Equid herpesvirus 1 and equid herpesvirus 4 infections

G P ALLEN, J H KYDD, J D SLATER AND K C SMITH

GENERAL INTRODUCTION: HERPESVIRIDAE

Introduction

Equid herpesvirus 1 (EHV-1) and equid herpesvirus 4 (EHV-4) are ubiquitous herpesviruses that infect the majority of the world’s domestic horses (Equus caballus) at some time during their lives, frequently resulting in serious clinical illness.^{5, 43, 44, 73, 74, 162, 174} Infections by the two herpesviruses have been recognized for over 60 years as significant and worldwide impediments to the breeding, competition and recreational horse industries.^{49, 82, 83, 85, 86, 87, 116, 125, 128, 129, 153, 160, 166, 167, 170, 182, 197, 233, 254}The economic losses and negative impact on equine welfare caused by EHV-1 and EHV-4 occur perennially, are cumulatively immense, and are the result of morbidity or mortality from virus-induced abortion, respiratory disease, neurological disorders, or death of full-term and new-born foals.

Since the discovery of this viscerotropic subgroup of alphaherpesviruses of the horse (Table 76.1), major advances have been achieved in characterizing their physicochemical and molecular properties and in understanding the natural history of the virus–host relationship. Like all members of the Herpesviridae family of viruses, EHV-1 and EHV-4 are phylogenetically ancient and, during their protracted co-evolution with the horse, have become extremely successful viral parasites. Such success of EHV-1 and EHV-4 as permanent guests of the horse is dependent upon the possession, by the two herpesviruses, of a combination of unique biological features:

• tropism for equine respiratory mucosal epithelium that permits efficient viral entry into the horse;
• post-infection persistence of the viruses in a non-replicating, latent form in a long-lived set of equine cells to create a large, permanent reservoir of the viruses;
• virological attributes that provide a mechanism for re-emergence from their latent, cellular repository to the equine respiratory tract with shedding of infectious virions into the respiratory secretions; and 
• a variety of evasive immunological mechanisms, such as latency, immunosuppression and direct cell-to-cell transfer of virus, for circumventing host antiviral defences.

From a biological viewpoint, the pathogenic potential of EHV-1 and EHV-4 for the horse and the resulting negative economic and welfare impact on equine activities can be considered as consequences of basic herpesviral attributes that, over eons of time, have been evolutionarily acquired for ensuring long-term survival of the viruses as microparasites of horses.

Aetiology

General properties of EHV-1 and EHV-4

Equid herpesvirus 1 and EHV-4 are members of the Alphaherpesvirinae subfamily of herpesviruses of the domestic horse and are now included in the genus Varicellovirus, together with several other alphaherpesviruses of veterinary importance (e.g. bovine herpesvirus 1 and 5, caprine herpesvirus 1, equid herpesvirus 3, felid herpesvirus 1 and suid herpesvirus 1).^{78, 196} Their size, virion architecture, and overall replicative strategy are similar to those shared by all herpesviruses. Equid herpesvirus 1 and EHV-4 are closely related to one another but are antigenically, genetically, and pathogenetically distinct from equid herpesvirus 2 (EHV-2), EHV-3, and EHV- 5.^{8, 20, 73, 127, 218} They share no neutralizing or protective epitopes and only minor genetic homology with these three other herpesviruses of horses.^{184, 185, 250}

Equid herpesvirus 1 and EHV-4 are environmentally labile, and infectivity is quickly destroyed by lipid solvents, detergents, heat, and the common disinfectants available for veterinary use.⁹⁴ Virus survival outside of the horse is generally thought to be of short duration, although the extracorporal viability of EHV-1 at ambient temperature has been experimentally demonstrated to be as long as seven days when dried on paper, wood or rope, and 35 days on burlap or horsehair.⁹⁴

Table 76.1 Known herpesviruses of Equidae

^a Viruses located in the same horizontal row of the table represent closely related equid herpesviruses exhibiting minor genetic and antigenic divergence induced by natural adaptation of a common progenitor to different equid species

^b Virus names in parentheses are genus designations assigned by the Herpesvirus Study Group of the International Committee on Taxonomy and Nomenclature of Viruses (ICTV).^{78, 196} No ICTV designations have at this date been assigned by the Study Group to the zebra or onager herpesviruses⁷⁸ A neurotropic herpesvirus isolate from captive gazelle closely related to equid herpesvirus 1 has provisionally been designated equid...