its major impact by inducing abortion storms or sporadic abortions in pregnant mares, early neonatal death in foals, respiratory disease in young horses, and myeloencephalopathy.1 Although EHM is a sporadic and relatively uncommon manifestation of EHV-1 infection, it can cause devastating losses and severely impact the equine industry, as exemplified by recent outbreaks at riding schools, racetracks, horse shows, and veterinary hospitals throughout North America and Europe.2–4

EHV-1 and EHV-4 are α-herpesviruses and are distinguishable from EHV-2, EHV-3, and EHV-5 by biologic properties and virus neutralization tests, and from each other by restriction endonuclease fingerprinting of DNA, DNA sequences, and several immunologic tests based on monoclonal antibodies to each virus.1,5,6 EHV-1 and EHV-4 are closely related but genetically and antigenically different and associated with distinct disease profiles.

EHV-1 is a DNA virus that possesses linear double-stranded genomes composed of a unique long region, joined to a unique short region that is flanked by an identical pair of inverted repeat regions, the terminal repeat and the internal repeat regions.7 The EHV-1 genome is 150 kilobases in size and encodes for 76 open reading frames or genes. Expression of these genes within infected cells is tightly ordered into a highly controlled cascade.8 One complete replication cycle takes approximately 20 hours during which well-ordered sequential events occur, including attachment to the host cell membrane, membrane fusion and penetration, translocation of viral DNA to the nucleus, viral DNA replication and protein synthesis, assembly of the capsid, envelopment, and lysis of the cell with release of progeny virions.

Virulence markers distinguishing EHV-1 strains that induce EHM and/or abortion have recently been determined. The most important discovery may be the association with a single nucleotide polymorphism at position 2254 in the DNA polymerase gene (ORF 30) and the occurrence of EHM.9 Analysis of more than 100 EHV-1 outbreaks with various clinical presentations demonstrated that variability of a single amino acid residue at position 752 of the DNA polymerase was found to be strongly associated with the occurrence of EHM, with EHV-1 strains associated with neurologic outbreaks involving a D752 genotype, whereas most nonneurologic outbreaks involved a N752 genotype.9,10 The observation that EHV-1 viruses of the D752 genotype have a greater potential to induce EHM was recently supported by an experimental study using recombinant viruses with differing polymerase sequences.11 The N752 mutant virus caused no neurologic signs and was associated with reduced levels of viremia, whereas viral shedding was similar between both virus mutants. From an epidemiologic standpoint it seems that most EHV-1 viruses circulating in the field are of the N752 genotype.12,13 Although EHV-1 D752 genotype viruses are more commonly associated with EHM, viruses with a N752 genotype are certainly not apathogenic; they have been responsible for approximately 81% to 98% of abortion outbreaks in the United States, United Kingdom, and other countries, and between 15% and 26% of neurologic outbreaks (Fig. 1).

Epidemiology

According to Allen and colleagues14 the main epidemiologically relevant features of EHV-1 include high incidence of respiratory infection early in life; establishment of latency in a high percentage of infected horses; and frequent reactivation of latent virus with subsequent shedding, resulting in transmission to naive hosts. Currently, it is estimated that 80% of all horses are latently infected; however, prevalence may vary depending on geographic region and age.15 Furthermore, testing technology and tissues sampled for detection of latency affect sensitivity of testing and actual numbers of latently infected horses may be even higher.12,13

Primary infection of the...