Equid gammaherpesvirus 2 and equid gammaherpesvirus 5 infections

Synonyms: Equid gammaherpesvirus infections, slowly cytopathic equid herpesvirus infections (formerly equid herpesvirus 2 and equid herpesvirus 5)

GENERAL INTRODUCTION: HERPESVIRIDAE

Introduction

Equid gammaherpesviruses are a genetically heterogeneous viral subfamily characterized by a narrow host range, slow replication, lymphotropism, and widespread distribution in horse populations. Their interactions with their host are not fully elucidated and have been the subject of continued interest and research. Importantly, their widespread distribution and obscure pathogenicity has been a significant challenge in establishing an association with specific clinical and pathological conditions and in defining their significance from a diagnostic standpoint.

The prototype LK strain of equid gammaherpesvirus 2 (EHV-2), the first gammaherpesvirus to be recovered from the horse, was isolated in 1962 from the respiratory mucus of a foal with ‘catarrh and coughing’.⁸⁰Since then, a great number of equid gammaherpesvirus isolates have been recovered from horses throughout the world.^{24, 27, 41, 48, 51, 56, 58, 90, 98, 101, 121} Twenty-five years elapsed before a subset of this large virus collection was recognized as sufficiently different to be classified as a second equid gammaherpesvirus type, equid gammaherpesvirus 5 (EHV-5).^{2, 20} To date, EHV-2 and EHV-5-associated infections are ubiquitous in horses around the globe. Characterized by extensive intratypic heterogeneity (both genetic and antigenic), a long replicative cycle, slow cell-to-cell viral infectivity, and low extracellular titres of infectious virus, the equid gammaherpesviruses comprise a complex and technically challenging group of herpesviruses for both equine virologists and practitioners.^{2, 3, 19, 21, 98}

A large proportion of the world’s horse population carries gammaherpesviruses as a life-long latent infection of circulating B lymphocytes as well as a fluctuating, persistent and productive infection of epithelial cells of the nasopharynx, conjunctiva and cornea.^{16, 21, 32, 40, 56, 64, 65, 90, 91, 110, 112, 121} These viruses are intermittently shed from these mucosal surfaces of infected horses, and infected mares effectively transmit the infection to foals soon after birth, even in the presence of colostrum-derived antibodies.^{12, 19, 45, 48, 70, 108, 121} Although of low inherent pathogenicity, EHV-2 has been associated with several significant, clinically overt equine diseases, including syndromes involving the of upper and lower respiratory tracts of foals, keratoconjunctivitis, chronic follicular pharyngitis, and malaise and poor performance syndrome in young performing horses.^{6, 14, 25, 26, 29, 37, 45, 48, 51, 55, 74, 75, 91, 99, 100, 102, 106, 107} In the case of EHV-5, this equid gammaherpesvirus has been associated with a specific condition known as equine multinodular pulmonary fibrosis (EMPF).^{122, 124}

Aetiology

Upon their original identification, EHV-2 and EHV-5 were recognized as ‘slowly cytopathic orphan herpesviruses’ of the domestic horse (Equus caballus)^{52, 72} and initially classified as equine cytomegalovirus-like betaherpesviruses within the subfamily Betaherpesvirinae.^{21, 41, 52, 94, 98, 115, 119} Equid gammaherpesvirus 2  and EHV-5 were indistinguishable from each other until the advent of restriction fragment length polymorphism analysis.¹⁰⁴ Subsequent sequence analysis of their genomic DNA led to their reclassification within the subfamily Gammaherpesvirinae, genus Rhadinovirus.^{3, 104, 116} Since 2008, both EHV-2 and EHV-5 have been classified within the subfamily Gammaherpesvirinae, genus Percavirus³¹ (Figure 1) along with other gammaherpesviruses recognized in cats, ferrets, seals and bats. The two gammaherpesviruses have been historically distinguished by differences in electrophoretic mobilities, DNA restriction endonuclease cleavage patterns, titres of homologous versus heterologous antisera for neutralizing the two viruses, and Southern blotting. Currently, these techniques have been replaced by next generation sequencing of full-length genomes, which provides unparalleled...