This is an excerpt from Equine Disease Quarterly, funded by underwriters at Lloyd’s, London, brokers, and their Kentucky agents.

Outbreaks of neurological disease caused by hypervirulent strains of EHV-1 have been reported with increasing and near-alarming frequency during the past several years (see the July 2003 issue of the Equine Disease Quarterly). This disease is characterized by high morbidity and case fatality rates, resistance to prevention by vaccination, and the ability to affect horses of all breeds, ages, and vaccination status. EHV-1 neurological disease has the potential for causing catastrophic losses to both the welfare of horses and the economy of equine-based businesses.

A major milestone in our understanding of the neurological form of EHV-1 infection recently has been achieved following a five-year, internationally collaborative research effort by scientists at the Maxwell H. Gluck Equine Research Center in the United States and the Animal Health Trust in the United Kingdom. With an eye toward identifying a genetic basis for the neuropathogenic phenotype of EHV-1, the DNA sequence of several key genes of the herpesvirus was determined for virus isolates collected from 48 outbreaks of EHV-1 neurological disease and 82 outbreaks of EHV-1 abortion without accompanying neurological involvement. The disease outbreaks occurred over a 35-year time span in eight different countries. An unanticipated outcome of the comparative genomics study was the finding of a single point mutation uniquely present in EHV-1 isolates from 83% of the neurological disease outbreaks and uniquely absent from 95% of EHV-1 abortion outbreaks. Importantly, the identified mutation that is highly associated (p<0.0001) with the capacity of an EHV-1 strain for causing neurologic signs in the horse is located in the catalytic subunit of the gene encoding the viral DNA polymerase. This discovery of a mutation-associated, monogenic determinant of EHV-1 neuropathogenicity has given rise to the hypothesis that underlying the pathogenetic basis of a neurologic EHV-1 strain is the acquired viral attribute of enhanced replicative aggressiveness made possible by a single, mutation-induced alteration of the enzymatic properties of its replicative polymerase. Recent empirical support of the hypothesis was provided by studies, supported by the Grayson-Jockey Club Research Foundation, Inc., demonstrating a fivefold greater level of virus delivered by viremic leukocytes to the blood vascular endothelium of the central nervous system of horses infected by paralytic strains of EHV-1 (Figure 1)