Equine herpesvirus-1 is a highly prevalent and frequently pathogenic infection of equids. The most serious clinical consequences of infection are abortion and equine herpesvirus myeloencephalopathy (EHM). In recent years, there has been an apparent increase in the incidence of EHM in North America, with serious consequences for horses and the horse industry. This consensus statement draws together current knowledge in the areas of pathogenesis, strain variation, epidemiology, diagnostic testing, vaccination, outbreak prevention and control, and treatment.Key words: Abortion; Horse; Immunology; Infectious diseases; Myeloencephalopathy; Respiratory tract; Viral.E quine herpesvirus-1 (EHV-1) infection is ubiquitous in most horse populations throughout the world, and causes disease in horses and extensive economic losses through frequent outbreaks of respiratory disease, abortion, neonatal foal death, and myeloencephalopathy. [1][2][3][4] Infections caused by EHV-1 are particularly common in young performance horses, and typically result in establishment of latent infection within the 1st weeks or months of life 5 with subsequent viral reactivation causing clinical disease and viral shedding during periods of stress. The relevant effects of this virus on the equine population are 3-fold. Firstly, sporadic occurrence of mild respiratory disease associated with pyrexia, principally affecting horses under 2 years of age, can lead to interruptions in athletic training programs; this is economically the least important manifestation of EHV-1 disease. Secondly, abortion occurring during the 3rd trimester of pregnancy, results in important economic losses. Thirdly, outbreaks of neurological disease (equine herpes myeloencephalopathy or EHM) cause suffering and loss of life and also lead to extensive movement restrictions, disrupting breeding or training schedules and causing management difficulties at training centers, racetracks, and horse events. A perceived increase in the incidence of EHM outbreaks in North America in recent years has led to the proposal that it could represent an emerging disease threat. 6 The recent increased impact of EHM in North America provided the impetus for this consensus statement. The renewed focus on EHV-1 infection and its control, new developments in our understanding of this virus and its behavior in horses, and the development of new viral detection technologies have resulted in renewed challenges for clinicians in responding to the threat of EHV-1 and to outbreaks. In an attempt to address this challenge, this statement is structured as a series of critical questions, which we believe capture the key challenges for equine clinicians and scientists. The responses seek to distill current evidence-based knowledge Abbreviations:CTL cytotoxic T-lymphocyte EHM equine herpesvirus myeloencephalopathy EHV-1 equine herpesvirus-1 Consensus Statements of the American College of Veterinary Internal Medicine (ACVIM) provide the veterinary community with up-to-date information on the pathophysiolo...

Equid herpesvirus 1 (EHV-1) can cause a wide spectrum of diseases ranging from inapparent respiratory infection to the induction of abortion and, in extreme cases, neurological disease resulting in paralysis and ultimately death. It has been suggested that distinct strains of EHV-1 that differ in pathogenic capacity circulate in the field. In order to investigate this hypothesis, it was necessary to identify genetic markers that allow subgroups of related strains to be identified. We have determined all of the genetic differences between a neuropathogenic strain (Ab4) and a nonneuropathogenic strain (V592) of EHV-1 and developed PCR/ sequencing procedures enabling differentiation of EHV-1 strains circulating in the field. The results indicate the occurrence of several major genetic subgroups of EHV-1 among isolates recovered from outbreaks over the course of 30 years, consistent with the proposal that distinct strains of EHV-1 circulate in the field. Moreover, there is evidence that certain strain groups are geographically restricted, being recovered predominantly from outbreaks occurring in either North America or Europe. Significantly, variation of a single amino acid of the DNA polymerase is strongly associated with neurological versus nonneurological disease outbreaks. Strikingly, this variant amino acid occurs at a highly conserved position for herpesvirus DNA polymerases, suggesting an important functional role.Equid herpesvirus 1 (EHV-1), a member of the subfamily Alphaherpesvirinae, is a highly prevalent equine pathogen that can cause a range of clinical signs, from respiratory distress to the induction of abortion, neonatal foal death, and occasionally neurological damage resulting in paralysis (9,14,19,33,37,61). The severity of disease resulting from EHV-1 infection is likely to be influenced by a number of factors, including the age and physical condition of the host; whether the infection is primary, a reinfection, or a reactivation of latent virus; the immune status of the host; and the pathogenic potential of the strain involved. In order to assess the relative importance of EHV-1 strain variation regarding disease outcome, it is necessary to develop methods enabling precise discrimination between genetic subgroups of interrelated strains. Previous studies have utilized DNA restriction fragment length polymorphism (RFLP) to separate field isolates of EHV-1 into subgroups according to characteristic restriction enzyme site changes and the presence of variable numbers of copies of short sequence repeats. These studies demonstrated a relatively low frequency of genetic polymorphism for EHV-1 and suggested that distinct strains of EHV-1 do exist in the field (3,4,8,25,32,41,54,57). However, the relative lack of variation of EHV-1 sequences between strains has resulted in too few RFLP variants to be identified for detailed epidemiological studies. Furthermore, although such analyses may be used for tracing the genetic relatedness of strains, they allow identification only of those genetic changes resul...

No abstract

Infection with equid herpesvirus type 1 (EHV-1) leads to respiratory disease, abortion, and neurologic disorders in horses. Molecular epidemiology studies have demonstrated that a single nucleotide polymorphism resulting in an amino acid variation of the EHV-1 DNA polymerase (N752/D752) is significantly associated with the neuropathogenic potential of naturally occurring strains. To test the hypothesis that this single amino acid exchange by itself influences neuropathogenicity, we generated recombinant viruses with differing polymerase sequences. Here we show that the N752 mutant virus caused no neurologic signs in the natural host, while the D752 virus was able to cause inflammation of the central nervous system and ataxia. Neurologic disease induced by the D752 virus was concomitant with significantly increased levels of viremia (p = 0.01), but the magnitude of virus shedding from the nasal mucosa was similar between the N752 and D752 viruses. Both viruses replicated with similar kinetics in fibroblasts and epithelial cells, but exhibited differences in leukocyte tropism. Last, we observed a significant increase (p < 0.001) in sensitivity of the N752 mutant to aphidicolin, a drug targeting the viral polymerase. Our results demonstrate that a single amino acid variation in a herpesvirus enzyme can influence neuropathogenic potential without having a major effect on virus shedding from infected animals, which is important for horizontal spread in a population. This observation is very interesting from an evolutionary standpoint and is consistent with data indicating that the N752 DNA pol genotype is predominant in the EHV-1 population, suggesting that decreased viral pathogenicity in the natural host might not be at the expense of less efficient inter-individual transmission.

Herpesviruses, such as murine and human cytomegalovirus (MCMV and HCMV), can establish a persistent infection within the host and have diverse mechanisms as protection from host immune defences. Several herpesvirus genes that are homologous to host immune modulators have been identified, and are implicated in viral evasion of the host immune response. The discovery of a viral major histocompatibility complex (MHC) class I homologue, encoded by HCMV, led to speculation that it might function as an immune modulator and disrupt presentation of peptides by MHC class I to cytotoxic T cells. However, there is no evidence concerning the biological significance of this gene during viral infection. Recent analysis of the MCMV genome has also demonstrated the presence of a MHC class I homologue. Here we show that a recombinant MCMV, in which the gene encoding the class I homologue has been disrupted, has severely restricted replication during the acute stage of infection compared with wild-type MCMV. We demonstrate by in vivo depletion studies that natural killer (NK) cells are responsible for the attenuated phenotype of the mutant. Thus the viral MHC class I homologue contributes to immune evasion through interference with NK cell-mediated clearance.